Novel mechanisms of Collagenase Santyl Ointment (CSO) in wound macrophage polarization and resolution of wound inflammation.
Novel mechanisms of Collagenase Santyl Ointment (CSO) in wound macrophage polarization and resolution of wound inflammation.
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胶原酶santyl软膏（CSO）在伤口巨噬细胞极化和伤口炎症的分辨率中的新型机制。
DOI：
10.1038/s41598-018-19879-w
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发表时间：
2018-01-26
影响因子：
4.6
通讯作者：
Roy S
中科院分区：
文献类型：
--
作者：
Das A;Datta S;Roche E;Chaffee S;Jose E;Shi L;Grover K;Khanna S;Sen CK;Roy S
胶原酶可用于酶促伤口清创。梭菌胶原酶，作为胶原酶Santyl软膏（CSO）销售，被FDA批准用于这种用途。基于胶原酶以及胶原降解产物可以调节免疫细胞功能的科学前提，我们试图研究CSO在伤口炎症中的潜在作用。我们测试了这样一个假设，即除了实施清创术之外，CSO还有助于解决持续性伤口炎症。从载有CSO或凡士林的PVA海绵中分离伤口巨噬细胞并植入小鼠中。在急性和糖尿病伤口的巨噬细胞中观察到促修复极化的显著增加和促炎极化的减少。CSO处理组伤口巨噬细胞显示抗炎细胞因子IL-10和TGF-β的产生增加，促炎细胞因子TNF-α和IL-1β的水平降低。CSO的活性成分CS-API离体诱导骨髓/M（IL-4）极化标志物的表达。CS-API处理减弱NF-κB的反式激活并显著诱导STAT 6磷酸化。新的PGE 2-EP 4通路在CS-API诱导的STAT 6活化和骨髓/M（IL-4）极化中的重要作用被鉴定。总之，这项工作的发现将CSO重新定位为可能有效解决伤口炎症（包括糖尿病伤口）的潜在药物。
Collagenases are useful in enzymatic wound debridement. Clostridial collagenase, marketed as Collagenase Santyl Ointment (CSO), is FDA approved for such use. Building on the scientific premise that collagenases as well as collagen degradation products may regulate immune cell function, we sought to investigate the potential role of CSO in wound inflammation. We tested the hypothesis that in addition to enacting debridement, CSO contributes to the resolution of persistent wound inflammation. Wound macrophages were isolated from PVA sponges loaded with CSO or petrolatum and implanted in mice. Significant increase in pro-reparative and decrease in pro-inflammatory polarization was noted in macrophages of acute as well as diabetic wounds. Wound macrophages from CSO-treated group displayed increased production of anti-inflammatory cytokines IL-10 and TGF-β, and decreased levels of pro-inflammatory cytokines TNF-α and IL-1β. The active ingredient of CSO, CS-API, induced the expression of mϕheal /M(IL-4) polarization markers ex vivo. CS-API treatment attenuated transactivation of NF-κB and significantly induced STAT6 phosphorylation. A significant role of a novel PGE2-EP4 pathway in CS-API induced STAT6 activation and the mϕheal /M(IL-4) polarization was identified. Taken together, findings of this work reposition CSO as a potential agent that may be effective in resolving wound inflammation, including diabetic wounds.
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DOI：
10.1111/wrr.12229
发表时间：
2014-11
期刊：
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
影响因子：
--
作者：
Elgharably H;Ganesh K;Dickerson J;Khanna S;Abas M;Ghatak PD;Dixit S;Bergdall V;Roy S;Sen CK
通讯作者：
Sen CK
影响因子：
2.3
作者：
Falanga, V
通讯作者：
Falanga, V
DOI：
10.1073/pnas.93.13.6231
发表时间：
1996-06-25
影响因子：
11.1
作者：
Ghilardi, N;Ziegler, S;Skoda, RC
通讯作者：
Skoda, RC
影响因子：
4.8
作者：
Gordillo, Gayle M.;Biswas, Ayan;Sen, Chandan K.
通讯作者：
Sen, Chandan K.
DOI：
10.4049/jimmunol.1502270
发表时间：
2016-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Das A;Ghatak S;Sinha M;Chaffee S;Ahmed NS;Parinandi NL;Wohleb ES;Sheridan JF;Sen CK;Roy S
通讯作者：
Roy S