PMID- 26826426 OWN - NLM STAT- MEDLINE DCOM- 20170106 LR - 20170107 IS - 1879-0089 (Electronic) IS - 0145-305X (Linking) VI - 59 DP - 2016 Jun TI - Grass carp TGF-beta1 impairs IL-1beta signaling in the inflammatory responses: Evidence for the potential of TGF-beta1 to antagonize inflammation in fish. PG - 121-7 LID - S0145-305X(16)30018-0 [pii] LID - 10.1016/j.dci.2016.01.018 [doi] AB - In the present study, effects of TGF-beta1 on IL-1beta signaling during inflammatory response were examined in grass carp. In grass carp head kidney leukocytes (HKLs), LPS significantly induced the mRNA expression of grass carp TGF-beta1 (gcTGF-beta1) and IL-1beta, indicating the involvement of TGF-beta1 and IL-1beta in inflammatory process. Using anti-IL-1beta antibody to neutralize the endogenous IL-1beta, we found that stimulation of IL-1beta mRNA expression by LPS was independent on IL-1beta itself. Interestingly, recombinant gcTGF-beta1 (rgcTGF-beta1) suppressed basal and LPS-stimulated IL-1beta mRNA expression in spite of immunoneutralizing endogenous IL-1beta or not. Given that IL-1beta receptor signaling molecule and natural IL-1beta inhibitors are the important regulators in IL-1beta signaling and activity, the effect of LPS on these molecules' expression was determined in HKLs. Results showed that LPS significantly enhanced the mRNA levels of IL-1 receptor type I (IL-1RI) and II (IL-1RII), IL-1R accessory protein (IL-1Racp) and novel IL-1 family member (nIL-1F). Moreover, the induction of IL-1RII, IL-1Racp and nIL-1F by LPS was IL-1beta-dependent since IL-1beta immunoneutralization abolished these inductions, implying the involvement of IL-1beta auto-induction in these effects. Consistently, TGF-beta1 could block basal IL-1RI and nIL-1F mRNA expression, and LPS-induced IL-1RI, IL-1Racp and nIL-1F mRNA expression, suggesting these molecules as the regulatory sites for TGF-beta1 to modulate IL-1beta signaling. Subsequent in vivo studies showed that bacterial challenge significantly up-regulated IL-1beta mRNA expression with a rapid and transient pattern and TGF-beta1 mRNA expression with a relatively time-delayed kinetics in head kidney. These expression patterns coincide with their pro-inflammatory and anti-inflammatory roles, respectively. As expected, rgcTGF-beta1 could suppress bacterial-induced IL-1beta mRNA expression, strengthening the anti-inflammatory role of TGF-beta1 in vivo. Taken together, these results to our knowledge provide the first evidence for inducible TGF-beta1 expression in inflammatory process, as well as the induction of inflammatory stimuli on IL-1beta expression and signaling. In turn, TGF-beta1 suppressed the proinflammatory process in vitro and in vivo presumably via interfering IL-1beta expression and signaling in inflammatory response, highlighting the potential of TGF-beta1 in the control of inflammation in fish. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. 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. FAU - Yang, Xiao AU - Yang X AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. FAU - Wen, Chao AU - Wen C AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. FAU - Gao, Yajun AU - Gao Y AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. FAU - Qin, Lei AU - Qin L AD - School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. FAU - Zhang, Shengnan AU - Zhang S 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 - Yang, Kun AU - Yang K 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160128 PL - United States TA - Dev Comp Immunol JT - Developmental and comparative immunology JID - 7708205 RN - 0 (Antibodies) RN - 0 (Interleukin-1beta) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Interleukin-1) RN - 0 (Transforming Growth Factor beta1) SB - IM MH - Aeromonas hydrophila/*immunology MH - Animals MH - Antibodies/immunology MH - Carps/*immunology/microbiology MH - Fish Diseases/*immunology/microbiology MH - Gram-Negative Bacterial Infections/*immunology/microbiology MH - Head Kidney/cytology/immunology MH - Inflammation/*immunology MH - Interleukin-1beta/genetics/*immunology MH - Leukocytes/cytology/immunology MH - Lipopolysaccharides/immunology MH - RNA, Messenger/biosynthesis MH - Receptors, Interleukin-1/genetics MH - Signal Transduction/immunology MH - Transforming Growth Factor beta1/genetics/*immunology OTO - NOTNLM OT - Antagonistic effect OT - Grass carp OT - IL-1beta OT - Inflammatory response OT - TGF-beta1 EDAT- 2016/01/31 06:00 MHDA- 2017/01/07 06:00 CRDT- 2016/01/31 06:00 PHST- 2015/11/11 00:00 [received] PHST- 2016/01/25 00:00 [revised] PHST- 2016/01/26 00:00 [accepted] PHST- 2016/01/31 06:00 [entrez] PHST- 2016/01/31 06:00 [pubmed] PHST- 2017/01/07 06:00 [medline] AID - S0145-305X(16)30018-0 [pii] AID - 10.1016/j.dci.2016.01.018 [doi] PST - ppublish SO - Dev Comp Immunol. 2016 Jun;59:121-7. doi: 10.1016/j.dci.2016.01.018. Epub 2016 Jan 28.