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NLRP3 inflammasome activity is required for wound healing after burns.

Authors
  • Vinaik, Roohi1
  • Abdullahi, Abdikarim1
  • Barayan, Dalia1
  • Jeschke, Marc G2
  • 1 Sunnybrook Research Institute, Toronto, Canada. , (Canada)
  • 2 Department of Surgery, Division of Plastic Surgery, University of Toronto, Toronto, Canada; Department of Immunology, University of Toronto, Toronto, Canada; Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Sunnybrook Research Institute, Toronto, Canada. Electronic address: [email protected] , (Canada)
Type
Published Article
Journal
Translational research : the journal of laboratory and clinical medicine
Publication Date
Mar 01, 2020
Volume
217
Pages
47–60
Identifiers
DOI: 10.1016/j.trsl.2019.11.002
PMID: 31843468
Source
Medline
Language
English
License
Unknown

Abstract

Survival of burn patients is contingent on effective wound healing, a complex process that requires coordinated responses of myeloid cells and inflammatory pathways. NLRP3, which serves as a platform for secretion of proinflammatory cytokines, is implicated as a central regulator of wound healing. However, its role during the acute dermal and epidermal regeneration in the context of burns is unknown. Wild-type (WT) and NLRP3-/- mice were exposed to a 30% TBSA scald burn. Gene expression was conducted via real-time polymerase chain reaction. Trichrome staining was used to assess collagen deposition and granulation tissue formation. F4/80 immunostaining compared macrophage infiltration. Flow cytometric analysis was used to characterize skin macrophage distribution and profile. NLRP3, IL1β and IL18 expression was upregulated in skin after burn, and these changes were nonexistent in NLRP3-/-. NLRP3-/- had decreased expression of proinflammatory cytokines, chemokines, inflammatory markers, and growth factors at 3 days (P < 0.05). NLRP3-/- burn skin demonstrated significantly less macrophage infiltration and higher expression of anti-inflammatory markers Arg1 and Fizz1 (P < 0.05) compared to WT. Trichrome staining showed decreased collagen deposition compared to WT. We show that NLRP3 is protective in burn wound healing, primarily through production of inflammatory mediators, macrophage recruitment, and polarization to a proinflammatory phenotype. Our findings highlight a central role of NLRP3 in wound healing through regulation of inflammation and macrophage polarization after burns. Copyright © 2019 Elsevier Inc. All rights reserved.

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