In-vitro evidence indicating that IL-10 causes aging-related hypoalbuminemia via JAK1/STAT3 and CEBP-β

• Published in: Experimental cell research 2024-11, Vol.443 (1), p.114327, Article 114327
• Main Authors: Singh, Bharat, Kumari, Smita, Kureel, Amit Kumar, Saini, Sheetal, Prakash, Satya, Shah, Arunim, Chaturvedi, Chandra Prakash, Singh, Kulwant, Rai, Ambak Kumar
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aging; Aging - genetics; Aging - metabolism; Albumin; CCAAT-Enhancer-Binding Protein-beta - genetics; CCAAT-Enhancer-Binding Protein-beta - metabolism; CEBP-β/LIP; Female; Hep G2 Cells; Humans; Hypoalbuminemia; IL-10; Interleukin-10 - genetics; Interleukin-10 - metabolism; Janus Kinase 1 - genetics; Janus Kinase 1 - metabolism; Male; Middle Aged; Promoter Regions, Genetic - genetics; Signal Transduction; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism
• ISSN: 0014-4827; 1090-2422; 1090-2422
• DOI: 10.1016/j.yexcr.2024.114327

Albumin (ALB) has numerous vital physiological outcomes for healthy aging. A decrease in serum albumin, i.e., hypoalbuminemia, is one of the risk factors associated with aging, which affects physiological functioning. Hypoalbuminemia is the outcome of either decreased ALB synthesis or increased degradation. However, the potential mechanism controlling ALB's mRNA level expression in aged individuals is yet to be explored. We noted decreased serum ALB concentrations in aged individuals participating in our study, as compared to the young ones. We found that IL-10, a paradoxical inflammaging marker, reduced ALB concentration in HepG2 cells. Inhibiting the JAK/STAT3 signalling increased albumin mRNA suggesting its IL-10-driven regulation via JAK/STAT3 pathway. Albumin promotor analysis revealed the presence of a CEBP-β binding site. We showed that CEBP-β binds to the albumin promoter in an IL-10-dependent manner. Further, IL-10 increased the expressions of all CEBP-β isoforms, including the inhibitory isoform (LIP). The CEBP-β inhibition either by a functional inhibitor (i.e., quercetin) or shRNA silencing increased albumin mRNA in HepG2 cells. Our finding showed that IL-10 likely regulates albumin expression in a JAK/STAT3 and CEBP-β dependent manner in aging. A better understanding of the underlying condition can improve albumin protein levels and the well-being of the aged population. [Display omitted] •Hypoalbuminemia in aging is associated with various disease conditions.•Elevated levels of the anti-inflammatory cytokine IL-10 reduces albumin expression in HepG2 cells.•Inhibiting JAK/STAT3 signaling increases albumin expression.•IL-10 increases the expression of CEBP- β, which downregulates the expression of albumin.