title: Interleukin 10 and TNFalpha synergistically enhance the expression of the G protein-coupled formylpeptide receptor 2 in microglia.
abstract: Microglia are important participants in inflammatory responses in the central nervous system. We previously observed that tumor necrosis factor alpha (TNFalpha) induces the expression of the formylpeptide receptor mFPR2 on microglial cells. This chemoattractant receptor mediates microglial cell chemotaxis in response to a variety of peptides, including amyloid beta peptide (Abeta(42)), a major pathogenic factor in Alzheimer's disease (AD). In search for agents that regulate microglial activation, we unexpectedly found that IL-10 enhanced the expression of mFPR2 on TNFalpha-activated microglia. This was associated with a markedly increased microglial chemotaxis to Abeta(42) and its endocytosis via mFPR2. Mechanistic studies revealed that the synergistic effect of IL-10 on TNFalpha-induction of mFPR2 in microglia was dependent on activation of p38 MAPK. Our results suggest that IL-10 may affect the pathogenic process of AD by up-regulating mFPR2 and thus favoring the recognition and internalization of Abeta(42) by activated microglial cells.
authors.affiliation: Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA. piribarr@mail.fcq.unc.edu.ar
authors.forename: Pablo
authors.initials: P
authors.lastname: Iribarren
authors.forename: Keqiang
authors.initials: K
authors.lastname: Chen
authors.forename: Wanghua
authors.initials: W
authors.lastname: Gong
authors.forename: Edward H
authors.initials: EH
authors.lastname: Cho
authors.forename: Stephen
authors.initials: S
authors.lastname: Lockett
authors.forename: Badarch
authors.initials: B
authors.lastname: Uranchimeg
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000493:pharmacokinetics; D000818:Animals; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000502:physiology; D010446:Peptide Fragments / Q000493:pharmacokinetics; D044042:Receptors, Formyl Peptide / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D044042:Receptors, Formyl Peptide; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); C481578:formyl peptide receptor 2, mouse; D016753:Interleukin-10; D048051:p38 Mitogen-Activated Protein Kinases