Topical p38 MAPK inhibition reduces bacterial growth in an in vivo burn wound model
Topical p38 MAPK inhibition reduces bacterial growth in an in vivo burn wound model
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DOI：
10.1016/j.surg.2007.02.007
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发表时间：
2007-07-01
期刊：
影响因子：
3.8
通讯作者：
Arbabi, Saman
中科院分区：
文献类型：
--
作者：
Ipaktchi, Kyros;Mattar, Aladdein;Arbabi, Saman
背景虽然炎症反应是伤口愈合的先决条件，但先天免疫系统的过度激活可诱导上皮细胞损伤和凋亡，这可能进一步损害真皮完整性。在非感染性烧伤创面模型中，我们先前证明局部抑制p38 MAPK（一种重要的炎症信号通路）可减轻上皮细胞损伤和凋亡。我们现在质疑是否减弱局部炎症会削弱细菌的伤口抵抗力和损害宿主的防御。大鼠接受30%的总体表面积烧伤，并用局部应用p38 MAPK抑制剂或载体处理伤口。伤后24小时，用铜绿假单胞菌接种烧伤创面。伤后48 h处死动物，观察创面愈合情况。接种烧伤伤口诱导显著的细菌生长。接种动物的皮肤炎性变化明显加重。局部p38 A，MAPK抑制减少了烧伤创面中促炎细胞因子的表达和中性粒细胞隔离，有或没有细菌接种。有趣的是，在用局部p38 MAPK介导剂治疗的动物中，细菌伤口生长显著减弱。局部p38 MAPK抑制减弱伤口炎症而不干扰细菌宿主防御。减弱过度的烧伤创面炎症信号可以防止真皮屏障的二次损伤，并减少机会致病菌的生长。
Background. Although the inflammatory response is a prerequisite for wound healing, excessive activation of the innate immune system can induce epithelial cell damage and apoptosis, which may further compromise dermal integrity. In a noninfectious burn wound model, we previously demonstrated that topical inhibition of p38 MAPK, an important inflammatory signaling pathway, attenuated epithelial cell damage and apoptosis. We now question whether attenuating local inflammation would weaken bacterial wound resistance and compromise host defense.Methods. Rats received 30% total body surface area burn, and the wound was treated with topical application of a p38 MAPK inhibitor or vehicle. At 24 hours after injury, burn wounds were inoculated with Pseudomonas aeruginosa. At 48 hours postinjury, animals were sacrificed, and the burn wound was analyzed.Results. Inoculating burn wounds induced significant bacterial growth. Dermal inflammatory changes were markedly accentuated in the inoculated animals. Topical p38 A,MAPK inhibition reduced the proinflammatory cytokine expression in the burn wounds and neutrophil sequestration with or without bacterial inoculation. Interestingly, the bacterial wound growth was significantly attenuated in animals treated with topical p38 MAPK inhibitor.Conclusions. Topical p38 MAPK inhibition attenuated wound inflammation without interfering with bacterial host defense. Attenuation of excessive burn wound inflammatory signaling may prevent secondary damage of the dermal barrier and reduce the growth of opportunistic pathogens.