11β-Hydroxysteroid dehydrogenase type 1 amplifies inflammation in LPS-induced THP-1 cells | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 15، دوره 26، شماره 3، خرداد 2023، صفحه 374-379 اصل مقاله (722.49 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2023.67927.14852 | ||
| نویسندگان | ||
| Lingli Luo؛ Dongmei Zhu؛ Zheng Zhang؛ Hanjie Zeng؛ Min Huang* ؛ Suming Zhou* | ||
| Department of Geriatrics Intensive Care Unit, The First Affiliated Hospital of Nanjing Medical University. NO.300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China | ||
| چکیده | ||
| Objective(s): The role of glucocorticoids as anti-inflammatory and immune-stimulatory drugs has been widely reported. However, the role of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which catalyzes the conversion of inactive cortisone into active cortisol, in inflammation remains unclear. This study aimed to examine the mechanism of actions of 11β-HSD1 in lipopolysaccharide (LPS)-induced THP-1 cells. Materials and Methods: The gene expression of 11β-HSD1 and pro-inflammatory cytokines was detected via RT-PCR. The protein expression of IL-1β in cell supernatants was detected via ELISA. Oxidative stress and mitochondrial membrane potential were assessed using a reactive oxygen species (ROS) kit and a mitochondrial membrane potential (MMP) kit, respectively. The expression of Nuclear Factor- Kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) was detected via western blotting. Results: Elevated levels of 11β-HSD1 contributed to the expression of inflammatory cytokines, whereas BVT.2733, a selective 11β-HSD1 inhibitor, ameliorated inflammatory responses, ROS, and mitochondrial damage in LPS-stimulated THP-1 cells. Furthermore, cortisone and cortisol, which are the substrate and product of 11β-HSD1, respectively, showed biphasic responses and induced the expression of pro-inflammatory cytokines at a low concentration in both LPS-stimulated or untreated THP-1 cells. The enhanced inflammation was attenuated by co-treatment with BVT.2733 and the glucocorticoid receptor (GR) antagonist RU486, but not in those treated with the mineralocorticoid receptor (MR) antagonist spironolactone. Overall, the results indicate that 11β-HSD1 amplifies inflammatory responses by activating the NF-κB and MAPK signaling pathways. Conclusion: Inhibition of 11β-HSD1 may serve as a potential therapeutic target against the excessive activation of inflammation. | ||
| کلیدواژهها | ||
| 11β-Hydroxysteroid- dehydrogenase type 1؛ BVT.2733؛ Glucocorticoid Inflammation؛ THP-1 cells | ||
| مراجع | ||
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