Human renal epithelial cells produce the long pentraxin PTX3

Abstract

Pentraxin 3 (PTX3) is a prototypic long pentraxin with structural similarities in the C-terminal domain to the classical short pentraxins C-reactive protein (CRP) and serum amyloid P component. PTX3 is suggested to play an important role in the innate resistance against pathogens, regulation of inflammatory reactions, and clearance of apoptotic cells. Unlike the classic pentraxins, PTX3 is mainly expressed extrahepatically. The present study was designed to investigate the expression of PTX3 by human proximal renal tubular epithelial cells (PTECs). PTECs were cultured in the presence or absence of inflammatory cytokines. PTX3 mRNA expression was measured by reverse transcription-polymerase chain reaction (RT-PCR) in human kidney and PTECs. PTX3 protein levels in PTEC cultures were quantified by enzyme-linked immunosorbent assay (ELISA). PTX3 mRNA was shown to be constitutively expressed in human kidney. Constitutive expression and production of PTX3 was shown in primary mesangial cells, in primary PTECs, and in renal fibroblasts. Further analysis showed that interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha) stimulation strongly enhanced the expression and production of PTX3 in PTECs in a dose- and time-dependent manner. In addition, activation of PTECs with IL-17 and CD40L, respectively, but not with IL-6 or IL-4, resulted in strongly increased production of PTX3, whereas granulocyte macrophage-colony-stimulating factor (GM-CSF) inhibited IL-1-induced PTX3 production. PTX3 produced by PTEC is functionally active in binding C1q. These results indicate that PTX3 is expressed and released by PTECs and that in proinflammatory conditions PTX3 production is up-regulated. Local expression of PTX3 may play a role in the innate immune response and inflammatory reactions in the kidney.