Abstract
BackgroundThe intestinal barrier integrity can be disrupted due to burn injury, which is responsible for local and systemic inflammatory responses. Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage. Interleukin-17A (IL-17A) plays a critical role in inflammatory diseases. However, the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood. In this study, we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury, and furthermore, we sought to determine the early source of IL-17A in the intestine.MethodsMouse burn model was successfully established with infliction of 30% total body surface area scald burn. The histopathological manifestation, intestinal permeability, zonula occludens-1 expression, pro-inflammatory cytokines were determined with or without IL-17A-neutralization. Flow cytometry was used to detect the major source of IL-17A+ cells in the intestine.ResultsBurn caused intestinal barrier damage, increase of intestinal permeability, alteration of zonula occludens-1 expressions, elevation of IL-17A, IL-6, IL-1β and tumor necrosis factor-α (TNF-α), whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption, maintained zonula occludens-1 expression, and noticeably, inhibited pro-inflammatory cytokines elevation. In addition, we observed that the proportion of intestinal IL-17A+Vγ4+ T subtype cells (but not IL-17A+Vγ1+ T subtype cells) were increased in burn group, and neutralization of IL-17A suppressed this increase.ConclusionsThe main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines, and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined. Furthermore, Vγ4+ T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model. These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.
Highlights
The intestinal barrier integrity can be disrupted due to burn injury, which is responsible for local and systemic inflammatory responses
The main original findings of this study are that the intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokine, and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined
We evaluated the levels of IL-17A, IL-6, IL-1β and tumor necrosis factor-α (TNF-α) in each group and found them significantly increased in burn group, but such up-regulation was markedly inhibited via anti-IL-17A antibody treatment, which may be associated with amelioration of burn-induced damage to the intestine barrier, because IL-6, IL-1β directly disrupt intestinal barrier, and promote the induction of naive T lymphocytes towards IL-17A-producing cells to aggravate inflammatory damage to the intestine
Summary
The intestinal barrier integrity can be disrupted due to burn injury, which is responsible for local and systemic inflammatory responses. Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage. Interleukin-17A (IL-17A) plays a critical role in inflammatory diseases. The role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood. We aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury, and we sought to determine the early source of IL-17A in the intestine
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