HSP72 is a stimulus for activating toll-like receptor 2 in M2 macrophages leading to IL-6-mediated tumor malignancy

IF 1.1 4区 医学 Q4 TOXICOLOGY
Wol Soon Jo, Min Ho Jeong, Soo Kyung Jeong, Su Jung Oh, Ji Sue Baik, Ji An Seo, Jeong-Hwa Baek, Chang Geun Lee, Joong Sun Kim, Sung Dae Kim, Moon-Taek Park
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引用次数: 0

Abstract

Background

M2-polarized macrophages aggressively modulate the tumor microenvironment and enhance tumor cell malignancy. As intracellular molecules are released by damaged or stressed cells, damage-associated molecular patterns (DAMPs) bind to toll-like receptors (TLRs) on cells in the tumor microenvironment, inducing inflammation and epithelial-mesenchymal transition. However, recent studies on the crosstalk between DAMPs and M2-polarized macrophages (M2 macrophages) during tumor progression have not provided conclusive results.

Objective

We investigated the role of toll-like receptors (TLRs) in IL-6 production by M2 macrophages and searched for cancer cell-derived DAMPs that can activate the TLRs responsible for IL-6 production.

Results

TLR2 activation was required for IL-6 production by M2 macrophages. The malignancy of cancer cells was increased by the activation of this pathway. Cancer-derived HSP 72 acted as a ligand that stimulates the TLR2 signaling pathway in M2 macrophages, triggering IL-6 production.

Conclusion

TLR 2 stimulation in M2 macrophages enhances tumor malignancy by upregulating IL-6. Heat shock protein 72 (HSP72) is a potent TLR2 stimulator. Our findings reveal a connection between TLR2 and M2-polarized macrophages in tumor malignancy and may be useful for developing effective treatments for tumor relapse.

Abstract Image

HSP72 是激活 M2 巨噬细胞中收费样受体 2 的刺激物,可导致 IL-6 介导的肿瘤恶变
背景M2极化的巨噬细胞会积极调节肿瘤微环境并增强肿瘤细胞的恶性程度。由于受损或受压细胞释放的细胞内分子,损伤相关分子模式(DAMPs)与肿瘤微环境中细胞上的收费样受体(TLRs)结合,诱发炎症和上皮-间质转化。目的 我们研究了类收费受体(TLRs)在 M2 巨噬细胞产生 IL-6 过程中的作用,并寻找能激活 TLRs 导致 IL-6 产生的癌细胞衍生 DAMPs。这一途径的激活增加了癌细胞的恶性程度。癌症衍生的 HSP 72 可作为配体刺激 M2 巨噬细胞中的 TLR2 信号通路,引发 IL-6 的产生。热休克蛋白 72(HSP72)是一种强效的 TLR2 刺激物。我们的研究结果揭示了 TLR2 与肿瘤恶性肿瘤中 M2 极化巨噬细胞之间的联系,可能有助于开发治疗肿瘤复发的有效方法。
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来源期刊
CiteScore
2.50
自引率
17.60%
发文量
114
审稿时长
6-12 weeks
期刊介绍: Molecular & Cellular Toxicology publishes original research and reviews in all areas of the complex interaction between the cell´s genome (the sum of all genes within the chromosome), chemicals in the environment, and disease. Acceptable manuscripts are the ones that deal with some topics of environmental contaminants, including those that lie in the domains of analytical chemistry, biochemistry, pharmacology and toxicology with the aspects of molecular and cellular levels. Emphasis will be placed on toxic effects observed at relevant genomics and proteomics, which have direct impact on drug development, environment health, food safety, preventive medicine, and forensic medicine. The journal is committed to rapid peer review to ensure the publication of highest quality original research and timely news and review articles.
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