Advanced glycation end products upregulate C-reactive protein synthesis by human hepatocytes through stimulation of monocyte IL-6 and IL-1 beta production.
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-1 beta (anti-IL-1 beta), or soluble IL-1 receptor and was completely inhibited when AGE-MCM were preincubated with anti-IL-6 and anti-IL-1 beta simultaneously. The inhibiting effect did not occur when AGE-MCM was preincubated with antibody of tumour necrosis factor-alpha (anti-TNF-alpha) and soluble TNF receptor. Exposure of HFH with exogenous IL-6 and IL-1 beta, at the same concentrations as contained in AGE-MCM, also increased CRP production, but exogenous TNF-alpha 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-1 beta production by human monocytes.
Li
J -T
J-
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Hou
F -F
F-
Guo
Z -J
Z-
Shan
Y -X
Y-
Zhang
X
X
Liu
Z -Q
Z-
D002097:C-Reactive Protein / Q000096:biosynthesis*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005333:Fetus; D015870:Gene Expression; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000503:physiopathology; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D017077:Culture Media, Conditioned; D017127:Glycation End Products, Advanced; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D002097:C-Reactive Protein