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Apoptotic cells inhibit LPS-induced cytokine and chemokine production and IFN responses in macrophages.

Abstract：

:Apoptosis is a critical process in tissue homeostasis and results in immediate removal of the dying cell by professional phagocytes such as macrophages and dendritic cells. Phagocytosis of apoptotic cells actively suppresses production of proinflammatory growth factors and cytokines. Impaired phagocytosis of apoptotic cells has been implicated in the pathogenesis of chronic inflammatory and autoimmune diseases. In this study we found that, in addition to suppressing lipopolysaccharide (LPS)-induced production of TNF-alpha and IL-6, phagocytosis of apoptotic cells by macrophages suppressed production of the chemokine CXCL10 that is activated by LPS-induced autocrine-acting type I IFNs. Inhibition of cytokine and chemokine production was not universally affected because LPS-induced production of IL-10 and IL-8 was not significantly affected. Apoptotic cells had minimal effects on LPS-induced activation of NF-kappaB and MAPKs, but induced expression of SOCS proteins and substantially suppressed induction of CXCL10 expression by IFN-alpha. In addition to suppressing LPS responses, apoptotic cells inhibited macrophage responses to another major macrophage activator IFN-gamma by attenuating IFN-gamma-induced STAT1 activation and downstream gene expression. These results identify suppressive effects of apoptotic cells on signal transduction, and extend our understanding of the anti-inflammatory effects of apoptotic cells to include suppression of Jak-STAT signaling.

journal_name

Hum Immunol

journal_title

Human immunology

authors

Tassiulas I,Park-Min KH,Hu Y,Kellerman L,Mevorach D,Ivashkiv LB

doi

10.1016/j.humimm.2006.12.008

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

156-64

issue

3

eissn

0198-8859

issn

1879-1166

pii

S0198-8859(06)00614-8

journal_volume

68

pub_type

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