Wu Xiang-Yu, Nie Li, Lu Xin-Jiang, Fei Chen-Jie, Chen Jiong
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo City, China; Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Meishan Campus, Ningbo University, Ningbo City, China; Collaborative Innovation Center for Zhejiang Marine High-efficiency and Healthy Aquaculture, School of Marine Sciences, Ningbo University, Ningbo City, China.
Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Meishan Campus, Ningbo University, Ningbo City, China; Collaborative Innovation Center for Zhejiang Marine High-efficiency and Healthy Aquaculture, School of Marine Sciences, Ningbo University, Ningbo City, China.
Fish Shellfish Immunol. 2022 Apr;123:50-60. doi: 10.1016/j.fsi.2022.02.021. Epub 2022 Feb 25.
The peroxisome proliferator-activated receptor gamma (PPARγ) are nuclear receptors with distinct roles in energy metabolism and immunity. Although extensively studied in mammals, immunomodulatory roles of this molecule in teleost fish remain to be investigated. In this study, large yellow croaker (Larimichthys crocea) PPARγ (LcPPARγ) sequence was cloned, which encodes a polypeptide of 541 amino acids that include signature domains belonging to the nuclear receptor superfamily. Phylogenetically, LcPPARγ was most closely related to PPARγ derived from European sea bass (Dicentrarchus labrax). Quantitative analysis shown a ubiquitous expression of this molecule, with highest expression level detected in the intestine. The expression of LcPPARγ was decreased in the intestine, muscle, body kidney, spleen and head kidney-derived monocytes/macrophages (MO/MФs) over the course of Vibrio alginolyticus (V. alginolyticus) infection. In contrast, an up-regulation of LcPPARγ was observed in head kidney-derived MO/MФs following docosahexaenoic acid (DHA) treatment. This increase in LcPPARγ leads to an up-regulation of LcCD11b and LcCD18 and an enhancement of complement-mediated phagocytosis. Furthermore, cytokine secretions of V. alginolyticus-stimulated MO/MФs were modulated following LcPPARγ activations that up-regulated the expression of LcIL-10, while decreased the expression of LcIL-1β, LcTNF-α and LcTGF-β1. Overall, our results indicated that LcPPARγ plays a role in regulating functions of MO/MФs and likely contribute to MO/MФs polarization.
过氧化物酶体增殖物激活受体γ(PPARγ)是在能量代谢和免疫中具有不同作用的核受体。尽管在哺乳动物中已进行了广泛研究,但该分子在硬骨鱼中的免疫调节作用仍有待研究。在本研究中,克隆了大黄鱼(Larimichthys crocea)的PPARγ(LcPPARγ)序列,其编码一个由541个氨基酸组成的多肽,该多肽包含属于核受体超家族的特征结构域。在系统发育上,LcPPARγ与源自欧洲海鲈(Dicentrarchus labrax)的PPARγ关系最为密切。定量分析表明该分子普遍表达,在肠道中检测到最高表达水平。在溶藻弧菌(V. alginolyticus)感染过程中,LcPPARγ在肠道、肌肉、体肾、脾脏和头肾来源的单核细胞/巨噬细胞(MO/MФs)中的表达降低。相反,在二十二碳六烯酸(DHA)处理后,头肾来源的MO/MФs中观察到LcPPARγ上调。LcPPARγ的这种增加导致LcCD11b和LcCD18上调以及补体介导的吞噬作用增强。此外,在LcPPARγ激活后,溶藻弧菌刺激的MO/MФs的细胞因子分泌受到调节,LcPPARγ激活上调了LcIL-10的表达,同时降低了LcIL-1β、LcTNF-α和LcTGF-β1的表达。总体而言,我们的结果表明LcPPARγ在调节MO/MФs的功能中起作用,并可能有助于MO/MФs的极化。