https://scholars.lib.ntu.edu.tw/handle/123456789/634819
標題: | Unveiling the molecular basis of inflamm-aging induced by advanced glycation end products (AGEs)-modified human serum albumin (AGE-HSA) in patients with different immune-mediated diseases | 作者: | CHIEH-YU SHEN KO-JEN LI CHENG-HAN WU CHENG-HSUN LU YU-MIN KUO SONG-CHOU HSIEH CHIA-LI YU |
關鍵字: | AGE-modified human serum albumin; Immune-mediated diseases; Inflamm-aging; N(e)-carboxyethyl-lysine; N(e)-carboxymethyl-lysine; Senescence-associated β-galactosidase | 公開日期: | 七月-2023 | 卷: | 252 | 起(迄)頁: | 109655 | 來源出版物: | Clinical immunology (Orlando, Fla.) | 摘要: | Increased serum advanced glycation end products (AGEs) are commonly found in the patients with Diabetes mellitus (DM), aging-related diseases, and immune-mediated diseases. These diseases are notorious for vasculopathy, immune dysfunctions, and low-grade inflammation mimicking inflamm-aging. However, the molecular basis of inflamm-aging related to AGEs remains elucidation. In this study, we incubated human serum albumin (HSA) and glucose at 37 °C in 5% CO2 incubator for 0-180 days to generate AGE-HSA. We found the mixture gradually changing the color from transparancy to brown color and increased molecular weight during incubation. The pH value also gradually decreased from 7.2 to 5.4 irrelevant to ionic charge or [Ca2+] concentration, but dependent on gradual glycation of the alkaline amino acids, lysine and arginine. Functionally, 40 μg/mL of AGE-HSA decreased IL-2 production from human Jurkat T cell line via suppressing p-STAT3, p-STAT4, and p-STAT6 with an increased tendency of senescence-associated β-galactosidase (SA-βgal) expression but irrelevant to change of Th1/Th2/Treg subpopulations. In contrast, AGE-HSA enhanced CC motif chemokine ligand 5 (CCL-5), IL-8, macrophage migration inhibitor factor (MIF), and interleukin 1 receptor antagonist (IL-1Ra) but suppressed SA-βgal expression by human macrophage-like THP-1 cells. Interestingly, AGE-HSA abrogated the HSA-induced soluble intercellular adhesion molecules 1 (sICAM-1), sE-selectin and endothelin release from human coronary artery endothelial cells (HCAEC) and enhanced SA-βgal expression. The accelerated and increased HSA glycations by individual inflammation-related cytokine such as IL-2, IL-6, IL-17, TGF-β, or TNF-α in the in vitro study reflect increased serum AGE levels in patients with immune-mediated diseases. In conclusion, AGE-HSA can exert immunosuppresive, inflammatory and vasculopathic effects mimicking inflamm-aging in these patients. |
URI: | https://www.scopus.com/record/display.uri?eid=2-s2.0-85161009050&origin=resultslist&sort=plf-f https://scholars.lib.ntu.edu.tw/handle/123456789/634819 |
ISSN: | 15216616 | DOI: | 10.1016/j.clim.2023.109655 |
顯示於: | 醫學系 |
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