title: Grass carp TGF-β1 impairs IL-1β signaling in the inflammatory responses: Evidence for the potential of TGF-β1 to antagonize inflammation in fish.
abstract: In the present study, effects of TGF-β1 on IL-1β 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-β1 (gcTGF-β1) and IL-1β, indicating the involvement of TGF-β1 and IL-1β in inflammatory process. Using anti-IL-1β antibody to neutralize the endogenous IL-1β, we found that stimulation of IL-1β mRNA expression by LPS was independent on IL-1β itself. Interestingly, recombinant gcTGF-β1 (rgcTGF-β1) suppressed basal and LPS-stimulated IL-1β mRNA expression in spite of immunoneutralizing endogenous IL-1β or not. Given that IL-1β receptor signaling molecule and natural IL-1β inhibitors are the important regulators in IL-1β 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-1β-dependent since IL-1β immunoneutralization abolished these inductions, implying the involvement of IL-1β auto-induction in these effects. Consistently, TGF-β1 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-β1 to modulate IL-1β signaling. Subsequent in vivo studies showed that bacterial challenge significantly up-regulated IL-1β mRNA expression with a rapid and transient pattern and TGF-β1 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-β1 could suppress bacterial-induced IL-1β mRNA expression, strengthening the anti-inflammatory role of TGF-β1 in vivo. Taken together, these results to our knowledge provide the first evidence for inducible TGF-β1 expression in inflammatory process, as well as the induction of inflammatory stimuli on IL-1β expression and signaling. In turn, TGF-β1 suppressed the proinflammatory process in vitro and in vivo presumably via interfering IL-1β expression and signaling in inflammatory response, highlighting the potential of TGF-β1 in the control of inflammation in fish.
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wen
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qin
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
authors.forename: Anying
authors.initials: A
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
mesh_terms: D016980:Aeromonas hydrophila / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002347:Carps / Q000276:immunology* / Q000382:microbiology; D005393:Fish Diseases / Q000276:immunology* / Q000382:microbiology; D016905:Gram-Negative Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D060226:Head Kidney / Q000166:cytology / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D017472:Receptors, Interleukin-1 / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology*
chemical_list: D000906:Antibodies; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D053773:Transforming Growth Factor beta1
keywords: Antagonistic effect; Grass carp; IL-1β; Inflammatory response; TGF-β1