RESUMEN
Objective To investigate the possible role of p38 mitogen-activated protein kinase (MAPK) in lung injury following intestinal ischemia reperfusion (II/R) in mice. Methods Intestinal ischemia/reperfusion was induced by occluding the superior mesenteric artery for 45 min followed by 6 h reperfusion. C57BL/6 mice were randomly divided into sham-operated group (sham group), II/R group and II/R plus SB239063 treatment (SB239063 group), n = 6/group. SB239063 (3 mg/kg), a novel second-generation p38 MAPK inhibitor, was administered intraperitoneally one hour before clamping. Pulmonary p38 MAPK and phospho-p38 MAPK protein were measured by Western blotting analysis. Gene expression of TNF-α and IL-1β in the lung was analyzed by RT-PCR. The lung pathology was observed by optical microscope. Results Compared with the sham- operated group, pulmonary p38 MAPK activation was significantly increased 6 h after II/R (P<0. 01), whereas SB239063 could markedly attenuate p38 MAPK activation in lung tissue (P<0. 05). In addition, the increased TNF-α and IL-1β mRNA levels induced by II/R in lungs were significantly blocked by inhibiting p38 MAPK activation (P<0. 05). SB239063 treatment ameliorated the pathologic lung injury induced by II/R. Conclusion p38 MAPK plays an important role in lung injury induced by intestinal ischemia reperfusion (II/R) in mice, and inhibition of p38 MAPK activation prevents lung injury following II/R in mice.
RESUMEN
Th2 cytokines play a pivotal role in the pathogenesis of allergic rhinitis.To investigate the effect of p38 mitogen-activated protein kinase(MAPK)on the production of Th2 cytokines such as IL-4 and IL-5 in allergic rhinitis,a model of allergic rhinitis was established in SD rats.The expression level of p38 MAPK mRNA in PBMCs was detected by means of real time quantitative RT-PCR.The p38 MAPK activity in PBMCs was detected by Western blotting.PBMCs were cultured with various concentrations of p38 MAPK inhibitor SB 239063 or without the treatment,and then IL-4,IL-5 levels of the supernatant were determined by using sandwich ELISA.The results showed that mRNA expression and activity of p38 MAPK in PBMCs were significantly higher in allergic rhinitis rats than in control rats(P<0.05).The p38 MAPK inhibitor SB 239063 decreased the production of IL-4 and IL-5 in a dose-dependent manner.It is concluded that p38 MAPK plays an important role in the pathogenesis of allergic rhinitis which is associated with Th2 cytokines release.