Hua Tian Gan1, Pankaj J Pasricha, Jiande D Z Chen. 1. Department of Geriatrics Medicine, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041, China.
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)-1beta, 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-1beta 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-1beta protein or gene expression increased markedly after burn injury. SB203580 inhibited p38 MAPK and MPO activity, and reduced iNOS, COX-2, and IL-1beta 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-1beta expression. Thus, p38 MAPK could represent a novel target for therapy of gut dysmotility after burn injury.
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)-1beta, 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-1beta 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-1beta protein or gene expression increased markedly after burn injury. SB203580 inhibited p38 MAPK and MPO activity, and reduced iNOS, COX-2, and IL-1beta 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-1beta expression. Thus, p38 MAPK could represent a novel target for therapy of gut dysmotility after burn injury.