Premium
Advanced Glycation End Products Upregulate C‐reactive Protein Synthesis by Human Hepatocytes Through Stimulation of Monocyte IL‐6 and IL‐1β Production
Author(s) -
Li J.T.,
Hou F.F.,
Guo Z.J.,
Shan Y.X.,
Zhang X.,
Liu Z.Q.
Publication year - 2007
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2007.02001.x
Subject(s) - glycation , receptor , endocrinology , medicine , chemistry , tumor necrosis factor alpha , stimulation , monocyte , downregulation and upregulation , interleukin 6 , albumin , c reactive protein , interleukin , cytokine , immunology , andrology , inflammation , biochemistry , gene
Patients with chronic renal failure are characterized by increased plasma levels of C‐reactive protein (CRP) and advanced glycation end products (AGE). AGE have been identified as a class of proinflammator mediators. To investigate whether AGE can stimulate hepatocytes to produce CRP, primary human fetal hepatocytes (HFH) were incubated with AGE‐modified human serum albumin (AGE‐HSA) or conditioned medium from AGE‐HSA‐stimulated monocytes (AGE‐MCM). CRP concentrations in the supernatants were determined by an ELISA and CRP mRNA levels were determined by a quantitative RT‐PCR. Exposure of HFH with AGE‐HSA for 12–72 h did not change CRP concentrations in the supernatants. CRP protein and mRNA expression were significantly upregulated in a time‐ and dose‐dependent manner when HFH were incubated with AGE‐MCM. This stimulating effect was partially inhibited when AGE‐MCM were preincubated with antibodies against interleukin‐6 (anti‐IL‐6), interleukin‐1β (anti‐IL‐1β), or soluble IL‐1 receptor and was completely inhibited when AGE‐MCM were preincubated with anti‐IL‐6 and anti‐IL‐1β simultaneously. The inhibiting effect did not occur when AGE‐MCM was preincubated with antibody of tumour necrosis factor‐α (anti‐TNF‐α) and soluble TNF receptor. Exposure of HFH with exogenous IL‐6 and IL‐1β, at the same concentrations as contained in AGE‐MCM, also increased CRP production, but exogenous TNF‐α had no effect. These results suggest that AGE cannot directly stimulate hepatocytes to produce CRP, but rather indirectly enhance CRP expression via stimulation of IL‐6 and IL‐1β production by human monocytes.