Inflammation is a complex biological process which alters the normal physiological function of the immune system resulting in an abnormal microenvironment that leads to several clinical complications. The process of inflammation is mediated through various intracellular signaling factors inside the cells. Apoptosis signal–regulating kinase 1 (ASK1) is an inflammation-derived kinase that controls the activation of other family of kinases such as p38 mitogen–activated protein kinases (p38 MAPKs), which mediates various the inflammatory processes. In this study, we cultured THP-1 macrophage cells to undergo inflammatory proliferation with LPS (1 μg/ml) and TNFα (10 ng/ml) stimulation. Initial in silico analysis was utilized to predict novel microRNAs (miRNAs) that target ASK1 signaling and its expression levels in LPS and TNFα stimulated THP-1 cells were estimated. Among the miRNAs, miR-532-3p showcased the highest binding affinity towards ASK1 kinase. We witnessed that transient transfection of miR-532-3p diminished the levels of ASK1 and downstream phosphorylation/translocation of p38 MAPK. Furthermore, direct targeting of ASK1 resulted in regulation of uncontrolled release of cytokines (TNFα, IL-6, and IL-23) and chemokines (GM-CSF and MIP-2α). Overall, we suggest that miR-532-3p attenuates the pro-inflammatory nature of macrophages by targeting ASK1/p38 MAPK signaling pathway and can be used as a molecular intervention for treating inflammatory diseases.

炎症是一个复杂的生物过程，它会改变免疫系统的正常生理功能，导致微环境异常，从而导致多种临床并发症。炎症过程是通过细胞内的各种细胞内信号因子介导的。细胞凋亡信号调节激酶 1 (ASK1) 是一种炎症衍生激酶，可控制其他激酶家族的激活，如 p38 丝裂原活化蛋白激酶 (p38 MAPK)，后者介导各种炎症过程。在本研究中，我们培养了 THP-1 巨噬细胞，使其在 LPS（1 μg/ml）和 TNFα（10 ng/ml）刺激下进行炎症增殖。初始计算机分析用于预测靶向 ASK1 信号的新型 microRNA (miRNA)，并估计其在 LPS 和 TNFα 刺激的 THP-1 细胞中的表达水平。在 miRNA 中，miR-532-3p 对 ASK1 激酶的结合亲和力最高。我们目睹了 miR-532-3p 的瞬时转染降低了 ASK1 的水平和 p38 MAPK 的下游磷酸化/易位。此外，直接靶向 ASK1 导致调节细胞因子（TNFα、IL-6 和 IL-23）和趋化因子（GM-CSF 和 MIP-2α）的不受控制的释放。总体而言，我们建议 miR-532-3p 通过靶向 ASK1/p38 MAPK 信号通路减弱巨噬细胞的促炎性质，并可用作治疗炎症性疾病的分子干预。