3,4-Methylenedioxy-β-Nitrostyrene Ameliorates Experimental Burn Wound Progression by Inhibiting the NLRP3 Inflammasome Activation

Prof. Ligen Li1, M.D Meng jing Xiao1

1Burn and Plastic Surgery, First Affiliated Hospital of General Hospital of PLA , Haiding District, Beijing, China

Abstract:

Background: Burn wound progression remains a challenging problem in the clinic. Secondary tissue damage caused by unlimited inflammatory response is considered to be one of the key factors contributing to this clinical problem. Nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome has recently been found to play important roles in immune activation and the inflammatory response after burn/ trauma. This experimental study aims (1) to observe the expression and distribution of NLRP3 inflammasome in burn wounds of a rat burn model and (2) to study whether inhibiting the NLRP3 inflammasome activation would ameliorate burn wound progression.

Methods: A deep second-degree burn was inflicted on the backs of Wistar rats. The expression of NLRP3 inflammasome components and interleukin-1β were determined by Western blot and coimmunoprecipitation. The distribution of NLRP3 inflammasome was assessed by immunohistochemical staining and double-labeling immunofluorescence. Neutrophil infiltration, wound perfusion, burn depth, and wound healing time were assessed. Results: Burn induced remarkable NLRP3 inflammasome activation and cleavage of interleukin-1β. The NLRP3 inflammasome was observed mainly in macrophages of the zone of stasis. 3,4-Methylenedioxy-β-nitrostyrene significantly inhibited NLRP3 inflammasome activation and inflammatory cytokine production in burn wounds. Consequently, neutrophil infiltration was reduced, wound perfusion was restored, burn wound progression was ameliorated, and wound healing was accelerated.

Conclusions: In this study, the authors demonstrated that burn induced NLRP3 inflammasome activation and inflammatory response in wounds, which may be associated with burn wound progression. Treatment with 3,4-methylenedioxy-βnitrostyrene inhibited NLRP3 inflammasome activation, ameliorated burn wound progression, and promoted wound healing.


Biography:

Li Ligen, Professor of Burn and Plastic Surgery , the First Affiliated Hospital of General Hospital of the Chinese People’s Liberation Army, has done some clinical and experimental studies on prevention and treatment to the progressive deepening of deep second degree burn wound .