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- Title
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.
- Authors
Shen, Chieh-Yu; Wu, Cheng-Han; Lu, Cheng-Hsun; Kuo, Yu-Min; Li, Ko-Jen; Hsieh, Song-Chou; Yu, Chia-Li; Tanaka, Hidenori
- Abstract
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.
- Subjects
ADVANCED glycation end-products; MONOCYTES; SERUM albumin; GENE expression
- Publication
Molecules, 2019, Vol 24, Issue 13, p2461
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules24132461