https://scholars.lib.ntu.edu.tw/handle/123456789/593946
標題: | Advanced Glycation End Products of Bovine Serum Albumin Suppressed Th1/Th2 Cytokine but Enhanced Monocyte IL-6 Gene Expression via MAPK-ERK and MyD88 Transduced NF-κB p50 Signaling Pathways | 作者: | CHIEH-YU SHEN CHENG-HAN WU CHENG-HSUN LU YU-MIN KUO KO-JEN LI SONG-CHOU HSIEH CHIA-LI YU |
關鍵字: | IL-6; MAPK-ERK1/2; MyD88; NF-κB p50; Nε-(carboxymethyl)-lysine; Th1/Th2 cytokines; advanced glycation end products; inflamm-aging | 公開日期: | 4-七月-2019 | 出版社: | MDPI | 卷: | 24 | 期: | 13 | 起(迄)頁: | 2461 | 來源出版物: | Molecules (Basel, Switzerland) | 摘要: | Advanced glycation end products (AGE), the most known aging biomarker, may cause "inflamm-aging" (i.e., chronic low-grade inflammation that develops with aging) in both aged and diabetes groups. However, the molecular bases of inflamm-aging remain obscure. We prepared AGE by incubating BSA (0.0746 mmol/L) + glucose (0.5 mol/L) at 37 °C in 5% CO2-95% air for 1-180 days. The lysine glycation in BSA-AGE reached 77% on day 30 and 100% after day 130, whereas the glycation of arginine and cysteine was minimal. The Nε-(carboxymethyl)-lysine content in BSA-AGE was also increased with increasing number of incubation days. The lectin-binding assay revealed that the glycation of BSA not only altered the conformational structure, but lost binding capacity with various lectins. An immunological functional assay showed that BSA-AGE > 8 μg/mL significantly suppressed normal human Th1 (IL-2 and IFN-γ) and Th2 (IL-10) mRNA expression, whereas AGE > 0.5 μg/mL enhanced monocyte IL-6 production irrelevant to cell apoptosis. The AGE-enhanced monocyte IL-6 production was via MAPK-ERK and MyD88-transduced NF-κBp50 signaling pathways. To elucidate the structure-function relationship of BSA-AGE-enhanced IL-6 production, we pre-preincubated BSA-AGE with different carbohydrate-degrading, protein-degrading, and glycoprotein-degrading enzymes. We found that trypsin and carboxypeptidase Y suppressed whereas β-galactosidase enhanced monocyte IL-6 production. In conclusion, BSA-AGE exerted both immunosuppressive and pro-inflammatory effects that are the molecular basis of inflamm-aging in aged and diabetes groups. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/593946 | ISSN: | 1420-3049 | DOI: | 10.3390/molecules24132461 | SDG/關鍵字: | advanced glycation end product; amino acid; bovine serum albumin; glycoprotein; immunoglobulin enhancer binding protein; interleukin 6; lectin; messenger RNA; myeloid differentiation factor 88; animal; bovine; drug effect; gene expression regulation; genetics; glycation; helper cell; human; MAPK signaling; metabolism; molecular weight; monocyte; Th1 cell; Th2 cell; Amino Acids; Animals; Cattle; Gene Expression Regulation; Glycation End Products, Advanced; Glycoproteins; Humans; Interleukin-6; Lectins; Maillard Reaction; MAP Kinase Signaling System; Molecular Weight; Monocytes; Myeloid Differentiation Factor 88; NF-kappa B p50 Subunit; RNA, Messenger; Serum Albumin, Bovine; T-Lymphocytes, Helper-Inducer; Th1 Cells; Th2 Cells |
顯示於: | 醫學系 |
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