C-reactive protein induced activation of MAP-K and RANTES in human renal distal tubular epithelial cells in vitro.

Abstract

AIMS:

C-reactive protein (CRP) is a component of the acute-phase reaction to inflammation, severe tissue injury, and infection. Investigations have shown that CRP concentration is highly increased in the urine during acute renal graft dysfunction and, therefore, may affect tubular cell metabolism. Nevertheless, no data about the effects of CRP on human renal tubular epithelial cells are available.

METHODS:

Human renal distal tubular cells (DTC) were isolated immunomagnetically and cultured. Cells were stimulated with affinity chromatography pure native CRP from human ascites (10 - 0.001 microg/ml). Phosphorylation of MAP-K was assessed by Westernblot analysis. Release of RANTES and interleukin-6 was evaluated with an enzyme immunoassay. Cytotoxic effects of CRP were determined by a commercially available Live/Dead assay and MTT assay. Effects on cell proliferation were analyzed by a fluorimetric assay.

RESULTS:

Westernblot analysis clearly showed that CRP activates the MAP-K pathway of DTC. CRP upregulated RANTES expression of DTC in a significant and dose-dependent manner. CRP (10 microg/ml) induced a 12.3-fold upregulation, CRP 1 or 0.1 microg/ml induced a 6.3-/2.8-fold RANTES upregulation, respectively. Interleukin-6 synthesis was not influenced. Cytotoxic, proliferative or apoptotic effects were not observed at the concentrations used.

CONCLUSIONS:

We demonstrated an activating effect of CRP on DTC in vitro. In vivo, this effect of CRP might be part of the immune activation cascade during episodes of renal graft rejection or bacterial infections.

• Authors: P C Baer, S Gauer, B Wegner, R Schubert, H Geiger
• Journal: Clinical nephrology (Clin Nephrol) Vol. 66 Issue 3 Pg. 177-83 (Sep 2006) ISSN: 0301-0430 [Print] Germany
• PMID: 16995340 (Publication Type: Journal Article)

Chemical References

• Chemokine CCL5
• Interleukin-6
• C-Reactive Protein
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• C-Reactive Protein (pharmacology)
• Cell Death (drug effects)
• Cell Survival (drug effects)
• Chemokine CCL5 (metabolism)
• Enzyme Activation (drug effects)
• Epithelial Cells (drug effects, enzymology, metabolism)
• Humans
• Interleukin-6 (metabolism)
• Kidney Tubules, Distal (drug effects, enzymology)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)