Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No.100, Tzyou 1st Road, Sanmin District, Kaohsiung City, 807, Taiwan, Republic of China.
Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No.100, Tzyou 1st Road, Sanmin District, Kaohsiung City, 807, Taiwan, Republic of China.
Hormones (Athens). 2019 Jun;18(2):179-187. doi: 10.1007/s42000-019-00101-z. Epub 2019 Mar 2.
Chronic inflammation induced by proinflammatory cytokines and chemokines is postulated to be involved in insulin resistance and β-cell dysfunction in type 2 diabetes mellitus (T2DM). Acarbose, the α-glucosidase inhibitor, is an oral antidiabetic drug for T2DM. Acarbose suppresses inflammatory cytokine production in patients with T2DM, though the underlying mechanisms are unclear. In the present study, we aimed to investigate the anti-inflammatory effects and the exact mechanisms of acarbose in human monocytic THP-1 cells.
THP-1 cells were pretreated with acarbose and then stimulated with lipopolysaccharide (LPS). The levels of Th1-related chemokines, including interferon-γ-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), Th2-related chemokine macrophage-derived chemokine (MDC), and proinflammatory cytokine tumor necrosis factor-α (TNF-α), were determined by enzyme-linked immunosorbent assay. Intracellular signaling pathways were explored by Western blot analysis and using a chromatin immunoprecipitation assay.
Acarbose suppressed the levels of IP-10, MCP-1, MDC, and TNF-α and downregulated phosphorylation of p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B-p65 (NF-κB-p65) in LPS-stimulated THP-1 cells. Acarbose suppressed LPS-induced acetylation of histones H3 (H3) and H4 in the IP-10 and MCP-1 promoter regions. These findings revealed the suppressive effects of acarbose on IP-10, MCP-1, MDC, and TNF-α production in THP-1 cells via, at least partially, the p38, JNK, ERK, and NF-κB-p65 pathways, as well as through epigenetic regulation via histone H3 and H4 acetylation.
Our study points to the therapeutic anti-inflammatory potential of acarbose.
促炎细胞因子和趋化因子引起的慢性炎症被认为与 2 型糖尿病（T2DM）中的胰岛素抵抗和β细胞功能障碍有关。阿卡波糖是一种用于治疗 T2DM 的α-葡萄糖苷酶抑制剂。阿卡波糖可抑制 T2DM 患者的炎症细胞因子产生，但潜在机制尚不清楚。在本研究中，我们旨在研究阿卡波糖在人单核细胞 THP-1 细胞中的抗炎作用和确切机制。
THP-1 细胞用阿卡波糖预处理，然后用脂多糖（LPS）刺激。通过酶联免疫吸附试验测定 Th1 相关趋化因子，包括干扰素-γ诱导蛋白-10（IP-10）、单核细胞趋化蛋白-1（MCP-1）、Th2 相关趋化因子巨噬细胞衍生趋化因子（MDC）和促炎细胞因子肿瘤坏死因子-α（TNF-α）的水平。通过 Western blot 分析和染色质免疫沉淀试验探讨细胞内信号通路。
阿卡波糖抑制 LPS 刺激的 THP-1 细胞中 IP-10、MCP-1、MDC 和 TNF-α的水平，并下调磷酸化 p38、c-Jun N-末端激酶（JNK）、细胞外信号调节激酶（ERK）和核因子-κB-p65（NF-κB-p65）。阿卡波糖抑制 LPS 诱导的 IP-10 和 MCP-1 启动子区域组蛋白 H3（H3）和 H4 的乙酰化。这些发现表明，阿卡波糖通过至少部分 p38、JNK、ERK 和 NF-κB-p65 途径以及通过组蛋白 H3 和 H4 乙酰化的表观遗传调节，抑制 THP-1 细胞中 IP-10、MCP-1、MDC 和 TNF-α的产生。
我们的研究表明阿卡波糖具有治疗炎症的潜力。
