Blockade of p38 mitogen-activated protein kinase pathway ameliorates delayed intestinal transit in burned rats

Hua Tian Gan, Pankaj J. Pasricha, Jiande D.Z. Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Burn injury has been shown to impair intestinal transit. p38 mitogen-activated protein kinase (MAPK) has been shown to be involved in the production of proinflammatory mediators such as interleukin (IL)-1β, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The aims of this study were to investigate the effects of SB203580, a specific p38 MAPK inhibitor, on intestinal transit and to elucidate its possible mechanism. Methods: Burn rats and sham rats were divided into 4 groups: saline, S-methylisothiourea (a selective iNOS inhibitor), nimesulide (a selective COX-2 inhibitor), or SB203580. Intestinal transit was measured using phenol red and assessed using the geometric center. The protein or gene expression of NOS, COX-2, and IL-1β were measured by real-time reverse-transcription polymerase chain reaction or Western blot analysis. p38 MAPK activity or myeloperoxidase (MPO) activity was determined by using the p38 MAPK assay kit or MPO assay kit. Results: Intestinal transit was delayed significantly with burn injury, improved significantly with S-methylisothiourea and nimesulide, but almost completely normalized with SB203580. p38 MAPK activity, MPO activity, iNOS, COX-2, and IL-1β protein or gene expression increased markedly after burn injury. SB203580 inhibited p38 MAPK and MPO activity, and reduced iNOS, COX-2, and IL-1β protein or gene expression. Conclusions: Burn-induced delayed intestinal transit is associated with the p38 MAPK pathway. Inhibition of the p38 MAPK pathway ameliorates delayed intestinal transit, at least in part, by inhibiting iNOS, COX-2, and IL-1β expression. Thus, p38 MAPK could represent a novel target for therapy of gut dysmotility after burn injury.

Original languageEnglish (US)
Pages (from-to)530-537
Number of pages8
JournalAmerican journal of surgery
Volume193
Issue number4
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

Keywords

  • Burn
  • Cyclooxygenase-2 (COX-2)
  • Intestinal transit
  • Nitric oxide synthase (iNOS)
  • p38 MAPK

ASJC Scopus subject areas

  • Surgery

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