Pivotal role of signal transducer and activator of transcription (Stat)4 and Stat6 in the innate immune response during sepsis

A. Matsukawa, Mark Kaplan, C. M. Hogaboam, N. W. Lukacs, S. L. Kunkel

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Signal transducer and activator of transcription (Stat)4 and Stat6 are transcription factors that provide type 1 and type 2 response, respectively. Here, we explored the role of Stat4 and Stat6 in innate immunity during septic peritonitis. Stat4-/- and Stat6-/- mice were resistant to the lethality compared with wild-type (WT) mice. At the mechanistic level, bacterial levels in Stat6-/- mice were much lower than in WT mice, which was associated with increased peritoneal levels of interleukin (IL)-12, tumor necrosis factor (TNF)-α macrophage-derived chemokine (MDC), and C10, known to enhance bacterial clearance. In Stat4-/- mice, hepatic inflammation and injury during sepsis were significantly ameliorated without affecting local responses. This event was associated with increased hepatic levels of IL-10 and IL-13, while decreasing those of macrophage inflammatory protein (MIP)-2 and KC. Sepsis-induced renal injury was also abrogated in Stat4-/- mice, which was accompanied by decreased renal levels of MIP-2 and KC without altering IL-10 and IL-13 levels. Thus, Stat6-/- and Stat4-/- mice appeared to be resistant to septic peritonitis by enhancing local bacterial clearance and modulating systemic organ damage, respectively, via balancing cytokine responses. These results clearly highlight an important role of local type 1 and systemic type 2 cytokine response in protective immunity during sepsis, which can be regulated by Stat proteins.

Original languageEnglish (US)
Pages (from-to)679-688
Number of pages10
JournalJournal of Experimental Medicine
Volume193
Issue number6
DOIs
StatePublished - Mar 19 2001
Externally publishedYes

Fingerprint

STAT4 Transcription Factor
Innate Immunity
Sepsis
Chemokine CXCL2
Interleukin-13
Peritonitis
Interleukin-10
Chemokine CCL22
STAT Transcription Factors
Cytokines
Kidney
Liver
Wounds and Injuries
Interleukin-12
Immunity
Transcription Factors
Tumor Necrosis Factor-alpha
Inflammation

Keywords

  • Bacteria
  • Cytokines
  • Innate immunity
  • Multiple organ failure
  • Sepsis

ASJC Scopus subject areas

  • Immunology

Cite this

Pivotal role of signal transducer and activator of transcription (Stat)4 and Stat6 in the innate immune response during sepsis. / Matsukawa, A.; Kaplan, Mark; Hogaboam, C. M.; Lukacs, N. W.; Kunkel, S. L.

In: Journal of Experimental Medicine, Vol. 193, No. 6, 19.03.2001, p. 679-688.

Research output: Contribution to journalArticle

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