All-trans retinoic acid alleviates transmissible gastroenteritis virus-induced intestinal inflammation and barrier dysfunction in weaned piglets.

Abstract

Background: Transmissible gastroenteritis virus (TGEV) is one of the main pathogens causing severe diarrhea of piglets. The pathogenesis of TGEV is closely related to intestinal inflammation. All-trans retinoic acid (ATRA) is the main active metabolite of vitamin A, which has immunomodulatory and anti-inflammatory properties. However, it is unclear whether ATRA can alleviate TGEV-induced intestinal inflammation and barrier dysfunction in piglets. This study aimed to investigate the effects of ATRA on growth performance, diarrhea, intestinal inflammation and intestinal barrier integrity of TGEV-challenged piglets.

Methods: In a 19-d study, 32 weaned piglets were randomly divided into 4 treatments: Control group (basal diet), TGEV group (basal diet + TGEV challenge), TGEV + ATRA5 group (basal diet + 5 mg/d ATRA + TGEV challenge) and TGEV + ATRA15 group (basal diet + 15 mg/d ATRA + TGEV challenge). On d 14, piglets were orally administered TGEV or the sterile medium.

Results: Feeding piglets with 5 and 15 mg/d ATRA alleviated the growth inhibition and diarrhea induced by TGEV (P < 0.05). Feeding piglets with 5 and 15 mg/d ATRA also inhibited the increase of serum diamine oxidase (DAO) activity and the decrease of occludin and claudin-1 protein levels in jejunal mucosa induced by TGEV, and maintained intestinal barrier integrity (P < 0.05). Meanwhile, 5 mg/d ATRA feeding increased the sucrase activity and the expressions of nutrient transporter related genes (GLUT2 and SLC7A1) in jejunal mucosa of TGEV-challenged piglets (P < 0.05). Furthermore, 5 mg/d ATRA feeding attenuated TGEV-induced intestinal inflammatory response by inhibiting the release of interleukin (IL)-1β, IL-8 and tumor necrosis factor-α (TNF-α), and promoting the secretion of IL-10 and secretory immunoglobulin A (sIgA) (P < 0.05). Feeding 5 mg/d ATRA also down-regulated the expressions of Toll-like receptors and RIG-I like receptors signaling pathway related genes (TLR3, TLR4, RIG-I, MyD88, TRIF and MAVS) and the phosphorylation level of nuclear factor-κB-p65 (NF-κB p65), and up-regulated the inhibitor kappa B alpha (IκBα) protein level in jejunal mucosa of TGEV-challenged piglets (P < 0.05).

Conclusions: ATRA alleviated TGEV-induced intestinal barrier damage by inhibiting inflammatory response, thus improving the growth performance and inhibiting diarrhea of piglets. The mechanism was associated with the inhibition of NF-κB signaling pathway mediated by TLR3, TLR4 and RIG-I.