Poultry Science (Jan 2024)
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 inhibition alleviates intestinal impairment induced by chronic heat stress in finisher broilers
Abstract
ABSTRACT: Heat stress (HS) in poultry has deleterious effects on intestinal development and barrier function, along with inflammatory outbursts. In the present study, chronic HS reduced body weight of broilers and activated mucosa-associated lymphoid tissue lymphoma translocation protein 1 (Malt1) /nuclear factor kappa B (NF-κB) signaling pathways to elicit the inflammatory cytokine response in jejunum. Subsequently, this study investigated the protective effects of the Malt1 inhibitor on the intestine of broilers under HS conditions. The 21-day-old male broilers were allocated to 8 pens housed in HS room (34°C for 7 h/d) until 28 d of age. During this period, 4 birds were selected from each heat-stressed pen and received intraperitoneal injection of 20 mg/kg body weight Mepazine (a Malt1 inhibitor) or the equivalent volume of phosphate buffer saline (PBS) every other day. When compared to PBS broilers, birds received Mepazine injection exhibited increased relative weight and higher villus height in jejunum (both P < 0.05). Mepazine treatment also increased (P < 0.05) the mRNA of zonula occludens-1 (ZO-1), claudin-1, and cadherin 1 of jejunum, which was companied by the reduced caspase-3 transcription under HS condition. Meanwhile, the gene expression levels of toll-like receptor 4 (TLR4), Malt1, NF-κB, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the jejunum were significantly downregulated by Mepazine administration (P < 0.05). Although there were no significant differences in the relative weight of the thymus and bursa, the transcription levels of T helper 1 (Th1)- and Th17-related cytokines were lower in thymus of birds injected with Mepazine. The cytokines of Treg cytokine transforming growth factor beta (TGF-β) and forkhead box protein P3 (Foxp3) in both the thymus and bursa were not influenced. These results suggest that inhibition of Malt1 protease activity can protect intestinal integrity by promoting the production of tight junction proteins and attenuating NF-κB-mediated intestinal inflammation response under HS conditions.