Regulation of macrophage IL-10 production postinjury via beta2 integrin signaling and the P38 MAP kinase pathway.

Martin G. Schwacha, Irshad H. Chaudry, Michelle Alexander

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Although LPS receptor (CD14) signaling is mediated in part by beta2 integrins, the role of beta2 integrins in macrophage LPS signaling postinjury remains unknown. To study this, splenic macrophages were isolated from mice 7 days postburn, and inflammatory mediator production was determined. Macrophages isolated from injured mice produced higher levels of PGE2, TNF-alpha, IL-6, and IL-10 and lower levels of IL-12 in response to LPS stimulation than did cells from sham-treated mice. Blockade of beta2 integrin signaling by addition of antibodies against the CD11b (alphaCD11b) to the cultures increased IL-10 production by macrophages from injured mice without affecting other mediators. In contrast, sham macrophage responses to LPS were unaffected by alphaCD11b. Inhibition of p38 MAP kinase activity attenuated IL-10 production and abrogated the enhanced IL-10 response induced by alphaCD11b, whereas ERK 1/2 inhibition had no effect. Burn injury was associated with increased levels of total and phosphorylated p38 MAP kinase. These findings indicate that LPS signaling via beta2 integrins acts to attenuate the exaggerated induction of IL-10 by macrophages postinjury. Moreover, this effect of beta2 integrin signaling postinjury appears to be downstream of the p38 MAP kinase pathway and is independent of other markers of macrophage hyperactivity.

Original languageEnglish (US)
Pages (from-to)529-535
Number of pages7
JournalShock (Augusta, Ga.)
Issue number6
StatePublished - Dec 2003
Externally publishedYes

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine


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