Fatty acids bound to albumin have been reported to be involved in various responses in renal proximal tubular cells following albumin overload, leading to progression of tubulointerstitial damage in the kidneys. In addition, it has been reported that prostaglandin E-2 (PGE(2)) plays an important role in nephrotoxicity. The aim of this study was to examine whether albumin-bound fatty acids induce PGE(2) production in human renal proximal tubular epithelial cell line HK-2. Fatty acid-bearing human serum albumin increased PGE(2) release in the culture medium in concentration-dependent and time-dependent manners, but fatty acid-depleted albumin had no effect on PGE(2) production. Next, we investigated the effect of arachidonic acid, a precursor of eicosanoids, on PGE(2) production. Arachidonic acid with fatty acid-free albumin significantly enhanced the release of PGE(2) into the medium in a concentration dependent manner. Furthermore, we examined the effect of arachidonic acid on mRNA expression of hypoxia inducible factor-1 alpha (HIF-1 alpha). Arachidonic acid increased HIF-1 alpha mRNA expression in a concentration-dependent manner. These findings suggest that fatty acids, at least in part arachidonic acid, bound to albumin increase PGE(2) production and expression of HIF-1 alpha mRNA and protein, possibly resulting in various cell responses induced by albumin overload. (C) 2020 Elsevier Inc. All rights reserved.