[Effects of C-reactive protein on the expression of transforming growth factor ß1 and receptors on human renal tubular epithelial cells].

OBJECTIVE: To explore the effect of C-reactive protein (CRP) on the expression of Fcγ receptors in human renal tubular epithelial cells and determine the role of Fcγ receptors in CRP-induced expression of transforming growth factor ß1 (TGFß1). METHODS: Human renal tubular epithelial cells (HK-2) were cultured and stimulated with recombinant human CRP. The mRNA expression of Fcγ receptors, including FcγRI (CD64), FcγRIIa (CD32a) and FcγRIII (CD16), was detected by real-time polymerase chain reaction (PCR). On the basis of real-time PCR results, CD32a was selected for further analysis: the CD32a expression in HK-2 cells incubated with 10 mg/L CRP for 24 h was determined by flow cytometry and Western blotting. HK-2 cells were preincubated with or without anti-CD32a IgG, followed by the addition of recombinant human CRP. Subsequently the biological effects of CRP were tested. TGFß1, type I collagen (ColI) and type IV collagen (ColIV) released into media were detected by enzyme-linked immunosorbent assay. And TGFß1 mRNA expression was measured by real-time PCR. RESULTS: On real-time PCR, CRP was found to significantly up-regulate the CD32a mRNA expression in HK-2 cells in a dose-dependent manner (P < 0.01). The peak up-regulation was observed at a dose of 10 mg/L. In contrast, mRNAs of CD16 and CD64 were not detected in HK-2 cells. Flow cytometry showed that CD32a expressed on HK-2 cells incubated with 10 mg/L recombinant human CRP for 24 h accounted for 23.35% ± 7.43%, significantly higher than that on non-CRP-treated cells (1.66% ± 0.28%, P < 0.01). Western blotting showed that CRP up-regulated CD32a expression in a dose-dependent manner. And 10 mg/L CRP induced the peak effect. Antibodies to CD32a inhibited the stimulatory effect of CRP on the generation of TGFß1, ColI and ColIV (all P < 0.05) and down-regulated the expression of TGFß1 mRNA (P < 0.01). CONCLUSION: The stimulation of CRP can significantly increase CD32a expression in renal tubular epithelial cells and up-regulate the expression of transforming growth factor TGFß1 through CD32a receptor.

Expression of soluble Toll-like receptors in pleural effusions.

BACKGROUND: The Toll-like receptors (TLRs) represent a group of single-pass transmembrane receptors expressed on sentinel cells that are central to innate immune responses.The aim of this study was to investigate the presence of soluble TLRs in pleural effusions, and the diagnostic values of TLRs for pleural effusion with various etiologies. METHODS: Pleural effusion and serum samples were collected from 102 patients (36 with malignant pleural effusion, 36 with tuberculous pleural effusion, 18 with bacterial pleural effusion, and 12 with transudative pleural effusion). The concentrations of TLR1 to TLR10 were determined in effusion and serum samples by enzyme linked immunosorbent assay. Four classical parameters (protein, lactate dehydrogenase, glucose and C-reactive protein (CRP)) in the pleural fluid were also assessed. Receiver-operating characteristic curves were used to assess the sensitivity and specificity of pleural fluid TLRs and biochemical parameters for differentiating bacterial pleural effusion. RESULTS: The concentrations of TLR1, TLR3, TLR4, TLR7 and TLR9 in bacterial pleural effusion were significantly higher than those in malignant, tuberculous, and transudative groups, respectively. Analysis of receiver operating characteristic curves revealed that the area under the curves of TLR1, TLR3, TLR4, TLR7 and TLR9 were 0.831, 0.843, 0.842, 0.883 and 0.786, respectively, suggesting that these TLRs play a role in the diagnosis of bacterial pleural effusion. Also, the diagnostic value of TLRs for bacterial pleural effusions was much better than that of biochemical parameters (protein, lactate dehydrogenase, glucose and CRP). CONCLUSIONS: The concentrations of TLR1, TLR3, TLR4, TLR7 and TLR9 appeared to be increased in bacterial pleural effusion compared to non-bacterial pleural effusions. Determination of these pleural TLRs may improve the ability of clinicians to differentiate pleural effusion patients of bacterial origin from those with other etiologies.