Genome-wide transcriptional response of primary alveolar macrophages following infection with porcine reproductive and respiratory syndrome virus

Journal of General Virology

Volumn 89, Issue 10, 2008, Pages 2550-2564

  Genini, Sem ^a   Delputte, Peter L ^b   Malinverni, Roberto ^a   Cecere, Maria ^a   Stella, Alessandra ^a   Nauwynck, Hans J ^b   Giuffra, Elisabetta ^a  

^a PARCO TECNOLOGICO PADANO   (Italy)

^b GHENT UNIVERSITY   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; BETA INTERFERON; INTERLEUKIN 10; TUMOR NECROSIS FACTOR ALPHA; PROTEIN;

ANIMAL EXPERIMENT; ARTERIVIRUS; ARTICLE; DOWN REGULATION; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; HELPER CELL; IN VITRO STUDY; INNATE IMMUNITY; LUNG ALVEOLUS MACROPHAGE; MICROARRAY ANALYSIS; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; REAL TIME POLYMERASE CHAIN REACTION; SWINE; UPREGULATION; VIRUS GENOME; VIRUS INFECTION; VIRUS REPLICATION; VIRUS STRAIN; VIRUS TRANSCRIPTION; ANIMAL; DNA MICROARRAY; GENETIC TRANSCRIPTION; GENETICS; IMMUNOLOGY; METABOLISM; METHODOLOGY; PATHOGENICITY; POLYMERASE CHAIN REACTION; TIME; VIROLOGY;

PORCINE RESPIRATORY AND REPRODUCTIVE SYNDROME VIRUS; SUIDAE; SUS;

ANIMALS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENOME, VIRAL; MACROPHAGES, ALVEOLAR; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; POLYMERASE CHAIN REACTION; PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME; PORCINE RESPIRATORY AND REPRODUCTIVE SYNDROME VIRUS; PROTEINS; SWINE; TIME FACTORS; TRANSCRIPTION, GENETIC; VIRUS REPLICATION;

EID: 54449101701     PISSN: 00221317     EISSN: None     Source Type: Journal    
DOI: 10.1099/vir.0.2008/003244-0     Document Type: Article

References (85)

1. Ait-Ali, T., Wilson, A., Wescott, D. G., Clapperton, M., Mellencamp, M., Drew, T. W., Bishop, S. C. & Archibald, A. (2007). Innate immune responses to replication of porcine reproductive and respiratory syndrome virus in isolated swine alveolar macrophages. Viral Immunol 20, 105-118.
2. Albina, E., Carrat, C. & Charley, B. (1998). Interferon-α response to swine arterivirus (PoAV), the porcine reproductive and respiratory syndrome virus. J Interferon Cytokine Res 18, 485-490.
3. Allende, R., Laegreid, W. W., Kutish, G. F., Galeota, J. A., Wills, R. W. & Osorio, F. A. (2000). Porcine reproductive and respiratory syndrome virus: description of persistence in individual pigs upon experimental infection. J Virol 74, 10834-10837.
4. Beyer, J., Fichtner, D., Schirrmeier, H., Polster, U., Weiland, E. & Wege, H. (2000). Porcine reproductive and respiratory syndrome virus (PRRSV): kinetics of infection in lymphatic organs and lung. J Vet Med B Infect Dis Vet Public Health 47, 9-25.
5. Bi, G. R., Zhang, H., Zhou, H. J., Bai, L. J., Zhang, H. M., Hai, H. & Fang, X. B. (2007). Effect of adrenomedulin on neuron apoptosis and early growth response gene-1 after focal ischemia/ reperfusion in rats. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 19, 353-357.
6. Biron, A. B. & Sen, G. C. (2001). Interferons and other cytokines. In Fields Virology, 4th edn, pp. 321-351. Edited by B. N. Fields & D. M. Knipe. Philadelphia: Lippincott Williams & Wilkins.
7. Brazma, A., Hingamp, P., Quackenbush, J., Sherlock, G., Spellman, P., Stoeckert, C., Aach, J., Ansorge, W., Ball, C. A. & other authors (2001). Minimum information about a microarray experiment (MIAME) - toward standards for microarray data. Nat Genet 29, 365-371.
8. Bruder, J. T. & Kovesdi, I. (1997). Adenovirus infection stimulates the Raf/MAPK signaling pathway and induces interleukin-8 expression. J Virol 71, 398-404.
9. Bruick, R. K. (2000). Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci U S A 97, 9082-9087.
10. Buddaert, W., van Reeth, K. & Pensaert, M. (1998). In vivo and in vitro interferon (IFN) studies with the porcine reproductive and respiratory syndrome virus (PRRSV). Adv Exp Med Biol 440, 461-467.
11. Chang, H. W., Jeng, C. R., Liu, J. J., Lin, T. L., Chang, C. C., Chia, M. Y., Tsai, Y. C. & Pang, V. F. (2005). Reduction of porcine reproductive and respiratory syndrome virus (PRRSV) infection in swine alveolar macrophages by porcine circovirus 2 (PCV2)-induced interferon-α. Vet Microbiol 108, 167-177.
12. Charemtantanakul, W., Platt, R. & Roth, J. A. (2006). Effects of porcine reproductive and respiratory syndrome virus-infected antigen-presenting cells on T cell activation and antiviral cytokine production. Viral Immunol 19, 646-661.
13. Costers, S., Delputte, P. L. & Nauwynck, H. J. (2006). Porcine reproductive and respiratory syndrome virus-infected alveolar macrophages contain no detectable levels of viral proteins in their plasma membrane and are protected against antibody-dependent, complement-mediated cell lysis. J Gen Virol 87, 2341-2351.
14. Delputte, P. L. & Nauwynck, H. J. (2004). Porcine arterivirus infection of alveolar macrophages is mediated by sialic acid on the virus. J Virol 78, 8094-8101.
15. Delputte, P. L., van Breedam, W., Barbé, F., van Reeth, K. & Nauwynck, H. J. (2007). IFN-α treatment enhances porcine arterivirus infection of monocytes via upregulation of the porcine arterivirus receptor sialoadhesin. J Interferon Cytokine Res 27, 757-766.
16. Dennis, G., Jr, Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C. & Lempicki, R. A. (2003). DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4, R60.
17. Díaz, I., Darwich, L., Pappaterra, G., Pujols, J. & Mateu, E. (2005). Immune responses of pigs after experimental infection with a European strain of porcine reproductive and respiratory syndrome virus. J Gen Virol 86, 1943-1951.
18. Dixit, V. M., Green, S., Sarma, V., Holzman, L. B., Wolf, F. W., O'Rourke, K., Ward, P. A., Prochownik, E. V. & Marks, R. M. (1990). Tumor necrosis factor-α induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin. J Biol Chem 265, 2973-2978.
19. Duan, X., Nauwynck, H. J. & Pensaert, M. B. (1997a). Effects of origin and state of differentiation and activation of monocytes/ macrophages on their susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV). Arch Virol 142, 2483-2497.
20. Duan, X., Nauwynck, H. J. & Pensaert, M. B. (1997b). Virus quantification and identification of cellular targets in the lungs and lymphoid tissues of pigs at different time intervals after inoculation with porcine reproductive and respiratory syndrome virus (PRRSV). Vet Microbiol 56, 9-19.
21. Fickenscher, H., Hor, S., Kupers, H., Knappe, A., Wittmann, S. & Sticht, H. (2002). The interleukin-10 family of cytokines. Trends Immunol 23, 89-96.
22. Flores-Mendoza, L., Silva-Campa, E., Reséndiz, M., Osorio, F. A. & Hernández, J. (2008). Porcine reproductive and respiratory syndrome virus (PRRSV) infects mature porcine dendritic cells and up-regulates IL-10 production. Clin Vaccine Immunol 15, 720-725.
23. Genini, S., Malinverni, R., Delputte, P. L., Fiorentini, S., Stella, A., Botti, S., Nauwynck, H. J. & Giuffra, E. (2008). Gene expression profiling of porcine alveolar macrophages after antibody-mediated crosslinking of sialoadhesin (Sn, Siglec-1). J Recept Signal Transduct Res 28, 185-243.
24. Halbur, P. G. (2001). Emerging and recurring diseases in growing pigs. In Animal Health, Biotechnology and Trade, Annual Meeting of the National Institute for Animal Agriculture Proceedings, Colorado Springs, CO, USA, 3 April 2001. http://animalagriculture.com/Proceedings/ 2001%20Proc/Halbur.htm.
25. Han, E. S., Wu, Y., McCarter, R., Nelson, J. F., Richardson, A. & Hilsenbeck, S. G. (2004). Reproducibility, sources of variability, pooling, and sample size: important considerations for the design of high-density oligonucleotide array experiments. J Gerontol A Biol Sci Med Sci 59, 306-315.
26. Jenner, R. G. & Young, R. A. (2005). Insights into host responses against pathogens from transcriptional profiling. Nat Rev Microbiol 3, 281-294.
27. Kim, T. S., Benfield, D. A. & Rowland, R. R. (2002). Porcine reproductive and respiratory syndrome virus-induced cell death exhibits features consistent with a nontypical form of apoptosis. Virus Res 85, 133-140.
28. Kubo, A., Minamino, N., Isumi, Y., Katafuchi, T., Kangawa, K., Dohi, K. & Matsuo, H. (1998). Production of adrenomedullin in macrophage cell line and peritoneal macrophage. J Biol Chem 273, 16730-16738.
29. Lamm, G. M., Nicol, S. M., Fuller-Pace, F. V. & Lamond, A. I. (1996). p72: a human nuclear DEAD box protein highly related to p68. Nucleic Acids Res 24, 3739-3747.
30. Lara-Pezzi, E., Pezzi, N., Prieto, I., Barthelemy, I., Carreiro, C., Martínez, A., Maldonado-Rodríguez, A., López-Cabrera, M. & Barbero, J. L. (2004). Evidence of a transcriptional co-activator function of cohesin STAG/SA/Scc3. J Biol Chem 279, 6553-6559.
31. Lee, E. G., Boone, D. L., Chai, S., Libby, S. L., Chien, M., Lodolce, J. P. & Ma, A. (2000). Failure to regulate TNF-induced NF-κB and cell death responses in A20-deficient mice. Science 289, 2350-2354.
32. Lee, C., Bachand, A., Murtaugh, M. P. & Yoo, D. (2004). Differential host cell gene expression regulated by the porcine reproductive and respiratory syndrome virus GP4 and GP5 glycoproteins. Vet Immunol Immunopathol 102, 189-198.
33. Lewis, C. R., Ait-Ali, T., Clapperton, M., Archibald, A. L. & Bishop, S. (2007). Genetic perspectives on host responses to porcine reproductive and respiratory syndrome (PRRS). Viral Immunol 20, 343-358.
34. Li, H. L., Wang, A. B., Zhang, R., Wei, Y. S., Chen, H. Z., She, Z. G., Huang, Y., Liu, D. P. & Liang, C. C. (2006). A20 inhibits oxidized low-density lipoprotein-induced apoptosis through negative Fas/ Fas ligand-dependent activation of caspase-8 and mitochondrial pathways in murine RAW264.7 macrophages. J Cell Physiol 208, 307-318.
35. Lopez, O. J. & Osorio, F. A. (2004). Role of neutralizing antibodies in PRRSV protective immunity. Vet Immunol Immunopathol 102, 155-163.
36. Loving, C. L., Brockmeier, S. L. & Sacco, R. E. (2007). Differential type I interferon activation and susceptibility of dendritic cell populations to porcine arterivirus. Immunology 120, 217-229.
37. Maiese, K., Vincent, A., Lin, S.-H. & Shaw, T. (2000). Group I and group III metabotropic glutamate receptor subtypes provide enhanced neuroprotection. J Neurosci Res 62, 257-272.
38. Mateu, E. & Diaz, I. (2007). The challenge of PRRS immunology. Vet J 177, 345-351.
39. Meier, W. A., Galeota, J., Osorio, F. A., Husmann, R. J., Schnitzlein, W. M. & Zuckermann, F. A. (2003). Gradual development of the interferon-γ response of swine to porcine reproductive and respiratory-syndrome virus infection or vaccination. Virology 309, 18-31.
40. Mengeling, W. L. & Lager, K. M. (2000). A brief review of procedures and potential problems associated with the diagnosis of porcine reproductive and respiratory syndrome. Vet Res 31, 61-69.
41. Miller, L. C. & Fox, J. M. (2004). Apoptosis and porcine reproductive and respiratory syndrome virus. Vet Immunol Immunopathol 102, 131-142.
42. Miller, L. C., Laegreid, W. W., Bono, J. L., Chitko-McKown, C. G. & Fox, J. M. (2004). Interferon type I response in porcine reproductive and respiratory syndrome virus-infected MARC-145 cells. Arch Virol 149, 2453-2463.
43. Moore, K. W., de Waal Malefyt, R., Coffman, R. L. & O'Garra, A. (2001). Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19, 683-765.
44. Moore, C. B., Bergstralh, D. T., Duncan, J. A., Lei, Y., Morrison, T. E., Zimmermann, A. G., Accavitti-Loper, M. A., Madden, V. J., Sun, L. & other authors (2008). NLRX1 is a regulator of mitochondrial antiviral immunity. Nature 451, 573-577.
45. Murtaugh, M. P., Xiao, Z. & Zuckermann, F. (2002). Immunological responses of swine to porcine reproductive and respiratory syndrome virus infection. Viral Immunol 15, 533-547.
46. Neumann, E. J., Kliebenstein, J. B., Johnson, C. D., Mabry, J. W., Bush, E. J., Seitzinger, A. H., Green, A. L. & Zimmerman, J. J. (2005). Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States. J Am Vet Med Assoc 227, 385-392.
47. Nodelijk, G. (2002). Porcine reproductive and respiratory syndrome (PRRS) with special reference to clinical aspects and diagnosis. A review. Vet Q 24, 95-100.
48. Onose, A., Hashimoto, S., Hayashi, S., Maruoka, S., Kumasawa, F., Mizumura, K., Jibiki, I., Matsumoto, K., Gon, Y. & other authors (2006). An inhibitory effect of A20 on NF-κB activation in airway epithelium upon influenza virus infection. Eur J Pharmacol 541, 198-204.
49. Overend, C., Mitchell, R., He, D., Rompato, G., Grubman, M. J. & Garmendia, A. E. (2007). Recombinant swine beta interferon protects swine alveolar macrophages and MARC-145 cells from infection with Porcine reproductive and respiratory syndrome virus. J Gen Virol 88, 925-931.
50. Prag, S. & Adams, J. C. (2003). Molecular phylogeny of the kelch-repeat superfamily reveals an expansion of BTB/kelch proteins in animals. BMC Bioinform 4, 42.
51. Qin, Y. J., Zhang, Z. L., Yu, L. Y., He, J. W., Hou, Y. N., Liu, T. J., Wu, J. C., Wu, S. H. & Guo, L. H. (2006). A20 overexpression under control of mouse osteocalcin promoter in MC3T3-E1 cells inhibited tumor necrosis factor-α-induced apoptosis. Acta Pharmacol Sin 27, 1231-1237.
52. Redpath, S., Ghazal, P. & Gascoigne, N. R. (2001). Hijacking and exploitation of IL-10 by intracellular pathogens. Trends Microbiol 9, 86-92.
53. Rossow, K. D., Collins, J. E., Goyal, S. M., Nelson, E. A., Christopher-Hennings, J. & Benfield, D. A. (1995). Pathogenesis of porcine reproductive and respiratory syndrome virus infection in gnotobiotic pigs. Vet Pathol 32, 361-373.
54. Rowland, R. R., Lawson, S., Rossow, K. & Benfield, D. A. (2003). Lymphoid tissue tropism of porcine reproductive and respiratory syndrome virus replication during persistent infection of pigs originally exposed to virus in utero. Vet Microbiol 96, 219-235.
55. Royaee, A. R., Husmann, R. J., Dawson, H. D., Calzada-Nova, G., Schnitzlein, W. M., Zuckermann, F. A. & Lunney, J. K. (2004). Deciphering the involvement of innate immune factors in the development of the host response to PRRSV vaccination. Vet Immunol Immunopathol 102, 199-216.
56. Saegusa, K., Yotsumoto, S., Kato, S. & Aramaki, Y. (2007). Phosphatidylinositol 3-kinase-mediated regulation of IL-10 and IL-12 production in macrophages stimulated with CpG oligodeoxynucleotide. Mol Immunol 44, 1323-1330.
57. Shen, G., Xu, C., Hu, R., Jain, M. R., Nair, S., Lin, W., Yang, C. S., Chan, J. Y. & Kong, A. N. (2005). Comparison of (-)-epigallocatechin-3-gallate elicited liver and small intestine gene expression profiles between C57BL/6J mice and C57BL/6J/Nrf2 (-/-) mice. Pharm Res 22, 1805-1820.
58. Sieg, S., King, C., Huang, Y. & Kaplan, D. (1996). The role of interleukin-10 in the inhibition of T-cell proliferation and apoptosis mediated by parainfluenza virus type 3. J Virol 70, 4845-4848.
59. Sirinarumitr, T., Zhang, Y., Kluge, J. P., Halbur, P. G. & Paul, P. S. (1998). A pneumo-virulent United States isolate of porcine reproductive and respiratory syndrome virus induces apoptosis in bystander cells both in vitro and in vivo. J Gen Virol 79, 2989-2995.
60. Snijder, E. J. & Meulenberg, J. J. M. (1998). The molecular biology of arteriviruses. J Gen Virol 79, 961-979.
61. Suradhat, S. & Thanawongnuwech, R. (2003). Upregulation of interleukin-10 gene expression in the leukocytes of pigs infected with porcine reproductive and respiratory syndrome virus. J Gen Virol 84, 2755-2760.
62. Suradhat, S., Thanawongnuwech, R. & Poovorawan, Y. (2003). Upregulation of IL-10 gene expression in porcine peripheral blood mononuclear cells by porcine reproductive and respiratory syndrome virus. J Gen Virol 84, 453-459.
63. Sutherland, M. A., Niekamp, S. R., Johnson, R. W., van Alstine, W. G. & Salak-Johnson, J. L. (2007). Heat and social rank impact behavior and physiology of PRRS-virus-infected pigs. Physiol Behav 90, 73-81.
64. Tanaka, N., Sato, M., Lamphier, M. S., Nozawa, H., Oda, E., Noguchi, S., Schreiber, R. D., Tsujimoto, Y. & Taniguchi, T. (1998). Type I interferons are essential mediators of apoptotic death in virally infected cells. Genes Cells 3, 29-37.
65. Teifke, J. P., Dauber, M., Fichtner, D., Lenk, M., Polster, U., Weiland, E. & Beyer, J. (2001). Detection of European porcine reproductive and respiratory syndrome virus in porcine alveolar macrophages by two-colour immunofluorescence and in-situ hybridization-immunohistochemistry double labelling. J Comp Pathol 124, 238-245.
66. Thanawongnuwech, R. & Thacker, E. L. (2003). Interleukin-10, interleukin-12, and interferon-γ levels in the respiratory tract following mycoplasma hyopneumoniae and PRRSV infection in pigs. Viral Immunol 16, 357-367.
67. Thanawongnuwech, R., Thacker, B., Halbur, P. & Thacker, E. L. (2004). Increased production of proinflammatory cytokines following infection with porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae. Clin Diagn Lab Immunol 11, 901-908.
68. Tsai, E. Y., Yie, J., Thanos, D. & Goldfeld, A. E. (1996). Cell-type-specific regulation of the human tumor necrosis factor α gene in B cells and T cells by NFATp and ATF-2/JUN. Mol Cell Biol 16, 5232-5244.
69. Tsai, S., Cassady, J. P., Freking, B. A., Nonneman, D. J., Rohrer, G. A. & Piedrahita, J. A. (2006). Annotation of the Affymetrix porcine genome microarray. Anim Genet 37, 423-424.
70. Uzan, B., Ea, H. K., Launay, J. M., Garel, J. M., Champy, R., Cressent, M. & Lioté, F. (2006). A critical role for adrenomedullin-calcitonin receptor-like receptor in regulating rheumatoid fibroblast-like synoviocyte apoptosis. J Immunol 176, 5548-5558.
71. van Reeth, K., Labarque, G., Nauwynck, H. & Pensaert, M. (1999). Differential production of proinflammatory cytokines in the pig lung during different respiratory virus infections: correlations with pathogenicity. Res Vet Sci 67, 47-52.
72. Voicu, I. L., Silim, A., Morin, M. & Elazhary, M. A. (1994). Interaction of porcine reproductive and respiratory syndrome virus with swine monocytes. Vet Rec 134, 422-423.
73. Wang, X., Eaton, M., Mayer, M., Li, H., He, D., Nelson, E. & Christopher-Hennings, J. (2007). Porcine reproductive and respiratory syndrome virus productively infects monocyte-derived dendritic cells and compromises their antigen-presenting ability. Arch Virol 152, 289-303.
74. Weidman, M. K., Sharma, R., Raychaudhuri, S., Kundu, P., Tsai, W. & Dasgupta, A. (2003). The interaction of cytoplasmic RNA viruses with the nucleus. Virus Res 95, 75-85.
75. Wensvoort, G., Terpstra, C., Pol, J.M. A., ter Laak, E. A., Bloemraad, M., de Kluyver, E. P., Kragten, C., van Buiten, L., den Besten, A. & other authors (1991). Mystery swine disease in The Netherlands: the isolation of the Lelystad virus. Vet Q 13, 121-130.
76. Wills, R. W., Doster, A. R., Galeota, J. A., Sur, J. H. & Osorio, F. A. (2003). Duration of infection and proportion of pigs persistently infected with porcine reproductive and respiratory syndrome virus. J Clin Microbiol 41, 58-62.
77. Xiao, Z., Batista, L., Dee, S., Halbur, P. & Murtaugh, M. P. (2004). The level of virus-specific T-cell and macrophage recruitment in porcine reproductive and respiratory syndrome virus infection in pigs is independent of virus load. J Virol 78, 5923-5933.
78. Xu, L. G., Wang, Y. Y., Han, K. J., Li, L. Y., Zhai, Z. & Shu, H. B. (2005). VISA is an adapter protein required for virus-triggered IFN-β signaling. Mol Cell 19, 727-740.
79. Yang, Z., Mosser, D. M. & Zhang, X. (2007). Activation of the MAPK, ERK, following Leishmania amazonensis infection of macrophages. J Immunol 178, 1077-1085.
80. Yasuda, J., Tsuchiya, A., Yamada, T., Sakamoto, M., Sekiya, T. & Hirohashi, S. (2003). Nemo-like kinase induces apoptosis in DLD-1 human colon cancer cells. Biochem Biophys Res Commun 308, 227-233.
81. Yin, H., Chao, L. & Chao, J. (2004). Adrenomedullin protects against myocardial apoptosis after ischemia/reperfusion through activation of Akt-GSK signaling. Hypertension 43, 109-116.
82. Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S. & Fujita, T. (2004). The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5, 730-737.
83. Zhang, X., Shin, J., Molitor, T. W., Schook, L. B. & Rutherford, M. S. (1999). Molecular responses of macrophages to porcine reproductive and respiratory syndrome virus infection. Virology 262, 152-162.
84. Zhang, X., Wang, C., Schook, L. B., Hawken, R. J. & Rutherford, M. S. (2000). An RNA helicase, RHIV-1, induced by porcine reproductive and respiratory syndrome virus (PRRSV) is mapped on porcine chromosome 10q13. Microb Pathog 28, 267-278.
85. Zhou, J. H., Broussard, S. R., Strle, K., Freund, G. G., Johnson, R. W., Dantzer, R. & Kelley, K. W. (2001). IL-10 inhibits apoptosis of promyeloid cells by activating insulin receptor substrate-2 and phosphatidylinositol 3′-kinase. J Immunol 167, 4436-4442.