Interleukin 10 and TNFalpha synergistically enhance the expression of the G protein-coupled formylpeptide receptor 2 in microglia.
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.
Iribarren
Pablo
P
Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA. piribarr@mail.fcq.unc.edu.ar
Chen
Keqiang
K
Gong
Wanghua
W
Cho
Edward H
EH
Lockett
Stephen
S
Uranchimeg
Badarch
B
Wang
Ji Ming
JM
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
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