Tissue kallikrein mediates pro-inflammatory pathways in proximal tubular epithelial cells

Abstract

BACKGROUND: Tissue kallikrein (KLK1) expression is up-regulated in human diabetic kidney tissue. Since the kallikrein-kininsystem (KKS) has been linked to cellular inflammatory process in many diseases, we explore the role of KLK1 in tubular pro-inflammatory responses under the diabetic milieu. METHODS: Human proximal tubular epithelial cells (PTEC) were incubated with recombinant KLK1 protein to examine the expression of pro-inflammatory cytokines and the activation of signaling pathways. Cells were then transfected with KLK1-specific or control siRNA to investigate the effect of KLK1 on advanced glycation end products (AGE)-induced pro-inflammatory responses. RESULTS: Recombinant KLK1 stimulated the production of inflammatory cytokines including IL-8, ICAM-1 and CCL-2, and activated the phosphorylation of p42/44 and p38 MAPK in PTEC. Increased expression of KLK1 was detected in PTEC stimulated with AGE (0.5 mg/ml), and molecular knockdown of endogenous KLK1 expression attenuated AGE-induced tubular IL-8 and ICAM-1 productions. CONCLUSIONS: Our data suggest for the first time that KLK1 mediates pro-inflammatory responses in renal tubule cells under a diabetic milieu, and pave the way for further investigation that targets KLK1 in ameliorating diabetic tubular injury.