在慢性退行性炎症疾病中,炎症解消和逐渐抑制期间的热冲击反应
Helena Trevisan Schroeder1, Carlos Henrique De Lemos Muller2, Thiago Gomes Heck3
1Laboratory of Cellular Physiology (FisCel), Department of Physiology, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.
慢性炎症通过破坏热冲击转录因子-1来抑制热冲击反应 (HSR). 了解这种联系是开发炎症疾病新疗法的关键.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
背景情况:
- 热冲击反应 (HSR) 通过热冲击蛋白 (HSPs) 和热冲击转录因子-1 (HSF1) 解决炎症.
- 慢性炎症疾病显示抑制HSR,与西方饮食和久坐的生活方式有关.
- 脂肪组织中的内质网膜应激会启动炎症级联.
研究的目的:
- 研究慢性炎症抑制HSR的机制.
- 探索饮食,生活方式和细胞应激在HSR抑制中的作用.
- 突出HSR评估在炎症疾病中的临床意义.
主要方法:
- 探索将西方饮食,ER压力和炎症联系在一起的分子通路.
- 对未折叠的蛋白质反应和炎症酶激活的分析.
- 通过HuR.研究炎酶激活对HSF1mRNA稳定性的影响.
主要成果:
- 西方饮食和久坐不动的生活方式诱导ER压力,导致蛋白质反应展开和NLRP3炎症酶激活.
- NLRP3炎症酶激活促进与衰老相关的分泌表型和全身炎症.
- NLRP3炎症酶激活降解了HuR,破坏了HSF1mRNA的稳定,并抑制了HSR.
结论:
- 由生活方式因素驱动的慢性炎症,积极抑制HSR.
- 针对HSR抑制机制为炎症性疾病提供了新的治疗途径.
- 可访问的HSR评估对于开发有效的预防和治疗策略至关重要.
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