丙酮酸脱氢酶复合体E2亚基通过活化Toll样受体4影响单核细胞分泌细胞因子

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Abstract Objective: To explore whether pyruvate dehydrogenase complex E2 subunit (PDC-E2) may activate Toll-like receptor 4 (TLR4)-NF-κB pathway and induce secretion of tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12) and TNF-related apoptosis-inducing ligand (sTRAIL). Methods: PDC-E2 was used to stimulate monocyte line U937, combined with HTA125 (an inhibitory antibody of TLR4) and PDTC (an inhibitor of NF-κB). The study groups included control group, PDC-E2 group, PDC-E2+HTA125 group and PDC-E2+PDTC group. TLR4 on U937 was detected by flow cytometry, activity of NF-κB was determined by EMSA, TNF-α, IL-12 and sTRAIL were measured by ELISA. Results: At 24 h after stimulation by 2, 10 and 50 μg/mL of PDC-E2, TLR4 expression on U937 cell was significantly increased. At 1 h after stimulation by 50 μg/mL of PDC-E2, NF-κB was markedly activated, while at 2 h, the activation of NF-κB was gradually decreased and at 4 h, the decrease was very significant. NF-κB activity was significantly decreased after HTA125 addition compared with that before. At 24 h after stimulation by 50 μg/mL of PDC-E2, supernant TNF-α and sTRAIL levels were significantly higher than that of control, while IL-12 level was of no significant difference. At 24 h and 48 h, the levels of TNF-α, IL-12 and sTRAIL were all significantly higher than that of control. The three cytokines were significantly lower after addition of HTA125 or PDTC than before. Conclusion: PDC-E2 can activate TLR4-NF-κB pathway, by which PDC-E2 stimulates the secretion of TNF-α, IL-12 and sTRAIL by monocyte.

Key words： pyruvate dehydrogenase complex Toll-like receptor 4 nuclear factor cytokine primary biliary cholangitis

Received: 23 November 2016

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	YANG Zaixing
	LIANG Yan
	LIU Donghong
	ZHANG Zhiyu
	ZHONG Renqian.

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2017/V47/I9/637

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