Novel mechanisms of Collagenase Santyl Ointment (CSO) in wound macrophage polarization and resolution of wound inflammation
| Autor: | Scott Chaffee, Amitava Das, Soma Datta, Lei Shi, Sashwati Roy, Eric Roche, Komel Grover, Elizabeth Jose, Savita Khanna, Chandan K. Sen |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Macrophage polarization lcsh:Medicine Pharmacology Article Ointments 03 medical and health sciences Transactivation Mice medicine Animals lcsh:Science STAT6 chemistry.chemical_classification Inflammation Multidisciplinary integumentary system business.industry Gene Expression Profiling Macrophages lcsh:R 3. Good health 030104 developmental biology Enzyme Microbial Collagenase Treatment Outcome chemistry Collagenase Phosphorylation Cytokines Wounds and Injuries Tumor necrosis factor alpha lcsh:Q business Ex vivo medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|