Progress on the role of 11β-HSD1 in inflammation,development of hepatocellular carcinoma and immunity

doi:10.16352/j.issn.1001-6325.2023.05.0837

Abstract

Abstract: The 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) with anti-inflammatory or pro-inflammatory effects in inflammatory diseases is related to metabolism, as well as in the immune response through regulatpn of glucocorticoid (GC) synthesis. The expression and functional activity of 11β-HSD1 are potentially induced by pro-inflammatory cytokines, this process relies on the NF-κB signaling pathway and is ultimately determined by the utilization levels of HSD11B1 P1 and P2 promoters. In addition, 11β-HSD1 inhibits the proliferation of hepatocellular carcinoma by reducing glucose intake and glycolysis in hepatocellular carcinoma, and thus plays a role in the development of T cells in thymus and the form of angiogenesis by regulating the level of GC. Understanding the molecular regulatory mechanism of 11β-HSD1 in inflammatory diseases, carcinogenesis, development and immune response is conducive to exploring the occurrence and development of related diseases.

Key words: 11β-hydroxysteroid dehydrogenase 1(11β-HSD1), inflammation, carcinogenesis, immunity

CLC Number:

LEI Xingyu, FENG Xuesong, CHAO Xu. Progress on the role of 11β-HSD1 in inflammation,development of hepatocellular carcinoma and immunity[J]. Basic & Clinical Medicine, 2023, 43(5): 837-841.

References

[1]Chedid MF, Do NF, de Oliveira FS, et al. Interaction of HSD11B1 and H6PD polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional study[J]. Diabetol Metab Syndr, 2019,11:78.doi: 10.1186/s13098-019-0474-2.
[2]Huang P, Li Y, Xu C, et al. HSD11B1 is upregulated synergistically by IFNγ and TNFα and mediates TSG-6 expression in human UC-MSCs[J].Cell Death Discov, 2020,6:24. doi: 10.1038/s41420-020-0262-7.
[3]Ballegeer M, Van Looveren K, Timmermans S, et al. Glucocorticoid receptor dimers control intestinal STAT1 and TNF-induced inflammation in mice[J]. J Clin Invest, 2018,128:3265-3279.
[4]Han D, Yu Z, Zhang H, et al. Microenvironment-associated gene HSD11B1 may serve as a prognostic biomarker in clear cell renal cell carcinoma: a study based on TCGA, RT-qPCR, Western blotting, and immunohistochemistry[J]. Bioengineered, 2021,12:10891-10904.
[5]Verma M, Kipari T, Zhang Z, et al. 11β-hydroxysteroid dehydrogenase-1 deficiency alters brain energy metabolism in acute systemic inflammation[J]. Brain Behav Immun,2018,69:223-234.
[6]Gomez-Sanchez EP, Gomez-Sanchez CE. 11β-hydroxysteroid dehydrogenases: a growing multi-tasking family[J]. Mol Cell Endocrinol,2021,526:111210. doi: 10.1016/j.mce.2021.111210.
[7]Lee NR, Kim BJ, Lee CH, et al. Role of 11β-hydroxysteroid dehydrogenase type 1 in the development of atopic dermatitis[J]. Sci Rep, 2020,10:20237.doi: 10.1038/s41598-020-77281-x.
[8]Oróstica L, Astorga I, Plaza-Parrochia F, et al. Proinflammatory environment and role of TNF-ɑ in endometrial function of obese women having polycystic ovarian syndrome[J]. Int J Obes (Lond), 2016,40:1715-1722.
[9]Hu M, Zhang Y, Guo X, et al. Perturbed ovarian and uterine glucocorticoid receptor signaling accompanies the balanced regulation of mitochondrial function and NFκB-mediated inflammation under conditions of hyperandrogenism and insulin resistance[J]. Life Sci, 2019, 232:116681. doi: 10.1016/j.lfs.2019.116681.
[10]李博然, 马璐璐, 申乐, 等. NF-κB信号通路在子宫内膜异位症疼痛中作用的研究进展[J]. 基础医学与临床,2018,38:4. doi: 10.3969/j.issn.1001-6325.2018.10.022.
[11]Thomas AE, Inagadapa P, Jeyapal S, et al. Maternal magnesium restriction elevates glucocorticoid stress and inflammation in the placenta and fetus of WNIN rat dams[J]. Biol Trace Elem Res, 2018,181:281-287.
[12]Verma M, Kipari T, Zhang Z, et al. 11β-hydroxysteroid dehydrogenase-1 deficiency alters brain energy metabolism in acute systemic inflammation[J]. Brain Behav Immun, 2018,69:223-234.
[13]Sattler J, Tu J, Stoner S, et al. Role of 11β-HSD type 1 in abnormal HPA axis activity during immune-mediated arthritis[J]. Endocr Connect, 2018,7:385-394.
[14]Vagnerová K, VodiŠka M, Hermanová P, et al. Interactions between gut microbiota and acute restraint stress in peripheral structures of the hypothalamic-pituitary-adrenal axis and the intestine of male mice[J]. Front Immunol, 2019,10:2655. doi: 10.3389/fimmu.2019.02655.
[15]Ergang P, Vagnerová K, Hermanová P, et al. The gut microbiota affects corticosterone production in the murine small intestine[J]. Int J Mol Sci, 2021,22:4229. doi: 10.3390/ijms22084229.
[16]Wu Y, Zhou BP. TNF-alpha/NF-kappaB/Snail pathway in cancer cell migration and invasion[J]. Br J Cancer, 2010,102:639-644.
[17]Liu X, Tan XL, Xia M, et al. Loss of 11βHSD1 enhances glycolysis, facilitates intrahepatic metastasis, and indicates poor prognosis in hepatocellular carcinoma[J]. Oncotarget, 2016,7:2038-2053.
[18]Wang C, Yu S, Qian R, et al. Prognostic and immunological significance of peroxisome proliferator-activated receptor gamma in hepatocellular carcinoma based on multiple databases[J]. Transl Cancer Res, 2022,11:1938-1953.
[19]Flannery PC, Abbott KL, Pondugula SR. Correlation of PPM1A downregulation with CYP3A4 repression in the tumor liver tissue of hepatocellular carcinoma patients[J]. Eur J Drug Metab Pharmacokinet, 2020,45:297-304.
[20]Khamis ZI, Pang X, Cui Z, et al. Cytochrome P450-2D6: a novel biomarker in liver cancer health disparity[J]. PLoS One, 2021,16:e257072. doi: 10.1371/journal.pone.0257072.
[21]Oliveira-de-Abreu E, Silva-Dos-Santos D, Lepletier A, et al. Lack of galectin-3 disrupts thymus homeostasis in association to increase of local and systemic glucocorticoid levels and steroidogenic machinery[J]. Front Endocrinol (Lausanne), 2018,9:365. doi: 10.3389/fendo.2018.00365.
[22]Rocamora-Reverte L, Reichardt HM, Villunger A, et al. T-cell autonomous death induced by regeneration of inert glucocorticoid metabolites[J]. Cell Death Dis, 2017,8:e2948. doi: 10.1038/cddis.2017.344.
[23]Zhang Z, Coutinho AE, Man TY, et al. Macrophage 11β-HSD-1 deficiency promotes inflammatory angiogenesis[J]. J Endocrinol, 2017,234:291-299.
[24]Wu J, Miller E, Davidson C, et al. Enhanced angiogen-esis by 11βHSD1 blockage is insufficient to improve reperfusion following hindlimb ischaemia[J]. Front Cardiovasc Med, 2021,8:795823. doi: 10.3389/fcvm.2021.795823.
[25]Shimada-Omori R, Yamasaki K, Koike S, et al. TLR3 augments glucocorticoid-synthetic enzymes expression in epidermal keratinocytes; implications of glucocorticoid metabolism in rosacea epidermis[J]. J Dermatol Sci, 2020,100:58-66.