Heme oxygenase and the immune system in normal and pathological pregnancies

Frontiers in Pharmacology

Volumn 6, Issue APR, 2015, Pages

  Ozen, Maide ^a   Zhao, Hui ^a   Lewis, David B ^a   Wong, Ronald J ^a   Stevenson, David K ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Fetus; HO 1; Immunomodulation; Immunotolerance; Newborn; Placenta; Pregnancy

Indexed keywords

ACETYLSALICYLIC ACID; CARBON MONOXIDE; HEME OXYGENASE 1; HYPOXIA INDUCIBLE FACTOR 1ALPHA; PRAVASTATIN; SCATTER FACTOR; SIMVASTATIN;

ABORTION; ALLOGRAFT; BLOOD; CHORIOAMNIONITIS; DECIDUA; FEMALE INFERTILITY; FETAL INFLAMMATORY RESPONSE SYNDROME; FUNISITIS; GENE EXPRESSION; HOST; HUMAN; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; IMMUNOTHERAPY; MESENCHYMAL STROMA CELL; NONHUMAN; PERINATAL INFECTION; PLACENTA; PREECLAMPSIA; PREGNANCY; PREGNANCY DISORDER; PREGNANCY OUTCOME; PREMATURE FETUS MEMBRANE RUPTURE; PREMATURE LABOR; REPRODUCTION; REVIEW; SPONTANEOUS ABORTION;

EID: 84930668890     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2015.00084     Document Type: Review

References (131)

1. Acevedo, C. H., and Ahmed, A. (1998). Hemeoxygenase-1 inhibits human myometrial contractility via carbon monoxide and is upregulated by progesterone during pregnancy. J. Clin. Invest. 101, 949-955. doi: 10.1172/JCI927.
2. Ahmed, A. (2011). New insights into the etiology of preeclampsia: identification of key elusive factors for the vascular complications. Thromb. Res. 127(Suppl. 3), S72-S75. doi: 10.1016/S0049-3848(11)70020-2.
3. Amano, M. T., and Camara, N. O. (2013). The immunomodulatory role of carbon monoxide during transplantation. Med. Gas Res. 3, 1. doi: 10.1186/2045-9912-3-1.
4. Ambegaokar, S. S., and Kolson, D. L. (2014). Heme oxygenase-1 dysregulation in the brain: implications for HIV-associated neurocognitive disorders. Curr. HIV Res. 12, 174-188. doi: 10.2174/1570162X12666140526122709.
5. Anderson, U. D., Olsson, M. G., Kristensen, K. H., Akerstrom, B., and Hansson, S. R. (2012). Review: biochemical markers to predict preeclampsia. Placenta 33(Suppl.), S42-S47. doi: 10.1016/j.placenta.2011.11.021.
6. Arck, P. C., and Hecher, K. (2013). Fetomaternal immune cross-talk and its consequences for maternal and offspring's health. Nat. Med. 19, 548-556. doi: 10.1038/nm.3160.
7. Bartkeviciene, D., Pilypiene, I., Drasutiene, G., Bausyte, R., Mauricas, M., Silkunas, M., et al. (2013). Leukocytosis as a prognostic marker in the development of fetal inflammatory response syndrome. Libyan J. Med. 8, 21674. doi: 10.3402/ljm.v8i0.21674.
8. Ben Amara, A., Gorvel, L., Baulan, K., Derain-Court, J., Buffat, C., Verollet, C., et al. (2013). Placental macrophages are impaired in chorioamnionitis, an infectious pathology of the placenta. J. Immunol. 191, 5501-5514. doi: 10.4049/jimmunol.1300988.
9. + regulatory T cells. Proc. Natl. Acad. Sci. U.S.A. 107, 6424-6429. doi: 10.1073/pnas.0912437107.
10. Bharucha, A. E., Choi, K. M., Saw, J. J., Gibbons, S. J., Farrugia, G. F., Carlson, D. A., et al. (2014). Effects of aspirin & simvastatin and aspirin, simvastatin, & lipoic acid on heme oxygenase-1 in healthy human subjects. Neurogastroenterol. Motil. 26, 1437-1442. doi: 10.1111/nmo.12404.
11. + T cells is not sufficient for their development of immunoregulatory capacity. J. Leukoc. Biol. 87, 193-202. doi: 10.1189/jlb.0508280.
12. Brouard, S., Otterbein, L. E., Anrather, J., Tobiasch, E., Bach, F. H., Choi, A. M., et al. (2000). Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. J. Exp. Med. 192, 1015-1026. doi: 10.1084/jem.192.7.1015.
13. Bunse, C. E., Fortmeier, V., Tischer, S., Zilian, E., Figueiredo, C., Witte, T., et al. (2014). Modulation of heme oxygenase-1 by metalloporphyrins increases antiviral T-cell responses. Clin. Exp. Immunol. 179, 265-276. doi: 10.1111/cei.12451.
14. Burd, I., Balakrishnan, B., and Kannan, S. (2012). Models of fetal brain injury, intrauterine inflammation, and preterm birth. Am. J. Reprod. Immunol. 67, 287-294. doi: 10.1111/j.1600-0897.2012.01110.x.
15. Burt, T. D., Seu, L., Mold, J. E., Kappas, A., and McCune, J. M. (2010). Naive human T cells are activated and proliferate in response to the heme oxygenase-1 inhibitor tin mesoporphyrin. J. Immunol. 185, 5279-5288. doi: 10.4049/jimmunol.0903127.
16. Caliendo, L. (2007). [Comparison between lymphocytic infiltration in early spontaneous abortions and in elective abortions with signs of disruption at the chorio-decidual interface]. Minerva Ginecol. 59, 585-589.
17. Cantu, J. A., Jauk, V. R., Owen, J., Biggio, J. R., Abramovici, A. R., Edwards, R. K., et al. (2015). Is low-dose aspirin therapy to prevent preeclampsia more efficacious in non-obese women or when initiated early in pregnancy? J. Matern. Fetal Neonatal. Med. 8, 1-5. doi: 10.3109/14767058.2014.947258.
18. Capece, A., Vasieva, O., Meher, S., Alfirevic, Z., and Alfirevic, A. (2014). Pathway analysis of genetic factors associated with spontaneous preterm birth and pre-labor preterm rupture of membranes. PLoS ONE 9:e108578. doi: 10.1371/journal.pone.0108578.
19. Carpentier, P. A., Dingman, A. L., and Palmer, T. D. (2011). Placental TNF-a signaling in illness-induced complications of pregnancy. Am. J. Pathol. 178, 2802-2810. doi: 10.1016/j.ajpath.2011.02.042.
20. Cerdeira, A. S., Kopcow, H. D., and Karumanchi, S. A. (2012). Regulatory T cells in preeclampsia: some answers, more questions? Am. J. Pathol. 181, 1900-1902. doi: 10.1016/j.ajpath.2012.09.020.
21. Chen, J. C., Huang, K. C., and Lin, W. W. (2006). HMG-CoA reductase inhibitors upregulate heme oxygenase-1 expression in murine RAW264.7 macrophages via ERK, p38 MAPK and protein kinase G pathways. Cell. Signal. 18, 32-39. doi: 10.1016/j.cellsig.2005.03.016.
22. Costantine, M. M., Cleary, K., and Eunice Kennedy Shriver National Institute of Child Health and Human Development Obstetric-Fetal Pharmacology Research Units Network. (2013). Pravastatin for the prevention of preeclampsia in high-risk pregnant women. Obstet. Gynecol. 121, 349-353.
23. Croxatto, D., Vacca, P., Canegallo, F., Conte, R., Venturini, P. L., Moretta, L., et al. (2014). Stromal cells from human decidua exert a strong inhibitory effect on NK cell function and dendritic cell differentiation. PLoS ONE 9:e89006. doi: 10.1371/journal.pone.0089006.
24. reg balance by hypoxia-inducible factor 1. Cell 146, 772-784. doi: 10.1016/j.cell.2011.07.033.
25. de Jong, P. G., Kaandorp, S., Di Nisio, M., Goddijn, M., and Middeldorp, S. (2014). Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia. Cochrane Database Syst. Rev. 7, CD004734. doi: 10.1002/14651858.CD004734.pub4.
26. Della Bella, S., Giannelli, S., Cozzi, V., Signorelli, V., Cappelletti, M., Cetin, I., et al. (2011). Incomplete activation of peripheral blood dendritic cells during healthy human pregnancy. Clin. Exp. Immunol. 164, 180-192. doi: 10.1111/j.1365-2249.2011.04330.x.
27. Denschlag, D., Marculescu, R., Unfried, G., Hefler, L. A., Exner, M., Hashemi, A., et al. (2004). The size of a microsatellite polymorphism of the haem oxygenase 1 gene is associated with idiopathic recurrent miscarriage. Mol. Hum. Reprod. 10, 211-214. doi: 10.1093/molehr/gah024.
28. Dentali, F., Ageno, W., Rezoagli, E., Rancan, E., Squizzato, A., Middeldorp, S., et al. (2012). Low-dose aspirin for in vitro fertilization or intracytoplasmic sperm injection: a systematic review and a meta-analysis of the literature. J. Thromb. Haemost. 10, 2075-2085. doi: 10.1111/j.1538-7836.2012.04886.x.
29. De Wilde, V., Van Rompaey, N., Hill, M., Lebrun, J. F., Lemaitre, P., Lhomme, F., et al. (2009). Endotoxin-induced myeloid-derived suppressor cells inhibit alloimmune responses via heme oxygenase-1. Am. J. Transplant. 9, 2034-2047. doi: 10.1111/j.1600-6143.2009.02757.x.
30. Diamond, A. K., Sweet, L. M., Oppenheimer, K. H., Bradley, D. F., and Phillippe, M. (2007). Modulation of monocyte chemotactic protein-1 expression during lipopolysaccharide-induced preterm delivery in the pregnant mouse. Reprod. Sci. 14, 548-559. doi: 10.1177/1933719107307792.
31. - regulatory T-cell populations are enriched in human early normal pregnancy decidua: a phenotypic study of paired decidual and peripheral blood samples. Am. J. Reprod. Immunol. 66(Suppl. 1), 44-56. doi: 10.1111/j.1600-0897.2011.01046.x.
32. Dorresteijn, M. J., Paine, A., Zilian, E., Fenten, M. G., Frenzel, E., Janciauskiene, S., et al. (2015). Cell-type-specific downregulation of heme oxygenase-1 by lipopolysaccharide via Bach1 in primary human mononuclear cells. Free Radic. Biol. Med. 78, 224-232. doi: 10.1016/j.freeradbiomed.2014.10.579.
33. El-Mousleh, T., Casalis, P. A., Wollenberg, I., Zenclussen, M. L., Volk, H. D., Langwisch, S., et al. (2012). Exploring the potential of low doses carbon monoxide as therapy in pregnancy complications. Med. Gas Res. 2, 4. doi: 10.1186/2045-9912-2-4.
34. Faas, M. M., Spaans, F., and De Vos, P. (2014). Monocytes and macrophages in pregnancy and pre-eclampsia. Front. Immunol. 5:298. doi: 10.3389/fimmu.2014.00298.
35. Fu, B., Tian, Z., and Wei, H. (2014). TH17 cells in human recurrent pregnancy loss and pre-eclampsia. Cell. Mol. Immunol. 11, 564-570. doi: 10.1038/cmi.2014.54.
36. Gendron, R. L., Nestel, F. P., Lapp, W. S., and Baines, M. G. (1990). Lipopolysaccharide-induced fetal resorption in mice is associated with the intrauterine production of tumour necrosis factor-alpha. J. Reprod. Fertil. 90, 395-402. doi: 10.1530/jrf.0.0900395.
37. + regulatory T cells is dependent on expression of heme oxygenase-1 in antigen-presenting cells. Am. J. Pathol. 173, 154-160. doi: 10.2353/ajpath.2008.070963.
38. Gervasi, M. T., Chaiworapongsa, T., Naccasha, N., Blackwell, S., Yoon, B. H., Maymon, E., et al. (2001). Phenotypic and metabolic characteristics of maternal monocytes and granulocytes in preterm labor with intact membranes. Am. J. Obstet. Gynecol. 185, 1124-1129. doi: 10.1067/mob.2001.117681.
39. Gill, A. J., Kovacsics, C. E., Cross, S. A., Vance, P. J., Kolson, L. L., Jordan-Sciutto, K. L., et al. (2014). Heme oxygenase-1 deficiency accompanies neuropathogenesis of HIV-associated neurocognitive disorders. J. Clin. Invest. 124, 4459-4472. doi: 10.1172/JCI72279.
40. Gonzalez, J. M., Pedroni, S. M., and Girardi, G. (2014). Statins prevent cervical remodeling, myometrial contractions and preterm labor through a mechanism that involves hemoxygenase-1 and complement inhibition. Mol. Hum. Reprod. 20, 579-589. doi: 10.1093/molehr/gau019.
41. Grosser, N., Abate, A., Oberle, S., Vreman, H. J., Dennery, P. A., Becker, J. C., et al. (2003). Heme oxygenase-1 induction may explain the antioxidant profile of aspirin. Biochem. Biophys. Res. Commun. 308, 956-960. doi: 10.1016/S0006-291X(03)01504-3.
42. Guerin, L. R., Prins, J. R., and Robertson, S. A. (2009). Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? Hum. Reprod. Update 15, 517-535. doi: 10.1093/humupd/dmp004.
43. Haga, Y., Tempero, M. A., Kay, D., and Zetterman, R. K. (1996). Intracellular accumulation of unconjugated bilirubin inhibits phytohemagglutin-induced proliferation and interleukin-2 production of human lymphocytes. Dig. Dis. Sci. 41, 1468-1474. doi: 10.1007/BF02088574.
44. Halgunset, J., Johnsen, H., Kjollesdal, A. M., Qvigstad, E., Espevik, T., and Austgulen, R. (1994). Cytokine levels in amniotic fluid and inflammatory changes in the placenta from normal deliveries at term. Eur. J. Obstet. Gynecol. Reprod. Biol. 56, 153-160. doi: 10.1016/0028-2243(94)90162-7.
45. Hinkelmann, U., Grosser, N., Erdmann, K., Schroder, H., and Immenschuh, S. (2010). Simvastatin-dependent up-regulation of heme oxygenase-1 via mRNA stabilization in human endothelial cells. Eur. J. Pharm. Sci. 41, 118-124. doi: 10.1016/j.ejps.2010.05.021.
46. Hirashima, M., Lu, Y., Byers, L., and Rossant, J. (2003). Trophoblast expression of fms-like tyrosine kinase 1 is not required for the establishment of the maternal-fetal interface in the mouse placenta. Proc. Natl. Acad. Sci. U.S.A. 100, 15637-15642. doi: 10.1073/pnas.2635424100.
47. Houser, B. L. (2012). Decidual macrophages and their roles at the maternal-fetal interface. Yale J. Biol. Med. 85, 105-118.
48. Hsu, M., Muchova, L., Morioka, I., Wong, R. J., Schroder, H., and Stevenson, D. K. (2006). Tissue-specific effects of statins on the expression of heme oxygenase-1 in vivo. Biochem. Biophys. Res. Commun. 343, 738-744. doi: 10.1016/j.bbrc.2006.03.036.
49. Imanirad, P., Solaimani Kartalaei, P., Crisan, M., Vink, C., Yamada-Inagawa, T., de Pater, E., et al. (2014). HIF1a is a regulator of hematopoietic progenitor and stem cell development in hypoxic sites of the mouse embryo. Stem Cell Res. 12, 24-35. doi: 10.1016/j.scr.2013.09.006.
50. Jeanty, C., Derderian, S. C., and Mackenzie, T. C. (2014). Maternal-fetal cellular trafficking: clinical implications and consequences. Curr. Opin. Pediatr. 26, 377-382. doi: 10.1097/MOP.0000000000000087.
51. Kaartokallio, T., Klemetti, M. M., Timonen, A., Uotila, J., Heinonen, S., Kajantie, E., et al. (2014). Microsatellite polymorphism in the heme oxygenase-1 promoter is associated with nonsevere and late-onset preeclampsia. Hypertension 64, 172-177. doi: 10.1161/HYPERTENSIONAHA.114.03337.
52. Kahlo, K., Fill Malfertheiner, S., Ignatov, T., Jensen, F., Costa, S. D., Schumacher, A., et al. (2013). HO-1 as modulator of the innate immune response in pregnancy. Am. J. Reprod. Immunol. 70, 24-30. doi: 10.1111/aji.12115.
53. Kamoi, M., Fukui, A., Kwak-Kim, J., Fuchinoue, K., Funamizu, A., Chiba, H., et al. (2015). NK22 cells in the uterine mid-secretory endometrium and peripheral blood of women with recurrent pregnancy loss and unexplained infertility. Am. J. Reprod. Immunol. doi: 10.1111/aji.12356 [Epub ahead of print].
54. + regulatory T cells in pregnant women with recurrent pregnancy loss. Am. J. Reprod. Immunol. 71, 441-450. doi: 10.1111/aji.12208.
55. Kim, S. K., Romero, R., Chaiworapongsa, T., Kusanovic, J. P., Mazaki-Tovi, S., Mittal, P., et al. (2009). Evidence of changes in the immunophenotype and metabolic characteristics (intracellular reactive oxygen radicals) of fetal, but not maternal, monocytes and granulocytes in the fetal inflammatory response syndrome. J. Perinat. Med. 37, 543-552. doi: 10.1515/JPM.2009.106.
56. Koliaraki, V., and Kollias, G. (2011). A new role for myeloid HO-1 in the innate to adaptive crosstalk and immune homeostasis. Adv. Exp. Med. Biol. 780, 101-111. doi: 10.1007/978-1-4419-5632-3_9.
57. Kostlin, N., Kugel, H., Spring, B., Leiber, A., Marme, A., Henes, M., et al. (2014). Granulocytic myeloid derived suppressor cells expand in human pregnancy and modulate T-cell responses. Eur. J. Immunol. 44, 2582-2591. doi: 10.1002/eji.201344200.
58. Lambers, M. J., Hoozemans, D. A., Schats, R., Homburg, R., Lambalk, C. B., and Hompes, P. G. (2009). Low-dose aspirin in non-tubal IVF patients with previous failed conception: a prospective randomized double-blind placebo-controlled trial. Fertil. Steril. 92, 923-929. doi: 10.1016/j.fertnstert.2008.07.1759.
59. Lash, G. E., and Bulmer, J. N. (2011). Do uterine natural killer (uNK) cells contribute to female reproductive disorders? J. Reprod. Immunol. 88, 156-164. doi: 10.1016/j.jri.2011.01.003.
60. Le Bouteiller, P. (2013). Human decidual NK cells: unique and tightly regulated effector functions in healthy and pathogen-infected pregnancies. Front. Immunol. 4:404. doi: 10.3389/fimmu.2013.00404.
61. Linzke, N., Schumacher, A., Woidacki, K., Croy, B. A., and Zenclussen, A. C. (2014). Carbon monoxide promotes proliferation of uterine natural killer cells and remodeling of spiral arteries in pregnant hypertensive heme oxygenase-1 mutant mice. Hypertension 63, 580-588. doi: 10.1161/HYPERTENSIONAHA.113.02403.
62. Liu, F., Guo, J., Tian, T., Wang, H., Dong, F., Huang, H., et al. (2011). Placental trophoblasts shifted Th1/Th2 balance toward Th2 and inhibited Th17 immunity at fetomaternal interface. APMIS 119, 597-604. doi: 10.1111/j.1600-0463.2011.02774.x.
63. McCoubrey, W. K. Jr., Huang, T. J., and Maines, M. D. (1997). Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur. J. Biochem. 247, 725-732. doi: 10.1111/j.1432-1033.1997.00725.x.
64. McDonnold, M., Tamayo, E., Kechichian, T., Gamble, P., Longo, M., Hankins, G. D., et al. (2014). The effect of prenatal pravastatin treatment on altered fetal programming of postnatal growth and metabolic function in a preeclampsia-like murine model. Am. J. Obstet. Gynecol. 210, 542.e1-542.e7. doi: 10.1016/j.ajog.2014.01.010.
65. McGettrick, A. F., and O'Neill, L. A. (2013). How metabolism generates signals during innate immunity and inflammation. J. Biol. Chem. 288, 22893-22898. doi: 10.1074/jbc.R113.486464.
66. Mold, J. E., Michaelsson, J., Burt, T. D., Muench, M. O., Beckerman, K. P., Busch, M. P., et al. (2008). Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science 322, 1562-1565. doi: 10.1126/science.1164511.
67. Molnarfi, N., Benkhoucha, M., Funakoshi, H., Nakamura, T., and Lalive, P. H. (2014). Hepatocyte growth factor: a regulator of inflammation and autoimmunity. Autoimmun. Rev. 14, 293-303. doi: 10.1016/j.autrev.2014.11.013.
68. Molnarfi, N., Benkhoucha, M., Juillard, C., Bjarnadottir, K., and Lalive, P. H. (2013). The neurotrophic hepatocyte growth factor induces protolerogenic human dendritic cells. J. Neuroimmunol. 267, 105-110. doi: 10.1016/j.jneuroim.2013.12.004.
69. Moreau, A., Hill, M., Thebault, P., Deschamps, J. Y., Chiffoleau, E., Chauveau, C., et al. (2009). Tolerogenic dendritic cells actively inhibit T cells through heme oxygenase-1 in rodents and in nonhuman primates. FASEB J. 23, 3070-3077. doi: 10.1096/fj.08-128173.
70. Muchova, L., Wong, R. J., Hsu, M., Morioka, I., Vitek, L., Zelenka, J., et al. (2007). Statin treatment increases formation of carbon monoxide and bilirubin in mice: a novel mechanism of in vivo antioxidant protection. Can. J. Physiol. Pharmacol. 85, 800-810. doi: 10.1139/y07-077.
71. Murphy, D. J. (2007). Epidemiology and environmental factors in preterm labour. Best Pract. Res. Clin. Obstet. Gynaecol. 21, 773-789. doi: 10.1016/j.bpobgyn.2007.03.001.
72. Nagamatsu, T., and Schust, D. J. (2010a). The contribution of macrophages to normal and pathological pregnancies. Am. J. Reprod. Immunol. 63, 460-471. doi: 10.1111/j.1600-0897.2010.00813.x.
73. Nagamatsu, T., and Schust, D. J. (2010b). The immunomodulatory roles of macrophages at the maternal-fetal interface. Reprod. Sci. 17, 209-218. doi: 10.1177/1933719109349962.
74. Nakagami, T., Toyomura, K., Kinoshita, T., and Morisawa, S. (1993). A beneficial role of bile pigments as an endogenous tissue protector: anti-complement effects of biliverdin and conjugated bilirubin. Biochim. Biophys. Acta 1158, 189-193. doi: 10.1016/0304-4165(93)90013-X.
75. Ndisang, J. F., and Mishra, M. (2013). The heme oxygenase system selectively suppresses the proinflammatory macrophage m1 phenotype and potentiates insulin signaling in spontaneously hypertensive rats. Am. J. Hypertens. 26, 1123-1131. doi: 10.1093/ajh/hpt082.
76. Patel, C. J., Yang, T., Hu, Z., Wen, Q., Sung, J., El-Sayed, Y. Y., et al. (2014). Investigation of maternal environmental exposures in association with self-reported preterm birth. Reprod. Toxicol. 45, 1-7. doi: 10.1016/j.reprotox.2013.12.005.
77. Patel, S. R., Copland, I. B., Garcia, M. A., Metz, R., and Galipeau, J. (2015). Human mesenchymal stromal cells suppress T-cell proliferation independent of heme oxygenase-1. Cytotherapy 17, 382-391. doi: 10.1016/j.jcyt.2014.11.010.
78. Pedroni, S. M., Gonzalez, J. M., Wade, J., Jansen, M. A., Serio, A., Marshall, I., et al. (2014). Complement inhibition and statins prevent fetal brain cortical abnormalities in a mouse model of preterm birth. Biochim. Biophys. Acta 1842, 107-115. doi: 10.1016/j.bbadis.2013.10.011.
79. Ramma, W., and Ahmed, A. (2011). Is inflammation the cause of pre-eclampsia? Biochem. Soc. Trans. 39, 1619-1627. doi: 10.1042/BST20110672.
80. Ramma, W., and Ahmed, A. (2014). Therapeutic potential of statins and the induction of heme oxygenase-1 in preeclampsia. J. Reprod. Immunol. 101-102, 153-160. doi: 10.1016/j.jri.2013.12.120.
81. Redecha, P., van Rooijen, N., Torry, D., and Girardi, G. (2009). Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury. Blood 113, 4101-4109. doi: 10.1182/blood-2008-12-194258.
82. Remy, S., Blancou, P., Tesson, L., Tardif, V., Brion, R., Royer, P. J., et al. (2009). Carbon monoxide inhibits TLR-induced dendritic cell immunogenicity. J. Immunol. 182, 1877-1884. doi: 10.4049/jimmunol.0802436.
83. Rieber, N., Gille, C., Kostlin, N., Schafer, I., Spring, B., Ost, M., et al. (2013). Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses. Clin. Exp. Immunol. 174, 45-52. doi: 10.1111/cei.12143.
84. Saito, S., Nakashima, A., Shima, T., and Ito, M. (2010). Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am. J. Reprod. Immunol. 63, 601-610. doi: 10.1111/j.1600-0897.2010.00852.x.
85. Schachtele, S. J., Hu, S., and Lokensgard, J. R. (2012). Modulation of experimental herpes encephalitis-associated neurotoxicity through sulforaphane treatment. PLoS ONE 7:e36216. doi: 10.1371/journal.pone.0036216.
86. Schisterman, E. F., Silver, R. M., Lesher, L. L., Faraggi, D., Wactawski-Wende, J., Townsend, J. M., et al. (2014). Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial. Lancet 384, 29-36. doi: 10.1016/S0140-6736(14)60157-4.
87. Schlossberger, V., Schober, L., Rehnitz, J., Schaier, M., Zeier, M., Meuer, S., et al. (2013). The success of assisted reproduction technologies in relation to composition of the total regulatory T cell (Treg) pool and different Treg subsets. Hum. Reprod. 28, 3062-3073. doi: 10.1093/humrep/det316.
88. Schober, L., Radnai, D., Schmitt, E., Mahnke, K., Sohn, C., and Steinborn, A. (2012). Term and preterm labor: decreased suppressive activity and changes in composition of the regulatory T-cell pool. Immunol. Cell Biol. 90, 935-944. doi: 10.1038/icb.2012.33.
89. Schroeder, B. M., and American College of Obstetricians and Gynecologists (ACOG). (2002). ACOG practice bulletin on diagnosing and managing preeclampsia and eclampsia. American College of Obstetricians and Gynecologists. Am. Fam. Physician 66, 330-331.
90. Schumacher, A., Wafula, P. O., Teles, A., El-Mousleh, T., Linzke, N., Zenclussen, M. L., et al. (2012). Blockage of heme oxygenase-1 abrogates the protective effect of regulatory T cells on murine pregnancy and promotes the maturation of dendritic cells. PLoS ONE 7:e42301. doi: 10.1371/journal.pone.0042301.
91. Shachar, B. Z., Carmichael, S. L., Stevenson, D. K., and Shaw, G. M. (2013). Could genetic polymorphisms related to oxidative stress modulate effects of heavy metals for risk of human preterm birth? Reprod. Toxicol. 42, 24-26. doi: 10.1016/j.reprotox.2013.06.072.
92. Shechter, R., London, A., and Schwartz, M. (2013). Orchestrated leukocyte recruitment to immune-privileged sites: absolute barriers versus educational gates. Nat. Rev. Immunol. 13, 206-218. doi: 10.1038/nri3391.
93. Showell, M. G., Brown, J., Clarke, J., and Hart, R. J. (2013). Antioxidants for female subfertility. Cochrane Database Syst. Rev. 8, CD007807. doi: 10.1002/14651858.CD007807.pub2.
94. Shynlova, O., Nedd-Roderique, T., Li, Y., Dorogin, A., and Lye, S. J. (2013a). Myometrial immune cells contribute to term parturition, preterm labour and post-partum involution in mice. J. Cell. Mol. Med. 17, 90-102. doi: 10.1111/j.1582-4934.2012.01650.x.
95. Shynlova, O., Nedd-Roderique, T., Li, Y., Dorogin, A., Nguyen, T., and Lye, S. J. (2013b). Infiltration of myeloid cells into decidua is a critical early event in the labour cascade and post-partum uterine remodelling. J. Cell. Mol. Med. 17, 311-324. doi: 10.1111/jcmm.12012.
96. Sica, A., and Mantovani, A. (2012). Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest. 122, 787-795. doi: 10.1172/JCI59643.
97. Skinner, M. K. (2014). Endocrine disruptor induction of epigenetic transgenerational inheritance of disease. Mol. Cell. Endocrinol. 398, 4-12. doi: 10.1016/j.mce.2014.07.019.
98. Soares, M. P., Marguti, I., Cunha, A., and Larsen, R. (2009). Immunoregulatory effects of HO-1: how does it work? Curr. Opin. Pharmacol. 9, 482-489. doi: 10.1016/j.coph.2009.05.008.
99. Sollwedel, A., Bertoja, A. Z., Zenclussen, M. L., Gerlof, K., Lisewski, U., Wafula, P., et al. (2005). Protection from abortion by heme oxygenase-1 up-regulation is associated with increased levels of Bag-1 and neuropilin-1 at the fetal-maternal interface. J. Immunol. 175, 4875-4885. doi: 10.4049/jimmunol.175.8.4875.
100. Stagg, J., and Galipeau, J. (2013). Mechanisms of immune modulation by mesenchymal stromal cells and clinical translation. Curr. Mol. Med. 13, 856-867. doi: 10.2174/1566524011313050016.
101. Steinborn, A., Schmitt, E., Stein, Y., Klee, A., Gonser, M., Seifried, E., et al. (2005). Prolonged preterm rupture of fetal membranes, a consequence of an increased maternal anti-fetal T cell responsiveness. Pediatr. Res. 58, 648-653. doi: 10.1203/01.PDR.0000180541.03425.76.
102. Tachibana, M., Hashino, M., Nishida, T., Shimizu, T., and Watarai, M. (2011). Protective role of heme oxygenase-1 in Listeria monocytogenes-induced abortion. PLoS ONE 6:e25046. doi: 10.1371/journal.pone.0025046.
103. Tachibana, M., Watanabe, K., Yamasaki, Y., Suzuki, H., and Watarai, M. (2008). Expression of heme oxygenase-1 is associated with abortion caused by Brucella abortus infection in pregnant mice. Microb. Pathog. 45, 105-109. doi: 10.1016/j.micpath.2008.04.002.
104. Takeda, N., O'Dea, E. L., Doedens, A., Kim, J. W., Weidemann, A., Stockmann, C., et al. (2010). Differential activation and antagonistic function of HIF-a isoforms in macrophages are essential for NO homeostasis. Genes Dev. 24, 491-501. doi: 10.1101/gad.1881410.
105. Teles, A., Thuere, C., Wafula, P. O., El-Mousleh, T., Zenclussen, M. L., and Zenclussen, A. C. (2013). Origin of Foxp3+ cells during pregnancy. Am. J. Clin. Exp. Immunol. 2, 222-233.
106. Tenhola, S., Rahiala, E., Martikainen, A., Halonen, P., and Voutilainen, R. (2003). Blood pressure, serum lipids, fasting insulin, and adrenal hormones in 12-year-old children born with maternal preeclampsia. J. Clin. Endocrinol. Metab. 88, 1217-1222. doi: 10.1210/jc.2002-020903.
107. Thomson, A. J., Telfer, J. F., Young, A., Campbell, S., Stewart, C. J., Cameron, I. T., et al. (1999). Leukocytes infiltrate the myometrium during human parturition: further evidence that labour is an inflammatory process. Hum. Reprod. 14, 229-236. doi: 10.1093/humrep/14.1.229.
108. Tullius, S. G., Nieminen-Kelha, M., Buelow, R., Reutzel-Selke, A., Martins, P. N., Pratschke, J., et al. (2002). Inhibition of ischemia/reperfusion injury and chronic graft deterioration by a single-donor treatment with cobalt-protoporphyrin for the induction of heme oxygenase-1. Transplantation 74, 591-598. doi: 10.1097/00007890-200209150-00001.
109. Vatten, L. J., Romundstad, P. R., Holmen, T. L., Hsieh, C. C., Trichopoulos, D., and Stuver, S. O. (2003). Intrauterine exposure to preeclampsia and adolescent blood pressure, body size, and age at menarche in female offspring. Obstet. Gynecol. 101, 529-533. doi: 10.1016/S0029-7844(02)02718-7.
110. Vince, G. S., Starkey, P. M., Jackson, M. C., Sargent, I. L., and Redman, C. W. (1990). Flow cytometric characterisation of cell populations in human pregnancy decidua and isolation of decidual macrophages. J. Immunol. Methods 132, 181-189. doi: 10.1016/0022-1759(90)90028-T.
111. Wallace, A. E., Whitley, G. S., Thilaganathan, B., and Cartwright, J. E. (2015). Decidual natural killer cell receptor expression is altered in pregnancies with impaired vascular remodeling and a higher risk of pre-eclampsia. J. Leukoc. Biol. 97, 79-86. doi: 10.1189/jlb.2A0614-282R.
112. Wegiel, B., Hanto, D. W., and Otterbein, L. E. (2013). The social network of carbon monoxide in medicine. Trends Mol. Med. 19, 3-11. doi: 10.1016/j.molmed.2012.10.001.
113. Weinberger, B., Archer, F. E., Kathiravan, S., Hirsch, D. S., Kleinfeld, A. M., Vetrano, A. M., et al. (2013). Effects of bilirubin on neutrophil responses in newborn infants. Neonatology 103, 105-111. doi: 10.1159/000343097.
114. Wong, R. J., Zhao, H., and Stevenson, D. K. (2012). A deficiency in haem oxygenase-1 induces foetal growth restriction by placental vasculature defects. Acta Paediatr. 101, 827-834. doi: 10.1111/j.1651-2227.2012.02729.x.
115. Woo, J., Iyer, S., Cornejo, M. C., Mori, N., Gao, L., Sipos, I., et al. (1998). Stress protein-induced immunosuppression: inhibition of cellular immune effector functions following overexpression of haem oxygenase (HSP 32). Transpl. Immunol. 6, 84-93. doi: 10.1016/S0966-3274(98)80022-1.
116. Woudwyk, M. A., Monteavaro, C. E., Jensen, F., Soto, P., Barbeito, C. G., and Zenclussen, A. C. (2012). Study of the uterine local immune response in a murine model of embryonic death due to Tritrichomonas foetus. Am. J. Reprod. Immunol. 68, 128-137. doi: 10.1111/j.1600-0897.2012.01159.x.
117. Wu, L., Luo, L. H., Zhang, Y. X., Li, Q., Xu, B., Zhou, G. X., et al. (2014). Alteration of Th17 and Treg cells in patients with unexplained recurrent spontaneous abortion before and after lymphocyte immunization therapy. Reprod. Biol. Endocrinol. 12, 74. doi: 10.1186/1477-7827-12-74.
118. Yuen, T. J., Silbereis, J. C., Griveau, A., Chang, S. M., Daneman, R., Fancy, S. P., et al. (2014). Oligodendrocyte-encoded HIF function couples postnatal myelination and white matter angiogenesis. Cell 158, 383-396. doi: 10.1016/j.cell.2014.04.052.
119. Zelenay, S., Chora, A., Soares, M. P., and Demengeot, J. (2007). Heme oxygenase-1 is not required for mouse regulatory T cell development and function. Int. Immunol. 19, 11-18. doi: 10.1093/intimm/dxl116.
120. Zenclussen, A. C., Schumacher, A., Zenclussen, M. L., Wafula, P., and Volk, H. D. (2007). Immunology of pregnancy: cellular mechanisms allowing fetal survival within the maternal uterus. Expert Rev. Mol. Med. 9, 1-14. doi: 10.1017/S1462399407000294.
121. Zenclussen, A. C., Sollwedel, A., Bertoja, A. Z., Gerlof, K., Zenclussen, M. L., Woiciechowsky, C., et al. (2005). Heme oxygenase as a therapeutic target in immunological pregnancy complications. Int. Immunopharmacol. 5, 41-51. doi: 10.1016/j.intimp.2004.09.011.
122. Zenclussen, M. L., Anegon, I., Bertoja, A. Z., Chauveau, C., Vogt, K., Gerlof, K., et al. (2006). Over-expression of heme oxygenase-1 by adenoviral gene transfer improves pregnancy outcome in a murine model of abortion. J. Reprod. Immunol. 69, 35-52. doi: 10.1016/j.jri.2005.10.001.
123. Zenclussen, M. L., Casalis, P. A., El-Mousleh, T., Rebelo, S., Langwisch, S., Linzke, N., et al. (2011). Haem oxygenase-1 dictates intrauterine fetal survival in mice via carbon monoxide. J. Pathol. 225, 293-304. doi: 10.1002/path.2946.
124. Zenclussen, M. L., Casalis, P. A., Jensen, F., Woidacki, K., and Zenclussen, A. C. (2014). Hormonal fluctuations during the estrous cycle modulate heme oxygenase-1 expression in the uterus. Front. Endocrinol. (Lausanne) 5:32. doi: 10.3389/fendo.2014.00032.
125. Zenclussen, M. L., Jensen, F., Rebelo, S., El-Mousleh, T., Casalis, P. A., and Zenclussen, A. C. (2012). Heme oxygenase-1 expression in the ovary dictates a proper oocyte ovulation, fertilization, and corpora lutea maintenance. Am. J. Reprod. Immunol. 67, 376-382. doi: 10.1111/j.1600-0897.2011.01096.x.
126. Zhao, H., Azuma, J., Kalish, F., Wong, R. J., and Stevenson, D. K. (2011). Maternal heme oxygenase 1 regulates placental vasculature development via angiogenic factors in mice. Biol. Reprod. 85, 1005-1012. doi: 10.1095/biolreprod.111.093039.
127. Zhao, H., Kalish, F., Schulz, S., Yang, Y., Wong, R. J., and Stevenson, D. K. (2015). Unique roles of infiltrating myeloid cells in the murine uterus during early and mid-pregnancy. J. Immunol. 194, 3713-3722. doi: 10.4049/jimmunol.1401930.
128. Zhao, H., Wong, R. J., Doyle, T. C., Nayak, N., Vreman, H. J., Contag, C. H., et al. (2008). Regulation of maternal and fetal hemodynamics by heme oxygenase in mice. Biol. Reprod. 78, 744-751. doi: 10.1095/biolreprod.107.064899.
129. Zhao, H., Wong, R. J., Kalish, F. S., Nayak, N. R., and Stevenson, D. K. (2009). Effect of heme oxygenase-1 deficiency on placental development. Placenta 30, 861-868. doi: 10.1016/j.placenta.2009.07.012.
130. + regulatory T cell pool during pregnancy. J. Reprod. Immunol. 75, 71-81. doi: 10.1016/j.jri.2007.06.052.
131. Zoso, A., Mazza, E. M., Bicciato, S., Mandruzzato, S., Bronte, V., Serafini, P., et al. (2014). Human fibrocytic myeloid-derived suppressor cells express IDO and promote tolerance via Treg-cell expansion. Eur. J. Immunol. 44, 3307-3319. doi: 10.1002/eji.201444522.