Li Changzhi, Wang Dong, Guan Xin, Liu Shuang, Su Peng, Li Qingwei, Pang Yue
College of Life Science, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China.
College of Life Science, Liaoning Normal University, Dalian, 116081, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116081, China.
Dev Comp Immunol. 2019 Mar;92:50-59. doi: 10.1016/j.dci.2018.11.008. Epub 2018 Nov 10.
High mobility group box protein 1 (HMGB1) acts as a potent proinflammatory cytokine that involves in the pathogenesis of diverse inflammatory and infectious disorders. In previous study, we identified a homolog of HMGB1 in the Lampetra japonica(L-HMGB1), and further revealed that L-HMGB1 was able to induce the production of tumor necrosis factor-α (TNF-α) in activated human acute monocytic leukemia cells. However, the role of L-HMGB1 played in lamprey was unknown. Here, we found that L-HMGB1 was located in the cytoplasm of lamprey leukocytes and supraneural body (SB) cells. Importantly, we demonstrated that L-HMGB1 participated in activation of various key molecules in inflammation signaling pathway. LPS also promoted the release of L-HMGB1 from SB cells similar to Hu-HMGB1, and then extracellular L-HMGB1 in turn induced the release of cytokines. This study revealed that the synergistic action of LPS and L-HMGB1 played a crucial role in inflammation in lamprey. Our results suggested that lampreys used L-HMGB1 to activate their innate immunity for the purpose of pathogen defense.
高迁移率族蛋白B1(HMGB1)作为一种强效促炎细胞因子,参与多种炎症和感染性疾病的发病机制。在先前的研究中,我们在日本七鳃鳗中鉴定出HMGB1的一个同源物(L-HMGB1),并进一步揭示L-HMGB1能够在活化的人急性单核细胞白血病细胞中诱导肿瘤坏死因子-α(TNF-α)的产生。然而,L-HMGB1在七鳃鳗中所起的作用尚不清楚。在此,我们发现L-HMGB1位于七鳃鳗白细胞和神经上体(SB)细胞的细胞质中。重要的是,我们证明L-HMGB1参与炎症信号通路中各种关键分子的激活。脂多糖(LPS)也类似于人HMGB1(Hu-HMGB1)促进L-HMGB1从SB细胞中释放,然后细胞外L-HMGB1反过来诱导细胞因子的释放。这项研究表明,LPS和L-HMGB1的协同作用在七鳃鳗的炎症中起关键作用。我们的结果表明,七鳃鳗利用L-HMGB1激活其固有免疫以防御病原体。