PMID- 31734285 OWN - NLM STAT- MEDLINE DCOM- 20201116 LR - 20201116 IS - 1095-9947 (Electronic) IS - 1050-4648 (Linking) VI - 98 DP - 2020 Mar TI - Novel functions of grass carp three p40 isoforms as modulators of Th17 signature cytokine expression in head kidney leukocytes. PG - 995-1000 LID - S1050-4648(19)31068-X [pii] LID - 10.1016/j.fsi.2019.11.025 [doi] AB - Interleukin (IL)-12p40, a component of IL-12 and IL-23, can be secreted as monomer and homodimer in mammals. Our previous study has proved the existence of natural three p40 isoforms and their proinflammatory properties in grass carp. In the present study, we unexpectedly found that recombinant grass carp p40a/b/c (rgcp40a, rgcp40b and rgcp40c) were able to enhance the mRNA levels of grass carp il-17a/f1 (gcil-17a/f1) in a dose- and time-dependent manner in head kidney leukocytes (HKLs). In agreement with these findings, the enzyme-linked immunosorbent assay (ELISA) showed that rgcp40a, rgcp40b and rgcp40c markedly stimulated gcIl-17a/f1 secretion from the HKLs. Together with their stimulatory effects on grass carp gcil-22 and gcil-26 expression, our data suggested their potential to mediate Th17-like response in grass carp. To support this notion, we investigated the underlying mechanisms for the regulation of rgcp40 isoforms on gcil-17a/f1 expression, and found that three rgcp40 isoforms significantly induced the activation of Erk, Jnk and Stat3 pathways in a time-dependent oscillation in the same cell model. Moreover, three rgcp40 isoforms-induced gcil-17a/f1 mRNA expression was suppressed by the inhibition on Erk, Jnk and Stat3 pathways, suggesting the signaling pathways in the p40 isoforms-mediating il-17a/f1 transcription. These studies for the first time proved the involvement of three gcp40 isoforms in mediating Th17 signature cytokine expression in fish immune cells, therefore providing new insights into the roles of p40 in teleost immunity. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Feng, Shiyu AU - Feng S AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. FAU - Zhou, Hong AU - Zhou H AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. Electronic address: zhouhongzh@uestc.edu.cn. FAU - Wang, Yanyan AU - Wang Y AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. FAU - Qiu, Xingyang AU - Qiu X AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. FAU - Zhang, Anying AU - Zhang A AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. FAU - Wang, Xinyan AU - Wang X AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. LA - eng PT - Journal Article DEP - 20191114 PL - England TA - Fish Shellfish Immunol JT - Fish & shellfish immunology JID - 9505220 RN - 0 (Cytokines) RN - 0 (Fish Proteins) SB - IM MH - Animals MH - Carps/*genetics/immunology MH - Cytokines/*genetics/immunology MH - Fish Proteins/*genetics/immunology MH - Gene Expression/*immunology MH - Head Kidney/*immunology MH - Leukocytes/*immunology MH - Th17 Cells/immunology OTO - NOTNLM OT - Grass carp OT - IL12/IL23p40 subunit OT - Il-17a/f1 OT - Isoforms OT - Signaling pathway OT - Th17-like response EDAT- 2019/11/18 06:00 MHDA- 2020/11/18 06:00 CRDT- 2019/11/18 06:00 PHST- 2019/06/24 00:00 [received] PHST- 2019/11/07 00:00 [revised] PHST- 2019/11/13 00:00 [accepted] PHST- 2019/11/18 06:00 [pubmed] PHST- 2020/11/18 06:00 [medline] PHST- 2019/11/18 06:00 [entrez] AID - S1050-4648(19)31068-X [pii] AID - 10.1016/j.fsi.2019.11.025 [doi] PST - ppublish SO - Fish Shellfish Immunol. 2020 Mar;98:995-1000. doi: 10.1016/j.fsi.2019.11.025. Epub 2019 Nov 14.