UQ Diamantina Institute, Translational Research Institute, The University of Queensland, Wooloongabba, QLD 4102, Australia.
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
Int J Mol Sci. 2018 Oct 23;19(11):3289. doi: 10.3390/ijms19113289.
The incidence of chronic wounds is escalating, and the associated healing process is especially problematic in an aging population with increased morbidity. Targeting increased inflammation in chronic wounds is a promising but challenging therapeutic strategy. Indeed, inflammation and especially macrophages are required for wound healing. As the NLRP3 inflammasome has been implicated with various other inflammatory diseases, in this study, we used MCC950-a selective NLRP3 small molecule inhibitor-on murine models of both acute and chronic wounds. This molecule, while tested for other inflammatory conditions, has never been investigated to reduce topical inflammation driving chronic wounds. We found that there were no significant differences when the treatment was applied either topically or orally in wild-type C57Bl/6 mice and that it even impaired wound healing in obese mice. The treatment was also unable to improve re-epithelialisation or angiogenesis, which are both required for the closure of wounds. We are inclined to believe that MCC950 may inhibit the closure of chronic wounds and that it does not alter wound-associated macrophage polarisation.
慢性伤口的发病率正在不断上升，而在发病率增加的老龄化人群中，相关的愈合过程尤其成问题。针对慢性伤口中炎症增加的靶向治疗是一种很有前途但具有挑战性的治疗策略。事实上，炎症，尤其是巨噬细胞，是伤口愈合所必需的。由于 NLRP3 炎性小体与其他各种炎症性疾病有关，在这项研究中，我们使用 MCC950（一种选择性 NLRP3 小分子抑制剂）对急性和慢性伤口的小鼠模型进行了研究。这种药物虽然已经在其他炎症性疾病中进行了测试，但从未被研究用于减轻导致慢性伤口的局部炎症。我们发现，在野生型 C57Bl/6 小鼠中，无论是局部还是口服应用这种药物，都没有显著差异，而且它甚至会损害肥胖小鼠的伤口愈合。该治疗方法也无法改善再上皮化或血管生成，这两者都是伤口闭合所必需的。我们倾向于认为 MCC950 可能会抑制慢性伤口的闭合，并且它不会改变与伤口相关的巨噬细胞极化。
