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Functional analyses of the interaction of chicken interleukin 23 subunit p19 with IL-12 subunit p40 to form the IL-23 complex

Author:
Truong, Anh Duc, Hoang, Cong Thanh, Hong, Yeojin, Lee, Janggeun, Lee, Kyungbaek, Lillehoj, Hyun S., Hong, Yeong Ho
Source:
Molecular Immunology 2017
ISSN:
0161-5890
Subject:
chickens, immunity, immunopathology, messenger RNA, transcription factor NF-kappa B, humans, Salmonella, bioinformatics, inflammation, signal transduction, amino acid sequences, mice, amino acids, interleukin-23, GATA transcription factors, receptors, exons, introns, interleukin-12
Abstract:
This study represents the first description of the cloning of chicken IL-23p19 (ChIL-23α) and the function of the IL-23 complex in birds. Multiple alignment of ChIL-23α with other known IL-23α amino acid sequences revealed regions of amino acid conservation. The homologies of ChIL-23α, IL-12p35, and similar mammalian subunits ranged between 26% and 42%. ChIL-23α consisted of four exons and three introns; similar to those in humans and mice, and limited conservation of synteny between the human and chicken genomes was observed. Using bioinformatics tools, we identified the NF-κB, C/EBPα-β, c-Jun, c-Rel, AP-1, GATA-1, and ER promoter sites in ChIL-23α. Moreover, IL-23α mRNA was more highly expressed than IL-12p40 and IL-12p35 mRNA in several organs of chickens infected with Salmonella. In addition, ChIL-23 complex are associated with IL-23R, IL-12Rβ1 receptors; activate the JAK2/TYK2, STAT1/3, SOCS1 genes, and induced proinflammatory cytokines in immune cells. Collectively, these results indicate that ChIL-23 is a member of the IL-12 family, has proinflammatory properties related to IL-23R and IL-12Rβ1 receptor expression, and activates the JAK/STAT signaling pathway that results in the interaction of ChIL-23α with ChIL-12p40 to form the novel ChIL-23 complex. Our results provide novel insights into the regulation of immunity, inflammation, and immunopathology.
Agid:
5837972
Handle:
10113/5837972