Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Korea.
Interdisciplinary Graduate Program for Artificial Intelligence Smart Convergence Technology, Korea University, Sejong 30019, Korea.
Int J Mol Sci. 2021 Apr 28;22(9):4652. doi: 10.3390/ijms22094652.
Microbe-derived factors trigger innate immune responses through the production of inflammatory mediators, including pentraxin 3 (PTX3). PTX3 is a soluble pattern recognition molecule that stimulates the clearance of clinically important bacterial pathogens such as . However, the factors responsible for the production of PTX3 have not been elucidated. In this study, we found that DnaK, a homolog of heat shock protein 70, induced PTX3 production. Induction was mediated by intracellular signals transmitted through the Toll-like receptor 4 (TLR4) signaling pathway. Following receptor engagement, the stimulatory signals were relayed initially through the nuclear factor kappa B (NF-κB) signaling pathway and subsequently by extracellular signal-regulated kinases (ERK), which are mitogen-activated protein kinases. However, ERK activation was negatively controlled by NF-κB, implying the existence of negative crosstalk between the NF-κB and the ERK pathways. These data suggest that DnaK acts as a pathogen-associated molecular pattern to trigger modulation of host defense responses via production of PTX3.
微生物来源的因子通过产生炎症介质触发先天免疫反应，包括五聚素 3（PTX3）。PTX3 是一种可溶性模式识别分子，可刺激清除临床重要的细菌病原体，如 。然而，负责产生 PTX3 的因子尚未阐明。在这项研究中，我们发现 DnaK，热休克蛋白 70 的同源物，诱导 PTX3 的产生。诱导是通过 Toll 样受体 4（TLR4）信号通路传递的细胞内信号介导的。受体结合后，刺激信号首先通过核因子 kappa B（NF-κB）信号通路传递，然后通过细胞外信号调节激酶（ERK）传递，ERK 是丝裂原激活蛋白激酶。然而，ERK 的激活受到 NF-κB 的负调控，这意味着 NF-κB 和 ERK 通路之间存在负交叉对话。这些数据表明， DnaK 作为一种病原体相关分子模式，通过产生 PTX3 来触发宿主防御反应的调节。
