PGE2 Inhibits IL-10 Production via EP2-Mediated β-Arrestin Signaling in Neuroinflammatory Condition

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• 作者：Chun-Hsien Chu ; Shih-Heng Chen ; Qingshan Wang ; Robert Langenbach…
• 关键词：Microglia ; IL ; 10 ; PGE2 ; COX ; 2 ; EP2 ; β ; arrestin
• 刊名：Molecular Neurobiology
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：52
• 期：1
• 页码：587-600
• 全文大小：636 KB
• 参考文献：1.Merrill JE, Benveniste EN (1996) Cytokines in inflammatory brain lesions: helpful and harmful. Trends Neurosci 19(8):331-38PubMed View Article
  2.Medzhitov R (2008) Origin and physiological roles of inflammation. Nature 454(7203):428-35. doi:10.-038/?nature07201 PubMed View Article
  3.Nathan C (2002) Points of control in inflammation. Nature 420(6917):846-52. doi:10.-038/?nature01320 PubMed View Article
  4.Kielian T (2006) Toll-like receptors in central nervous system glial inflammation and homeostasis. J Neurosci Res 83(5):711-30. doi:10.-002/?jnr.-0767 PubMed Central PubMed View Article
  5.Serhan CN, Chiang N, Van Dyke TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8(5):349-61. doi:10.-038/?nri2294 PubMed Central PubMed View Article
  6.Gao HM, Hong JS (2008) Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol 29(8):357-65PubMed View Article
  7.Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55(5):453-62. doi:10.-002/?glia.-0467 PubMed Central PubMed View Article
  8.Frank-Cannon TC, Alto LT, McAlpine FE, Tansey MG (2009) Does neuroinflammation fan the flame in neurodegenerative diseases? Mol Neurodegener 4:47. doi:10.-186/-750-1326-4-47 PubMed Central PubMed View Article
  9.Strle K, Zhou JH, Shen WH, Broussard SR, Johnson RW, Freund GG, Dantzer R, Kelley KW (2001) Interleukin-10 in the brain. Crit Rev Immunol 21(5):427-49PubMed View Article
  10.Saraiva M, O'Garra A (2010) The regulation of IL-10 production by immune cells. Nat Rev Immunol 10(3):170-81. doi:10.-038/?nri2711 PubMed View Article
  11.Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75(2):263-74PubMed View Article
  12.Heyen JR, Ye S, Finck BN, Johnson RW (2000) Interleukin (IL)-10 inhibits IL-6 production in microglia by preventing activation of NF-kappaB. Brain Res Mol Brain Res 77(1):138-47PubMed View Article
  13.Kremlev SG, Palmer C (2005) Interleukin-10 inhibits endotoxin-induced pro-inflammatory cytokines in microglial cell cultures. J Neuroimmunol 162(1-):71-0. doi:10.-016/?j.?jneuroim.-005.-1.-10 PubMed View Article
  14.Sabat R, Grutz G, Warszawska K, Kirsch S, Witte E, Wolk K, Geginat J (2010) Biology of interleukin-10. Cytokine Growth Factor Rev 21(5):331-44. doi:10.-016/?j.?cytogfr.-010.-9.-02 PubMed View Article
  15.Qian L, Block ML, Wei SJ, Lin CF, Reece J, Pang H, Wilson B, Hong JS, Flood PM (2006) Interleukin-10 protects lipopolysaccharide-induced neurotoxicity in primary midbrain cultures by inhibiting the function of NADPH oxidase. J Pharmacol Exp Ther 319(1):44-2. doi:10.-124/?jpet.-06.-06351 PubMed View Article
  16.Sheng WS, Hu S, Kravitz FH, Peterson PK, Chao CC (1995) Tumor necrosis factor alpha upregulates human microglial cell production of interleukin-10 in vitro. Clin Diagn Lab Immunol 2(5):604-08PubMed Central PubMed
  17.Foey AD, Parry SL, Williams LM, Feldmann M, Foxwell BM, Brennan FM (1998) Regulation of monocyte IL-10 synthesis by endogenous IL-1 and TNF-alpha: role of the p38 and p42/44 mitogen-activated protein kinases. J Immunol 160(2):920-28PubMed
  18.Tone M, Powell MJ, Tone Y, Thompson SA, Waldmann H (2000) IL-10 gene expression is controlled by the transcription factors Sp1 and Sp3. J Immunol 165(1):286-91PubMed View Article
  19.Platzer C, Meisel C, Vogt K, Platzer M, Volk HD (1995) Up-regulation of monocytic IL-10 by tumor necrosis factor-alpha and cAMP elevating drugs. Int Immunol 7(4):517-23PubMed View Article
  20.Harizi H, Gualde N (2006) Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derived inflammatory mediators. Cell Mol Immunol 3(4):271-77PubMed
  21.Aloisi F, De Simone R, Columba-Cabezas S, Levi G (1999) Opposite effects of interferon-gamma and prostaglandin E2 on tumor necrosis factor and interleukin-10 production in microglia: a regulatory loop controlling microglia pro- and anti-inflammatory activities. J Neurosci Res 56(6):571-80PubMed View Article
  22.Seo DR, Kim KY, Lee YB (2004) Interleukin-10 expression in lipopolysaccharide-activated microglia is mediated by extracellular ATP in an autocrine fashion. Neuroreport 15(7):1157-161PubMed View Article
  23.Cheon H, Rho YH, Choi SJ, Lee YH, Song GG, Sohn J, Won NH, Ji JD (2006) Prostaglandin E2 augments IL-10 signaling and function. J Immunol 177(2):1092-100PubMed View Article
  24.Chung EY, Liu J, Homma Y, Zhang Y, Brendolan A, Saggese M, Han J, Silverstein R, Selleri L, Ma X (2007) Interleukin-10 expression in macrophages during phagocytosis of apoptotic cells is mediated by homeodomain proteins Pbx1 and Prep-1. Immunity 27(6):952-64. doi:10.-016/?j.?immuni.-007.-1.-14 PubMed Central PubMed View A
• 作者单位：Chun-Hsien Chu (1)
  Shih-Heng Chen (1)
  Qingshan Wang (1)
  Robert Langenbach (2)
  Hong Li (3)
  Darryl Zeldin (3)
  Shiou-Lan Chen (4)
  Shijun Wang (1) (5)
  Huiming Gao (1) (6)
  Ru-Band Lu (10) (11) (7) (8) (9)
  Jau-Shyong Hong (1)
  
  1. Neuropharmacology Section, National Institutes of Health/National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA
  2. Laboratory of Toxicology and Pharmacology, National Institutes of Health/National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA
  3. Laboratory of Respiratory Biology, National Institutes of Health/National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA
  4. Department of Neurology, School of Medicine, Kaohsiung Medical University, Kaohsiung, 80780, Taiwan
  5. Department of Pathology, University of Washington School of Medicine, HMC Box 359635, 325 9th Ave, Seattle, WA, 98104, USA
  6. Model Animal Research Center and MOE Key Laboratory of Model Animal for Disease Study, Nanjing University, 12 Xuefu Road, Nanjing, Jiangsu, 210061, China
  10. Addiction Research Center, National Cheng Kung University, Tainan, 70101, Taiwan
  11. Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, 138 Sheng-Li Road, Tainan, 70428, Taiwan
  7. Institute of Behavioral Medicine, National Cheng Kung University Hospital, Tainan, 70101, Taiwan
  8. Department of Psychiatry, National Cheng Kung University Hospital, Tainan, 70101, Taiwan
  9. Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan
  
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182

文摘

Regulatory mechanisms of the expression of interleukin-10 (IL-10) in brain inflammatory conditions remain elusive. To address this issue, we used multiple primary brain cell cultures to study the expression of IL-10 in lipopolysaccharide (LPS)-elicited inflammatory conditions. In neuron–glia cultures, LPS triggered well-orchestrated expression of various immune factors in the following order: tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and lastly IL-10, and these inflammatory mediators were mainly produced from microglia. While exogenous application of individual earlier-released pro-inflammatory factors (e.g., TNF-α, IL-1β, or PGE2) failed to induce IL-10 expression, removal of LPS from the cultures showed the requirement of continuing presence of LPS for IL-10 expression. Interestingly, genetic disruption of tnf-α, its receptors tnf-r1/r2, and cox-2 and pharmacological inhibition of COX-2 activity enhanced LPS-induced IL-10 production in microglia, which suggests negative regulation of IL-10 induction by the earlier-released TNF-α and PGE2. Further studies showed that negative regulation of IL-10 production by TNF-α is mediated by PGE2. Mechanistic studies indicated that PGE2-elicited suppression of IL-10 induction was eliminated by genetic disruption of the PGE2 receptor EP2 and was mimicked by the specific agonist for the EP2, butaprost, but not agonists for the other three EP receptors. Inhibition of cAMP-dependent signal transduction failed to affect PGE2-mediated inhibition of IL-10 production, suggesting that a G protein-independent pathway was involved. Indeed, deficiency in β-arrestin-1 or β-arrestin-2 abolished PGE2-elicited suppression of IL-10 production. In conclusion, we have demonstrated that COX-2-derived PGE2 inhibits IL-10 expression in brain microglia through a novel EP2- and β-arrestin-dependent signaling pathway.