Stat3 in resident macrophages as a repressor protein of inflammatory response

Akihiro Matsukawa, Shinji Kudo, Takako Maeda, Kousuke Numata, Hiroyuki Watanabe, Kiyoshi Takeda, Shizuo Akira, Takaaki Ito

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78 Citations (Scopus)

Abstract

Inflammation is counterbalanced by anti-inflammatory cytokines such as IL-10, in which Stat3 mediates the signaling pathway. In this study, we demonstrate that resident macrophages, but not other cell types, are important targets of IL-10 in a murine model of acute peritonitis. Injection of thioglycollate i.p. induced a considerable number of neutrophils and macrophages in the peritoneum, which was significantly augmented in mice with a cell-type specific disruption of the Stat3 gene in macrophages and neutrophils (LysMcre/Stat3flox/- mice). The augmented leukocyte infiltration was accompanied by increased peritoneal levels of TNF-α, MIP-2, KC chemokine (KC), and MCP-1/CCL2. Stat3 was tyrosine phosphorylated in peritoneal resident macrophages as well as infiltrating leukocytes in the littermate controls, suggesting that Stat3 in either or both of these cells might play a regulatory role in inflammation. The peritoneal levels of TNF-α, MIP-2, KC, and MCP-1 were similarly elevated in LysMcre/Stat3flox/- mice rendered leukopenic by cyclophosphamide treatment as compared with the controls. Adoptive transfer of resident macrophages from LysMcre/Stat3flox/- mice into the control littermates resulted in increases in the peritoneal level of TNF-α, MIP-2, KC, and MCP-1 after i.p. injection of thioglycollate. Under these conditions, control littermates harboring LysMcre/Stat3flox/- macrophages exhibited an augmented leukocyte infiltration relative to those received control macrophages. Taken together, these data provide evidence that resident macrophages, but not other cell types, play a regulatory role in inflammation through a Stat3 signaling pathway. Stat3 in resident macrophages appears to function as a repressor protein in this model of acute inflammation.

Original languageEnglish
Pages (from-to)3354-3359
Number of pages6
JournalJournal of Immunology
Volume175
Issue number5
DOIs
Publication statusPublished - Sep 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Matsukawa, A., Kudo, S., Maeda, T., Numata, K., Watanabe, H., Takeda, K., Akira, S., & Ito, T. (2005). Stat3 in resident macrophages as a repressor protein of inflammatory response. Journal of Immunology, 175(5), 3354-3359. https://doi.org/10.4049/jimmunol.175.5.3354