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

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 13; p. 2461
• Main Authors: Shen, Chieh-Yu, Wu, Cheng-Han, Lu, Cheng-Hsun, Kuo, Yu-Min, Li, Ko-Jen, Hsieh, Song-Chou, Yu, Chia-Li
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.07.2019; MDPI
• Subjects: advanced glycation end products; Age; Aging; Alzheimer's disease; Amino Acids - metabolism; Animals; Apoptosis; Biomarkers; Carbohydrates; Cattle; Cytokines; Diabetes; Gene expression; Gene Expression Regulation - drug effects; Glycation End Products, Advanced - pharmacology; Glycoproteins - metabolism; Humans; IL-6; inflamm-aging; Inflammation; Interleukin-6 - genetics; Interleukin-6 - metabolism; Lectins; Lectins - metabolism; Maillard Reaction - drug effects; MAP Kinase Signaling System - drug effects; MAPK-ERK1/2; Molecular Weight; Monocytes - drug effects; Monocytes - metabolism; MyD88; Myeloid Differentiation Factor 88 - metabolism; NF-kappa B p50 Subunit - metabolism; NF-κB p50; Nε-(carboxymethyl)-lysine; Oxidative stress; Physiology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Serum Albumin, Bovine - pharmacology; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - metabolism; Th1 Cells - drug effects; Th1 Cells - metabolism; Th1/Th2 cytokines; Th2 Cells - drug effects; Th2 Cells - metabolism; inflamm-aging; MAPK-ERK1/2; Nε-(carboxymethyl)-lysine; Th1/Th2 cytokines; MyD88; advanced glycation end products; IL-6; NF-κB p50
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24132461

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.