Smoke exposure causes endoplasmic reticulum stress and lipid accumulation in retinal pigment epithelium through oxidative stress and complement activation

Journal of Biological Chemistry

Volumn 289, Issue 21, 2014, Pages 14534-14546

  Kunchithapautham, Kannan ^a   Atkinson, Carl ^a   Rohrer, Bärbel ^a,b  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^b RALPH H JOHNSON VA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL MEMBRANES; CELL SIGNALING; CHEMICAL ACTIVATION; SMOKE;

AGE-RELATED MACULAR DEGENERATION; COMPLEMENT ACTIVATIONS; ENDOPLASMIC RETICULUM STRESS; LIPID ACCUMULATIONS; LIPID DEPOSITION; RETINAL PIGMENT EPITHELIUM; RPE CELL; SMOKE COMPONENTS;

OXIDATIVE STRESS;

CIGARETTE SMOKE; COMPLEMENT; COMPLEMENT COMPONENT C3; COMPLEMENT COMPONENT C3A; LIPID;

ANIMAL EXPERIMENT; ARTICLE; CELL MEMBRANE; COMPLEMENT ACTIVATION; COMPLEMENT ALTERNATIVE PATHWAY; CONTROLLED STUDY; ENDOPLASMIC RETICULUM STRESS; ENZYME LINKED IMMUNOSORBENT ASSAY; EXPOSURE; HUMAN; HUMAN CELL; IMMUNOCYTOCHEMISTRY; KNOCKOUT MOUSE; LIPID HOMEOSTASIS; LIPID STORAGE; MALE; MOUSE; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PIGMENT EPITHELIUM; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; WESTERN BLOTTING;

AGE-RELATED MACULAR DEGENERATION; COMPLEMENT SYSTEM; ER STRESS; LIPODYSTROPHY; MITOCHONDRIA; OXIDATIVE STRESS; SMOKING; UNFOLDED PROTEIN RESPONSE;

ACETYLCYSTEINE; ANIMALS; ARGININE; BENZHYDRYL COMPOUNDS; BLOTTING, WESTERN; CELLS, CULTURED; COMPLEMENT ACTIVATION; COMPLEMENT FACTOR B; COMPLEMENT PATHWAY, ALTERNATIVE; ENDOPLASMIC RETICULUM STRESS; FREE RADICAL SCAVENGERS; HEAT-SHOCK PROTEINS; HUMANS; LIPIDS; MACULAR DEGENERATION; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; NICOTINE; OXIDATIVE STRESS; RECEPTORS, COMPLEMENT; RETINAL PIGMENT EPITHELIUM; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SMOKE; TOBACCO; TRANSCRIPTION FACTOR CHOP;

EID: 84901398187     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.564674     Document Type: Article

References (78)

1. Ferris, F. L., 3rd, Wilkinson, C. P., Bird, A., Chakravarthy, U., Chew, E., Csaky, K., Sadda, S. R., and Beckman Initiative for Macular Research Classification, C. (2013) Clinical classification of age-related macular degeneration. Ophthalmology 120, 844-851
2. Brown, M. M., Brown, G. C., Stein, J. D., Roth, Z., Campanella, J., and Beauchamp, G. R. (2005) Age-related macular degeneration: economic burden and value-based medicine analysis. Can. J. Ophthalmol. 40, 277-287 (Pubitemid 40942254)
3. Freund, K. B., Zweifel, S. A., and Engelbert, M. (2010) Do we need a new classification for choroidal neovascularization in age-related macular degeneration? Retina 30, 1333-1349
4. Hageman, G. S., Luthert, P. J., Victor Chong, N. H., Johnson, L. V., Anderson, D. H., and Mullins, R. F. (2001) An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPEBruch's membrane interface in aging and age-related macular degeneration. Prog. Retin. Eye Res. 20, 705-732 (Pubitemid 32918285)
5. Edwards, A. O., Ritter, R., 3rd, Abel, K. J., Manning, A., Panhuysen, C., and Farrer, L. A. (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308, 421-424 (Pubitemid 40530082)
6. Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., Smith, R. J., Silvestri, G., Russell, S. R., Klaver, C. C., Barbazetto, I., Chang, S., Yannuzzi, L. A., Barile, G. R., Merriam, J. C., Smith, R. T., Olsh, A. K., Bergeron, J., Zernant, J., Merriam, J. E., Gold, B., Dean, M., and Allikmets, R. (2005) A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc. Natl. Acad. Sci. U.S.A. 102, 7227-7232 (Pubitemid 40696361)
7. Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., Schnetz- Boutaud, N., Agarwal, A., Postel, E. A., and Pericak-Vance, M. A. (2005) Complement factor H variant increases the risk of age-related macular degeneration. Science 308, 419-421 (Pubitemid 40530081)
8. Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J. Y., Sackler, R. S., Haynes, C., Henning, A. K., SanGiovanni, J. P., Mane, S. M., Mayne, S. T., Bracken, M. B., Ferris, F. L., Ott, J., Barnstable, C., and Hoh, J. (2005) Complement factorHpolymorphism in age-related macular degeneration. Science 308, 385-389 (Pubitemid 40530070)
9. Zarbin, M. A., and Rosenfeld, P. J. (2010) Pathway-based therapies for age-related macular degeneration: an integrated survey of emerging treatment alternatives. Retina 30, 1350-1367
10. Whitcup, S. M., Sodhi, A., Atkinson, J. P., Holers, V. M., Sinha, D., Rohrer, B., and Dick, A. D. (2013) The role of the immune response in age-related macular degeneration. Int. J. Inflam. 2013, 348092
11. Müller-Eberhard, H. J. (1988) Molecular organization and function of the complement system. Annu. Rev. Biochem. 57, 321-347
12. Thurman, J. M., Ljubanovi, D., Royer, P. A., Kraus, D. M., Molina, H., Barry, N. P., Proctor, G., Levi, M., and Holers, V. M. (2006) Altered renal tubular expression of the complement inhibitor Crry permits complement activation after ischemia/reperfusion. J. Clin. Invest. 116, 357-368 (Pubitemid 43228352)
13. Yang, P., Tyrrell, J., Han, I., and Jaffe, G. J. (2009) Expression and modulation of RPE cell membrane complement regulatory proteins. Invest. Ophthalmol. Vis. Sci. 50, 3473-3481
14. Yin, W., Ghebrehiwet, B., Weksler, B., and Peerschke, E. I. (2008) Regulated complement deposition on the surface of human endothelial cells: effect of tobacco smoke and shear stress. Thromb. Res. 122, 221-228
15. Fett, A. L., Hermann, M. M., Muether, P. S., Kirchhof, B., and Fauser, S. (2012) Immunohistochemical localization of complement regulatory proteins in the human retina. Histol. Histopathol. 27, 357-364
16. Vogt, S. D., Curcio, C. A., Wang, L., Li, C. M., McGwin, G., Jr., Medeiros, N. E., Philp, N. J., Kimble, J. A., and Read, R. W. (2011) Retinal pigment epithelial expression of complement regulator CD46 is altered early in the course of geographic atrophy. Exp. Eye Res. 93, 413-423
17. Ebrahimi, K. B., Fijalkowski, N., Cano, M., and Handa, J. T. (2013) Decreased membrane complement regulators in the retinal pigmented epithelium contributes to age-related macular degeneration. J. Pathol. 229, 729-742
18. Anderson, D. H., Radeke, M. J., Gallo, N. B., Chapin, E. A., Johnson, P. T., Curletti, C. R., Hancox, L. S., Hu, J., Ebright, J. N., Malek, G., Hauser, M. A., Rickman, C. B., Bok, D., Hageman, G. S., and Johnson, L. V. (2010) The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Prog. Retin. Eye Res. 29, 95-112
19. Lois, N., Abdelkader, E., Reglitz, K., Garden, C., and Ayres, J. G. (2008) Environmental tobacco smoke exposure and eye disease. Br. J. Ophthalmol. 92, 1304-1310
20. Chakravarthy, U., Augood, C., Bentham, G. C., de Jong, P. T., Rahu, M., Seland, J., Soubrane, G., Tomazzoli, L., Topouzis, F., Vingerling, J. R., Vioque, J., Young, I. S., and Fletcher, A. E. (2007) Cigarette smoking and age-related macular degeneration in the EUREYE study. Ophthalmology 114, 1157-1163 (Pubitemid 46829372)
21. Mitchell, P., Wang, J. J., Smith, W., and Leeder, S. R. (2002) Smoking and the 5-year incidence of age-related maculopathy: the Blue Mountains Eye Study. Arch. Ophthalmol. 120, 1357-1363 (Pubitemid 36105441)
22. Khan, J. C., Thurlby, D. A., Shahid, H., Clayton, D. G., Yates, J. R., Bradley, M., Moore, A. T., Bird, A. C., and Genetic Factors in AMD Study. (2006) Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularisation. Br. J. Ophthalmol. 90, 75-80 (Pubitemid 43029901)
23. Church, D. F., and Pryor, W. A. (1985) Free-radical chemistry of cigarette smoke and its toxicological implications. Environ. Health Perspect. 64, 111-126 (Pubitemid 16135783)
24. van der Vaart, H., Postma, D. S., Timens, W., and ten Hacken, N. H. (2004) Acute effects of cigarette smoke on inflammation and oxidative stress: A review. Thorax 59, 713-721 (Pubitemid 39061538)
25. Kew, R. R., Ghebrehiwet, B., and Janoff, A. (1985) Cigarette smoke can activate the alternative pathway of complement in vitro by modifying the third component of complement. J. Clin. Invest. 75, 1000-1007 (Pubitemid 15115269)
26. Sanai, M., and Hussain, N. (2011) Levels of inflammatory markers (complement C3, complement C4 and C-reactive protein) in smokers. Afr. J. Biotechnol. 10, 19211-19217
27. Wang, A. L., Lukas, T. J., Yuan, M., Du, N., Handa, J. T., and Neufeld, A. H. (2009) Changes in retinal pigment epithelium related to cigarette smoke: possible relevance to smoking as a risk factor for age-related macular degeneration. PLoS ONE 4, e5304
28. Woodell, A., Coughlin, B., Kunchithapautham, K., Casey, S., Williamson, T., Ferrell, W. D., Atkinson, C., Jones, B. W., and Rohrer, B. (2013) Alternative complement pathway deficiency ameliorates chronic smoke-induced functional and morphological ocular injury. PLoS ONE 8, e67894
29. Kelsen, S. G. (2012) Respiratory epithelial cell responses to cigarette smoke: the unfolded protein response. Pulm. Pharmacol. Ther 25, 447-452
30. Tweed, J. O., Hsia, S. H., Lutfy, K., and Friedman, T. C. (2012) The endocrine effects of nicotine and cigarette smoke. Trends Endocrinol. Metab. 23, 334-342
31. Walter, P., and Ron, D. (2011) The unfolded protein response: from stress pathway to homeostatic regulation. Science 334, 1081-1086
32. Ishida, Y., Yamamoto, A., Kitamura, A., Lamandé, S. R., Yoshimori, T., Bateman, J. F., Kubota, H., and Nagata, K. (2009) Autophagic elimination of misfolded procollagen aggregates in the endoplasmic reticulum as a means of cell protection. Mol. Biol. Cell 20, 2744-2754
33. Kitamura, M. (2008) Endoplasmic reticulum stress and unfolded protein response in renal pathophysiology: Janus faces. Am. J. Physiol. Renal Physiol. 295, F323-334
34. Meusser, B., Hirsch, C., Jarosch, E., and Sommer, T. (2005) ERAD: the long road to destruction. Nat. Cell Biol. 7, 766-772 (Pubitemid 41079045)
35. Haeri, M., and Knox, B. E. (2012) Endoplasmic reticulum stress and unfolded protein response pathways: potential for treating age-related retinal degeneration. J. Ophthalmic. Vis. Res. 7, 45-59
36. Ni, M., Zhang, Y., and Lee, A. S. (2011) Beyond the endoplasmic reticulum: atypical GRP78 in cell viability, signalling and therapeutic targeting. Biochem. J. 434, 181-188
37. Haimovici, R., Gantz, D. L., Rumelt, S., Freddo, T. F., and Small, D. M. (2001) The lipid composition of drusen, Bruch's membrane, and sclera by hot stage polarizing light microscopy. Invest. Ophthalmol. Vis. Sci. 42, 1592-1599 (Pubitemid 32520753)
38. Wang, L., Clark, M. E., Crossman, D. K., Kojima, K., Messinger, J. D., Mobley, J. A., and Curcio, C. A. (2010) Abundant lipid and protein components of drusen. PLoS ONE 5, e10329
39. Curcio, C. A., Millican, C. L., Bailey, T., and Kruth, H. S. (2001) Accumulation of cholesterol with age in human Bruch's membrane. Invest. Ophthalmol. Vis. Sci. 42, 265-274 (Pubitemid 32059440)
40. Ebrahimi, K. B., and Handa, J. T. (2011) Lipids, lipoproteins, and agerelated macular degeneration. J. Lipids 2011, 802059
41. Colgan, S. M., Hashimi, A. A., and Austin, R. C. (2011) Endoplasmic reticulum stress and lipid dysregulation. Expert Rev. Mol. Med. 13, e4
42. Damiano, F., Alemanno, S., Gnoni, G. V., and Siculella, L. (2010) Translational control of the sterol-regulatory transcription factor SREBP-1 mRNA in response to serum starvation or ER stress is mediated by an internal ribosome entry site. Biochem. J. 429, 603-612
43. Matsumoto, M., Fukuda, W., Circolo, A., Goellner, J., Strauss-Schoenberger, J., Wang, X., Fujita, S., Hidvegi, T., Chaplin, D. D., and Colten, H. R. (1997) Abrogation of the alternative complement pathway by targeted deletion of murine factor B. Proc. Natl. Acad. Sci. U.S.A. 94, 8720-8725 (Pubitemid 27335106)
44. Huang, Y., Qiao, F., Atkinson, C., Holers, V. M., and Tomlinson, S. (2008) A novel targeted inhibitor of the alternative pathway of complement and its therapeutic application in ischemia/reperfusion injury. J. Immunol. 181, 8068-8076
45. Thurman, J. M., Kulik, L., Orth, H., Wong, M., Renner, B., Sargsyan, S. A., Mitchell, L. M., Hourcade, D. E., Hannan, J. P., Kovacs, J. M., Coughlin, B., Woodell, A. S., Pickering, M. C., Rohrer, B., and Holers, V. M. (2013) Detection of complement activation using monoclonal antibodies against C3d. J. Clin. Invest. 123, 2218-2230
46. Thurman, J. M., Renner, B., Kunchithapautham, K., Ferreira, V. P., Pangburn, M. K., Ablonczy, Z., Tomlinson, S., Holers, V. M., and Rohrer, B. (2009) Oxidative stress renders retinal pigment epithelial cells susceptible to complement-mediated injury. J. Biol. Chem. 284, 16939-16947
47. Ablonczy, Z., and Crosson, C. E. (2007) VEGF modulation of retinal pigment epithelium resistance. Exp. Eye Res. 85, 762-771 (Pubitemid 350166363)
48. Mulligan, R. M., Atkinson, C., Vertegel, A. A., Reukov, V., and Schlosser, R. J. (2009) Cigarette smoke extract stimulates interleukin-8 production in human airway epithelium and is attenuated by superoxide dismutase in vitro. Am. J. Rhinol. Allergy 23, e1-4
49. Rudolf, M., and Curcio, C. A. (2009) Esterified cholesterol is highly localized to Bruch's membrane, as revealed by lipid histochemistry in wholemounts of human choroid. J. Histochem. Cytochem. 57, 731-739
50. Lohr, H. R., Kuntchithapautham, K., Sharma, A. K., and Rohrer, B. (2006) Multiple, parallel cellular suicide mechanisms participate in photoreceptor cell death. Exp. Eye Res. 83, 380-389 (Pubitemid 43850954)
51. Samali, A., Fitzgerald, U., Deegan, S., and Gupta, S. (2010) Methods for monitoring endoplasmic reticulum stress and the unfolded protein response. Int. J. Cell Biol. 2010, 830307
52. Dithmar, S., Curcio, C. A., Le, N. A., Brown, S., and Grossniklaus, H. E. (2000) Ultrastructural changes in Bruch's membrane of apolipoprotein E-deficient mice. Invest. Ophthalmol. Vis. Sci. 41, 2035-2042 (Pubitemid 30450970)
53. Davis, K. S., Casey, S. E., Mulligan, J. K., Mulligan, R. M., Schlosser, R. J., and Atkinson, C. (2010) Murine complement deficiency ameliorates acute cigarette smoke-induced nasal damage. Otolaryngol. Head Neck Surg. 143, 152-158
54. Rózanowska, M., Jarvis-Evans, J., Korytowski, W., Boulton, M. E., Burke, J. M., and Sarna, T. (1995) Blue light-induced reactivity of retinal age pigment: in vitro generation of oxygen-reactive species. J. Biol. Chem. 270, 18825-18830
55. Liles, M. R., Newsome, D. A., and Oliver, P. D. (1991) Antioxidant enzymes in the aging human retinal pigment epithelium. Arch. Ophthalmol. 109, 1285-1288
56. Tate, D. J., Jr., Oliver, P. D., Miceli, M. V., Stern, R., Shuster, S., and Newsome, D. A. (1993) Age-dependent change in the hyaluronic acid content of the human chorioretinal complex. Arch. Ophthalmol. 111, 963-967 (Pubitemid 23208804)
57. Joseph, K., Kulik, L., Coughlin, B., Kunchithapautham, K., Bandyopadhyay, M., Thiel, S., Thielens, N. M., Holers, V. M., and Rohrer, B. (2013) Oxidative stress sensitizes RPE cells to complement-mediated injury in a natural antibody-, lectin pathway-, and phospholipid epitope-dependent manner. J. Biol. Chem. 288, 12753-12765
58. Bandyopadhyay, M., and Rohrer, B. (2012) Matrix metalloproteinase activity creates pro-angiogenic environment in primary human retinal pigment epithelial cells exposed to complement. Invest. Ophthalmol. Vis. Sci. 53, 1953-1961
59. Zipfel, P. F., Lauer, N., and Skerka, C. (2010) The role of complement in AMD. Adv. Exp. Med. Biol. 703, 9-24
60. Espinosa-Heidmann, D. G., Suner, I. J., Catanuto, P., Hernandez, E. P., Marin-Castano, M. E., and Cousins, S. W. (2006) Cigarette smoke-related oxidants and the development of sub-RPE deposits in an experimental animal model of dry AMD. Invest. Ophthalmol. Vis. Sci. 47, 729-737 (Pubitemid 46768404)
61. Yu, A. L., Birke, K., Burger, J., and Welge-Lussen, U. (2012) Biological effects of cigarette smoke in cultured human retinal pigment epithelial cells. PLoS ONE 7, e48501
62. Bertram, K. M., Baglole, C. J., Phipps, R. P., and Libby, R. T. (2009) Molecular regulation of cigarette smoke induced-oxidative stress in human retinal pigment epithelial cells: implications for age-related macular degeneration. Am. J. Physiol. Cell Physiol. 297, C1200-1210
63. Coffey, P. J., Gias, C., McDermott, C. J., Lundh, P., Pickering, M. C., Sethi, C., Bird, A., Fitzke, F. W., Maass, A., Chen, L. L., Holder, G. E., Luthert, P. J., Salt, T. E., Moss, S. E., and Greenwood, J. (2007) Complement factor Hdeficiency in aged mice causes retinal abnormalities and visual dysfunction. Proc. Natl. Acad. Sci. U.S.A. 104, 16651-16656 (Pubitemid 350211071)
64. Yu, M., Zou, W., Peachey, N. S., McIntyre, T. M., and Liu, J. (2012)Anovel role of complement in retinal degeneration. Invest. Ophthalmol. Vis. Sci. 53, 7684-7692
65. Lundh von Leithner, P., Kam, J. H., Bainbridge, J., Catchpole, I., Gough, G., Coffey, P., and Jeffery, G. (2009) Complement factor H is critical in the maintenance of retinal perfusion. Am. J. Pathol. 175, 412-421
66. Kunchithapautham, K., Bandyopadhyay, M., Dahrouj, M., Thurman, J. M., and Rohrer, B. (2012) Sublytic membrane-attack complex activation and VEGF secretion in retinal pigment epithelial cells. Adv. Exp. Med. Biol. 723, 23-30
67. Lin, J. H., and Lavail, M. M. (2010) Misfolded proteins and retinal dystrophies. Adv. Exp. Med. Biol. 664, 115-121
68. Salminen, A., Kauppinen, A., Hyttinen, J. M., Toropainen, E., and Kaarniranta, K. (2010) Endoplasmic reticulum stress in age-related macular degeneration: trigger for neovascularization. Mol. Med. 16, 535-542
69. Roybal, C. N., Yang, S., Sun, C. W., Hurtado, D., Vander Jagt, D. L., Townes, T. M., and Abcouwer, S. F. (2004) Homocysteine increases the expression of vascular endothelial growth factor by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4. J. Biol. Chem. 279, 14844-14852 (Pubitemid 38618874)
70. Ishida, B. Y., Bailey, K. R., Duncan, K. G., Chalkley, R. J., Burlingame, A. L., Kane, J. P., and Schwartz, D.M.(2004) Regulated expression of apolipoprotein E by human retinal pigment epithelial cells. J. Lipid Res. 45, 263-271 (Pubitemid 38228823)
71. Wang, L., Li, C. M., Rudolf, M., Belyaeva, O. V., Chung, B. H., Messinger, J. D., Kedishvili, N. Y., and Curcio, C. A. (2009) Lipoprotein particles of intraocular origin in human Bruch membrane: an unusual lipid profile. Invest. Ophthalmol. Vis. Sci. 50, 870-877
72. Johnson, L. V., Forest, D. L., Banna, C. D., Radeke, C. M., Maloney, M. A., Hu, J., Spencer, C. N., Walker, A. M., Tsie, M. S., Bok, D., Radeke, M. J., and Anderson, D. H. (2011) Cell culture model that mimics drusen formation and triggers complement activation associated with age-related macular degeneration. Proc. Natl. Acad. Sci. U.S.A. 108, 18277-18282
73. Klos, A., Wende, E., Wareham, K. J., and Monk, P. N. (2013) International Union of Pharmacology. LXXXVII: complement peptide C5a, C4a, and C3a receptors. Pharmacol. Rev. 65, 500-543
74. Mogilenko, D. A., Kudriavtsev, I. V., Trulioff, A. S., Shavva, V. S., Dizhe, E. B., Missyul, B. V., Zhakhov, A. V., Ischenko, A. M., Perevozchikov, A. P., and Orlov, S. V. (2012) Modified low density lipoprotein stimulates complement C3 expression and secretion via liver X receptor and Toll-like receptor 4 activation in human macrophages. J. Biol. Chem. 287, 5954-5968
75. Damman, J., Nijboer, W. N., Schuurs, T. A., Leuvenink, H. G., Morariu, A. M., Tullius, S. G., van Goor, H., Ploeg, R. J., and Seelen, M. A. (2011) Local renal complement C3 induction by donor brain death is associated with reduced renal allograft function after transplantation. Nephrol. Dial. Transplant. 26, 2345-2354
76. Platel, D., Guiguet, M., Briere, F., Bernard, A., and Mack, G. (1994) Human interleukin-6 acts as a co-factor for the up-regulation of C3 production by rat liver epithelial cells. Eur. Cytokine Netw. 5, 405-410 (Pubitemid 24292677)
77. Luo, C., Chen, M., and Xu, H. (2011) Complement gene expression and regulation in mouse retina and retinal pigment epithelium/choroid. Mol. Vis. 17, 1588-1597
78. Yun, L., Nicholas, H., Mark, A., Madesh, M., and Steven, K. (2012) Cigarette smoke-induced reactive oxygen species (ROS) production in human airway epithelial cells is calcium and NADPH-oxidase (NOX) dependent. in C53.COPD pathogenesis: in vitro and in vivo studies, pp. A4561-A4561, American Thoracic Society, New York