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Molecular cloning, expression and biological activity of rhesus macaque interleukin-17A and interleukin-17F
- Cui, Yan-Fang, Yu, Lei, Wang, Feng-Jie, Shen, Xiu-Li, Yang, Gui-Bo
- Molecular immunology 2019 v.114 pp. 196-206
- Macaca mulatta, amino acid sequences, antibacterial proteins, autoimmune diseases, bioactive properties, cysteine, digestive system diseases, exons, glycosylation, human cell lines, humans, inflammation, interleukin-17, interleukin-6, intestines, introns, molecular cloning, occludins, phosphorylation, sequence analysis, tight junctions, tissues, transcription factor NF-kappa B, tumor necrosis factor-alpha
- Interleukin-17A (IL-17A) and interleukin-17F (IL-17F) as two potent proinflammatory cytokines and the signature cytokines of Th17 cells play important roles in human autoimmune diseases, inflammation and host defenses. In this study, rhesus macaque IL-17A (rhIL-17A) and IL-17F (rhIL-17F) were cloned and expressed, and their biological activities and in vivo distribution were examined. The resulting data showed that both the rhIL-17A and rhIL-17F genes were consisted of three exons and two introns. RhIL-17A and rhIL-17F shared 96.8% and 93.9% amino acid sequence identity with human IL-17A (huIL-17A) and IL-17F (huIL-17F) respectively and the sequences also shared one N-glycosylation site and six conserved cysteine residues with huIL-17A and huIL-17F. IL-17A and IL-17F transcripts were highly expressed in lymphoid tissues and the intestinal tract of rhesus macaques. Functionally, recombinant rhIL-17A and rhIL-17F showed similar effect on Act1 levels and NF-κB phosphorylation compared with that of commercial human IL-17A and IL-17F. Moreover, the antibacterial proteins (such as β-defensin 2, S100A8, S100A9, RegIIIα and Muc1) and the tight junction associated genes (including CLDN1, CLDN4, OCLN, and ZO1) expressed by Caco-2 cells were largely enhanced after treatment with rhIL-17A and rhIL-17F. Meanwhile, purified rhIL-17A and rhIL-17F could also induce the expression of IL-6 and TNF-α by THP-1 cells. These data indicated that rhesus macaque IL-17A and IL-17F are highly similar to that of humans in both structure and function. Studies on rhIL-17A/rhIL-17F are promising approach to contribute to the understanding of human IL-17A and IL-17F-related intestinal diseases.