Characterization of tree shrew (Tupaia belangeri) interleukin-6 and its expression pattern in response to exogenous challenge

Tree shrews, one of the closest relatives of primates, have attracted increasing attention as a model of human diseases, particularly for viral infections. As the first line of defense against microbial pathogens, the innate immune system is crucial in tree shrews. Interleukin-6 (IL-6) is important in the pathophysiology of infection, inflammation and cancer, where it promotes disease development or sustains immune reactions. The present study aimed to obtain further insight into the tree shrew IL-6 (tsIL-6) system, and the function of tsIL-6 in the antiviral and antibacterial response. In the present study, the mRNA and genomic sequence of the tsIL-6 gene were characterized, and the tissue distribution and expression profile of this gene were analyzed in response to lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (poly I:C) treatment. The full-length tsIL-6 mRNA consisted of 1,152 bp with an open reading frame of 627 bp encoding 208 amino acids, a 5'-untranslated region (UTR) of 62 bp, and a 3'-UTR of 436 bp. The genome sequence of the tsIL-6 gene was 5,265 bp in length, comprising of five exons and four introns. The predicted tsIL-6 protein contained a 25-amino-acid-long signal peptide and a conserved IL-6 domain. Phylogenetic analysis based on the coding sequences revealed that tsIL-6 was closely related to IL-6 in humans. Residues crucial for receptor binding were completely conserved in the tree shrew protein. Reverse transcription-polymerase chain reaction analysis revealed that tsIL-6 mRNA was expressed in all examined tissues of healthy tree shrews, with high levels in the muscle and spleen. Following poly I:C challenge, the expression levels of tsIL-6 were upregulated in four tissues associated with immune system, the liver, spleen, kidney and intestine. Taken together, the molecular and bioinformatics analyses based on the IL-6 sequence revealed that the tree shrew has a close phylogenetic association with humans. These results provide insight for future investigations on the structure and function of tsIL-6.