Gut Liver.  2021 Sep;15(5):771-781. 10.5009/gnl20210.

Interleukin-22 Attenuates Acute Pancreatitis-Associated Intestinal Mucosa Injury in Mice via STAT3 Activation

• Bai J
• Bai J
• Yang M

• KMID: 2520129
• DOI: http://doi.org/10.5009/gnl20210

Abstract

Background/Aims
Interleukin-22 (IL-22) is an important cytokine maintaining homeostasis at barrier surfaces. In this study, the role of IL-22 in acute pancreatitis-associated intestinal injury was further explored.
Methods
Severe acute pancreatitis (SAP) was induced by administration of L-arginine in Balb/c mice at different time gradients. Histopathological examinations were made in both the pancreas and small intestine. Furthermore, recombinant murine IL-22 (rIL-22) was administrated to L-arginine-induced SAP mice by intraperitoneal injection. The mRNA levels of IL-22R1, Reg-IIIβ,Reg-IIIγ, Bcl-2, and Bcl-xL were detected in the small intestine by real-time polymerase chain reaction, and protein levels of total and phosphorylated STAT3 were assessed via Western blot.
Results
Compared with normal control group, 72 hours of L-arginine exposure induced the most characteristic histopathological changes of SAP, evidenced by pathological changes and serum amylase levels. Meanwhile, significant pancreatitis-associated intestinal mucosa injury was also observed. The gene expression levels of antimicrobial proteins Reg-IIIβ, Reg-IIIγ and anti-apoptosis proteins Bcl-2, Bcl-xL were downregulated in small intestine. Furthermore, Larginine-induced SAP was attenuated by rIL-22 treatment. Importantly, pancreatitis-associated intestinal mucosa injury was also ameliorated, reflected by improved pathological changes and significant increase in gene expression levels of Reg-IIIβ, Reg-IIIγ, Bcl-2 and Bcl-xL. Consistently, serum amylase levels and mortality were decreased in mice treated with rIL-22. Mechanistically, the upregulated expressions of these protective genes were achieved by activating STAT3.
Conclusions
Exogenous rIL-22 attenuates L-arginine-induced acute pancreatitis and intestinal mucosa injury in mice, via activating STAT3 signaling pathway and enhancing the expression of antimicrobial peptides and antiapoptotic genes.

Keyword

Interleukin-22; Pancreatitis; Intestinal mucosa; STAT3