原创力文档tgf-β1 exerts opposing effects on grass carp leukocytes implication in teleost immunity, receptor signaling and potential self-regulatory mechanismstgf-β1产生相反的影响草鱼白细胞含义在硬骨鱼类的免疫受体信号和潜在的自律机制.pdfVIP
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tgf-β1 exerts opposing effects on grass carp leukocytes implication in teleost immunity, receptor signaling and potential self-regulatory mechanismstgf-β1产生相反的影响草鱼白细胞含义在硬骨鱼类的免疫受体信号和潜在的自律机制
TGF-b1 Exerts Opposing Effects on Grass Carp
Leukocytes: Implication in Teleost Immunity, Receptor
Signaling and Potential Self-Regulatory Mechanisms
Mu Yang, Xinyan Wang, Danyan Chen, Yanan Wang, Anying Zhang, Hong Zhou*
School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
Abstract
In fish immunity, the regulatory role of transforming growth factor-b1 (TGF-b1) has not been fully characterized. Here we
examined the immunoregulatory effects of TGF-b1 in grass carp peripheral blood leukocytes (PBL) and head kidney
leukocytes (HKL). It is interesting that TGF-b1 consistently stimulated the cell viability and the mRNA levels of pro-
inflammatory cytokines (Tnfa and Ifnc) and T/B cell markers [Cd4-like (Cd4l), Cd8a, Cd8b and Igm] in PBL, which contrasted
with its inhibitory tone in HKL. Further studies showed that grass carp TGF-b1 type I receptor, activin receptor-like kinase 5
(ALK5), was indispensable for the immunoregulatory effects of TGF-b1 in PBL and HKL. Notably, TGF-b1 persistently
attenuated ALK5 expression, whereas immunoneutralization of endogenous grass carp TGF-b1 could increase ALK5 mRNA
and protein levels. It is consistent with the observation that TGF-b1 decreased the number of ALK5+ leukocytes in PBL and
HKL, revealing a negative regulation of TGF-b1 signaling at the receptor level. Moreover, transient treatment with TGF-b1 for
24 h was sufficient to induce similar cellular responses compared with the continuous treatment. This indicated a possible
mechanism by which TGF-b1 triggered the down-regulation of ALK5 mRNA and protein, leading to the desensitization of
grass carp leukocytes toward TGF-b1. Accordingly, our data revealed a dual role of TGF-b1 in teleost immunity in which it
can serve as a positive or negative control
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