PMID- 34716580 OWN - NLM STAT- MEDLINE DCOM- 20220121 LR - 20220121 IS - 1095-8649 (Electronic) IS - 0022-1112 (Linking) VI - 100 IP - 1 DP - 2022 Jan TI - Insights into the functional role of grass carp IL-8 in head kidney leukocytes: pro-inflammatory effects and signalling mechanisms. PG - 192-202 LID - 10.1111/jfb.14934 [doi] AB - Interleukin-8 (IL-8) is a critical chemokine regulating immune cells' chemotaxis as well as their physiological or pathological activations. In fish cells, recombinant IL-8 proteins induced transcriptions of pro-inflammatory cytokines. Nonetheless, the exact mechanisms underlying the function of fish IL-8 as a pro-inflammatory cytokine are still unclear. In this paper, the authors first prepared recombinant grass carp IL-8 (rgcIL-8) using an Escherichia coli expression system, and later confirmed rgcIL-8 increased gene expression of il8, il1beta and tumour necrosis factor alpha (tnfalpha) in grass carp head kidney leukocytes (HKLs). Using signalling pathway inhibitors, the authors showed that rgcIL-8 regulated transcriptions of pro-inflammatory cytokines via MAPK and/or NF-kappaB signalling pathways. They cloned gcIL-8-specific receptor CXCR1 and subsequently discovered that gcIL-8 could increase the activity of NF-kappaB and the transcription of IL-1beta via CXCR1. Simultaneously, antibody neutralization assay showed that endogenous IL-8 is partially relevant to the self-regulation of IL-1beta. Moreover, rgcIL-8 led to the expression of inducible nitric oxide synthase gene, causing an accumulation of nitric oxide in the culture medium of HKLs, suggesting the potential of gcIL-8 to mediate inflammatory response. This study not only enriched the function of IL-8 in teleost but also revealed it as a potential target for the inflammatory control in grass carp. CI - (c) 2021 Fisheries Society of the British Isles. FAU - Zhao, Minghui AU - Zhao M AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China. FAU - Liu, Yazhen AU - Liu Y AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China. FAU - Gao, Yajun AU - Gao Y AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China. FAU - Wang, Xinyan AU - Wang X AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China. FAU - Zhou, Hong AU - Zhou H AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China. FAU - Zhang, Anying AU - Zhang A AUID- ORCID: 0000-0001-7318-5606 AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China. LA - eng GR - 2021YJ0277/applied basic research foundation of sichuan province/ PT - Journal Article DEP - 20211116 PL - England TA - J Fish Biol JT - Journal of fish biology JID - 0214055 RN - 0 (Fish Proteins) RN - 0 (Interleukin-8) SB - IM MH - Animals MH - *Carps/genetics MH - *Fish Diseases MH - Fish Proteins MH - Head Kidney MH - Interleukin-8/genetics MH - Leukocytes MH - Signal Transduction OTO - NOTNLM OT - CXCR1 OT - MAPK OT - NF-kappaB OT - interleukin-8 OT - nitric oxide product EDAT- 2021/10/31 06:00 MHDA- 2022/01/22 06:00 CRDT- 2021/10/30 06:08 PHST- 2021/10/23 00:00 [revised] PHST- 2021/07/28 00:00 [received] PHST- 2021/10/26 00:00 [accepted] PHST- 2021/10/31 06:00 [pubmed] PHST- 2022/01/22 06:00 [medline] PHST- 2021/10/30 06:08 [entrez] AID - 10.1111/jfb.14934 [doi] PST - ppublish SO - J Fish Biol. 2022 Jan;100(1):192-202. doi: 10.1111/jfb.14934. Epub 2021 Nov 16.