title: IL-4 down-regulates lipopolysaccharide-induced formyl peptide receptor 2 in murine microglial cells by inhibiting the activation of mitogen-activated protein kinases.
abstract: Microglial cells actively participate in proinflammatory responses in the CNS. Upon stimulation with the bacterial LPS, microglial cells express a functional formyl peptide receptor 2 which mediates the chemotactic and activating effects of a variety of polypeptide agonists including amyloid beta (Abeta(1-42)), a critical pathogenic agent in Alzheimer's disease. In the present study, we found that LPS-induced expression and function of formyl peptide receptor 2 in microglial cells was markedly inhibited by IL-4, a Th2-type cytokine. Our effort to elucidate the mechanistic basis revealed that IL-4 attenuated LPS-stimulated activation of NF-kappaB, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase, and the effect of IL-4 was associated with a phosphoinositide 3-kinase pathway-dependent increase in serine/threonine phosphatase activity. These results suggest that IL-4 may play an important role in the maintenance of homeostasis of CNS and in the regulation of the disease process characterized by microglial activation in response to proinflammatory stimulants.
authors: Laboratory of Molecular Immunoregulation, Lanzhou Military Medical University, Lanzhou, People's Republic of China.
authors: Pablo
authors: P
authors: Iribarren
authors: You-Hong
authors: YH
authors: Cui
authors: Yingying
authors: Y
authors: Le
authors: GuoGuang
authors: G
authors: Ying
authors: Xia
authors: X
authors: Zhang
authors: Wanghua
authors: W
authors: Gong
authors: Ji Ming
authors: JM
authors: Wang
mesh_terms: D051698:Activating Transcription Factor 2; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000276:immunology; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D051698:Activating Transcription Factor 2; D000954:Antigens, Surface; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D020033:Protein Isoforms; D044042:Receptors, Formyl Peptide; D014157:Transcription Factors; C481578:formyl peptide receptor 2, mouse; D015847:Interleukin-4; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases