Role of STK in mouse liver macrophage and endothelial cell responsiveness during acute endotoxemia

Debra L. Laskin, Li Chen, Pamela A. Hankey, Jeffrey D. Laskin

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Acute endotoxemia is associated with excessive production of proinflammatory mediators by hepatic macrophages and endothelial cells, which have been implicated in liver injury and sepsis. In these studies, we analyzed the role of MSP and its receptor STK in regulating the activity of these cells. Acute endotoxemia, induced by administration of LPS (3 mg/kg) to mice, resulted in increased expression of STK mRNA and protein in liver macrophages and endothelial cells, an effect that was dependent on TLR-4. This was correlated with decreased MSP and increased pro-MSP in serum. In Kupffer cells, but not endothelial cells, MSP suppressed LPS-induced NOS-2 expression, with no effect on COX-2. LPS treatment of mice caused a rapid (within 3 h) increase in the proinflammatory proteins NOS-2, IL-1β, and TNF-α, as well as TREM-1 and TREM-3 and the anti-inflammatory cytokine IL-10 in liver macropahges and endothelial cells. Whereas LPS-induced expression of proinflammatory proteins was unchanged in STK-/- mice, IL-10 expression was reduced significantly. Enzymes mediating eicosanoid biosynthesis including COX-2 and mPGES-1 also increased in macrophages and endothelial cells after LPS administration. In STK-/- mice treated with LPS, mPGES-1 expression increased, although COX-2 expression was reduced. LPS-induced up-regulation of SOD was also reduced in STK-/- mice in liver macrophages and endothelial cells. These data suggest that MSP/STK signaling plays a role in up-regulating macrophage and endothelial cell anti-inflammatory activity during hepatic inflammatory responses. This may be important in protecting the liver from tissue injury.

Original languageEnglish (US)
Pages (from-to)373-382
Number of pages10
JournalJournal of Leukocyte Biology
Volume88
Issue number2
DOIs
StatePublished - Aug 2010

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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