TY - JOUR
T1 - Blockade of p38 mitogen-activated protein kinase pathway ameliorates delayed intestinal transit in burned rats
AU - Gan, Hua Tian
AU - Pasricha, Pankaj J.
AU - Chen, Jiande D.Z.
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
KW - Burn
KW - Cyclooxygenase-2 (COX-2)
KW - Intestinal transit
KW - Nitric oxide synthase (iNOS)
KW - p38 MAPK
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U2 - 10.1016/j.amjsurg.2006.05.019
DO - 10.1016/j.amjsurg.2006.05.019
M3 - Article
C2 - 17368305
AN - SCOPUS:33947189117
SN - 0002-9610
VL - 193
SP - 530
EP - 537
JO - American journal of surgery
JF - American journal of surgery
IS - 4
ER -