C5a controls TLR-induced IL-10 and IL-12 production independent of phosphoinositide 3-kinase.

Abstract:

:The complement system is a classic central player in innate immunity. Most pathogens activate both complement and the toll-like receptor (TLR) pathway. Therefore, to provide a more comprehensive understanding of innate immunity, it is important to understand the crosstalk between these two systems. Mouse macrophages produce IL-12 and IL-10 in response to TLR ligands such as LPS, CpG, Poly I:C and Malp2. The TLR-induced IL-12 production was decreased, while that of IL-10 was increased by concurrent stimulation with a complement fragment C5a. Pharmacological studies have suggested that C5a regulates TLR4-induced IL-12 production in a phosphoinositide 3-kinase (PI3K)-dependent mechanism. In the present study, however, we found that the C5a-mediated changes can be observed in macrophages from mice lacking PI3K p85α or PI3K p110γ. The result indicates that the C5a action is PI3K-independent; neither class IA nor class IB PI3K subtype is involved in this regulation. The actions of C5a were sensitive to pertussis toxin and PD98059, suggesting a role of G protein-mediated activation of the Erk1/2 pathway.

journal_name

J Biochem

journal_title

Journal of biochemistry

authors

Okazaki N,Hazeki K,Izumi T,Nigorikawa K,Hazeki O

doi

10.1093/jb/mvq136

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

265-74

issue

3

eissn

0021-924X

issn

1756-2651

pii

mvq136

journal_volume

149

pub_type

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