Abstract
Chronic allograft nephropathy is manifested by inflammation and tubulointerstitial fibrosis. IL‐17A is a T‐cell‐derived cytokine upregulated in allograft nephropathy, therefore, the present study sought to characterize the actions of IL‐17A on human proximal tubule epithelium.First, pro‐fibrotic gene expression was examined by real‐time PCR in human proximal tubule cells following treatment with IL‐17A. e‐cadherin was significantly decreased while CTGF, CD44 and TGFβR1 were increased. These changes were reduced by anti‐IL‐17A antibody treatment. Next, IL‐17A‐stimulated soluble mediator secretion was examined. IL‐17A induced the secretion of fractalkine, G‐CSF, GM‐CSF, VEGF, IL‐6 and IL‐8. Finally, ZO‐1 expression was examined by immunocytochemistry as an indicator of epithelial integrity. Treatment with IL‐17A caused a substantial downregulation of ZO‐1 that was inhibited by anti‐IL‐17A antibody treatment.These data indicate IL‐17A can induce the upregulation of genes associated with ECM remodeling and cell‐cell interaction, and stimulate secretion of inflammatory mediators and immune cell chemoattractants. IL‐17A decreased ZO‐1 protein expression indicating it may negatively impact epithelial barrier function. Thus, IL‐17A may play an important role in the progression of chronic renal injury through the above‐described mechanisms. Centocor is a Johnson & Johnson company.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
