A vitamin D3 analog augmented interleukin-8 production by human monocytic cells in response to various microbe-related synthetic ligands, especially NOD2 agonistic muramyldipeptide
A vitamin D3 analog augmented interleukin-8 production by human monocytic cells in response to various microbe-related synthetic ligands, especially NOD2 agonistic muramyldipeptide
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维生素 D3 类似物可增强人单核细胞响应各种微生物相关合成配体（尤其是 NOD2 激动性胞壁酰二肽）产生的白细胞介素 8
DOI：
10.1016/j.intimp.2012.10.027
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发表时间：
2013
影响因子：
5.6
通讯作者：
H.
中科院分区：
文献类型：
--
作者：
Ikeuchi;T.;Nakamura;T.;Fukumoto;S.;and Takada;H.
活性代谢物维生素D3（1α，25-dihydroxyvitamin D3）是一种多效性因子，具有多种生理功能，包括免疫调节活性。在这项研究中，可能的调节天然免疫反应的人单核细胞的维生素D3类似物进行了检查。用OCT、维生素D3类似物、1α，25-二羟基-22-氧杂维生素D3预处理人单核细胞THP-1细胞，然后用各种化学合成的Toll样受体（TLR）和NOD 1和NOD 2配体刺激。在用各种化学合成的配体刺激时，OCT处理的细胞比未处理的细胞产生更多的IL-8：TLR 2-激动性脂肽（FSL-1）、TLR 3-激动性聚I：C、TLR 4-激动性脂质A（E.大肠杆菌型LA-15-PP）、NOD 1-激动性FK 565和NOD 2-激动性胞壁酰二肽（MDP）。在这些配体中，MDP是OCT处理的THP-1细胞中IL-8产生的最高诱导剂，并且IL-8产生取决于处理时间增加，直到72 h。OCT可上调THP-1细胞NOD 2的表达，MAPK通路中的p38、JNK和ERK、NF-κB通路中的IκBα以及MDP诱导的上游TAK 1的活化程度均高于未处理细胞。使用针对NOD 2的siRNA和特异性信号分子的抑制剂的分析表明，NOD 2的存在和上述信号分子的活化是OCT处理的THP-1细胞中IL-8产生增强所必需的。这些结果表明，NOD 2，NF-κB和MAPK通路参与OCT的活性，以增强人单核细胞对MDP的反应。
Active metabolite vitamin D3, 1α,25-dihydroxyvitamin D3, is a pleiotropic factor and exhibits various physiological functions, including immunomodulating activities. In this study, the possible regulation of innate immune responses of human monocytic cells by a vitamin D3analog was examined. Human monocytic THP-1 cells were pre-treated with OCT, vitamin D3analog, 1α,25-dihydroxy-22-oxavitamin D3, followed by stimulation with various chemically synthesized Toll-like receptors (TLR) and NOD1 and NOD2 ligands. OCT-treated cells produced more IL-8 than non-treated cells upon stimulation with various chemically-synthesized ligands: TLR2-agonistic lipopeptide (FSL-1), TLR3-agonistic poly I:C, TLR4-agonistic lipid A (E. coli-type LA-15-PP), NOD1-agonistic FK565 and NOD2-agonistic muramyldipeptide (MDP). Among the ligands, MDP was the highest inducer of IL-8 production in OCT-treated THP-1 cells, and IL-8 production increased depending on the treatment time until 72h. OCT up-regulated the expression of NOD2 in THP-1 cells, and OCT-treated cells exhibited higher activation of p38, JNK and ERK in the MAPK pathway, IκBα in the NF-κB pathway, and TAK1 upstream in response to MDP than non-treated cells. Analysis using siRNA against NOD2 and inhibitors of specific signal molecules indicated that the existence of NOD2 and activation of the above signaling molecules are required for enhanced production of IL-8 in OCT-treated THP-1 cells. These findings suggested that NOD2, NF-κB and MAPK pathways are involved in the activity of OCT to augment the response of human monocytic cells to MDP.