Interleukin 10 and TNFalpha Synergistically Enhance The Expression of The G-Protein Coupled Formylpeptide Receptor 2 in Microglia

PABLO IRIBARREN, KEQIANG CHEN, WANGHUA GONG, EDWARD H. CHO, STEPHEN LOCKETT, BADARCH URANCHIMEG, JAVIER SORIA, DANIELA ARROYO, CLELIA M. RIERA AND JI MING WANG.

Rio de Janeiro, Brasil

Congreso; 13th International Congress of Immunology; 2007

International Union of Immunological Societies

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.