Arginine regulates inflammation response-induced by Fowl Adenovirus serotype 4 via JAK2/STAT3 pathway

Fowl Adenovirus serotype 4 (FAdV-4) infection causes severe inflammatory response leading to hepatitis-hydropericardium syndrome (HHS) in poultry. As an essential functional amino acid of poultry, arginine plays a critical role in anti-inflammatory and anti-oxidative stress.

In this study, the differential expression genes (DEGs) were screened by transcriptomic techniques, and the DEGs in gene networks of inflammatory response-induced by FAdV-4 in broiler's liver were analyzed by Kyoto encyclopedia of genes and genomes (KEGG) enrichment. The results showed that the cytokines pathway and JAK/STAT pathway were significantly enriched, in which the DEGs levels of IL-6, IL-1β, IFN-α, JAK and STAT were significantly up-regulated after FAdV-4 infection. It was further verified with real-time fluorescence quantitative polymerase chain reaction (Real-time qPCR) and Western blotting (WB) in vitro and in vivo. The findings demonstrated that FAdV-4 induced inflammatory response and activated JAK2/STAT3 pathway. Furthermore, we investigated whether arginine could alleviate the liver inflammation induced by FAdV-4. After treatment with 1.92% arginine level diet to broilers or 300 μg/mL arginine culture medium to LMH cell line with FAdV-4 infection at the same time, we found that the mRNA levels of IL-6, IL-1β, IFN-α and the protein levels of p-JAK2, p-STAT3 were down-regulated, compared with FAdV-4 infection group. Furthermore, we confirmed that the inflammation induced by FAdV-4 was ameliorated by pre-treatment with JAK inhibitor AG490 in LMH cells, and it was further alleviated in LMH cells treatment with AG490 and ARG.

These above results provide new insight that arginine protects hepatocytes against inflammation induced by FAdV-4 through JAK2/STAT3 signaling pathway.