Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area by producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-alpha dose-dependently induced the production of VEGF-C in HPTECs. The TNF-alpha-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NF kappa B. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-delta activator and reduced the TNF-alpha-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-delta-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-alpha induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-delta dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis. (C) 2014 Elsevier Inc. All rights reserved.