Apoptotic cells inhibit LPS-induced cytokine and chemokine production and IFN responses in macrophages. Academic Article uri icon

Overview

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.

publication date

  • January 8, 2007

Research

keywords

  • Apoptosis
  • Chemokines
  • Cytokines
  • Interferon Type I
  • Interferon-gamma
  • Lipopolysaccharides
  • Macrophages, Peritoneal

Identity

PubMed Central ID

  • PMC2736914

Scopus Document Identifier

  • 33847703719

Digital Object Identifier (DOI)

  • 10.1016/j.humimm.2006.12.008

PubMed ID

  • 17349870

Additional Document Info

volume

  • 68

issue

  • 3