TRAIL, DR4 and DR5 Are Upregulated in Kidneys from Patients with Lupus Nephritis and Exert Proliferative and Proinflammatory Effects

Overview

Journal Clin Immunol

Specialty Allergy & Immunology

Date 2009 Apr 8

PMID 19349211

Citations 16

Authors

Vinh Nguyen

Cornelia Cudrici

Valentina Zernetkina

Florin Niculescu

Horea Rus

Cynthia Drachenberg

Violeta Rus

Affiliations

Soon will be listed here.

Abstract

We have previously reported that TRAIL is upregulated on T cells from patients with lupus and that T cell associated TRAIL enhances autoimmune parameters in a murine model of lupus. Whether TRAIL/TRAIL-R interaction plays a role in organ involvement such as lupus nephritis has not yet been assessed. We demonstrate here that TRAIL, DR4 and DR5 are upregulated in proximal and distal tubules of patients with proliferative lupus nephritis. In vitro, expression of TRAIL, DR4 and DR5 on primary proximal tubular epithelial cells (PTEC) was induced by TNFalpha and IFNgamma. Functionally, TRAIL did not induce apoptosis but rather enhanced the proliferation of PTEC through activation of PI3 kinase/AKT and ERK1/2, increased IL-8 production and upregulated ICAM-1 expression. These data demonstrate that cytokine induced upregulation of TRAIL, DR4 and DR5 in tubules from patients with proliferative lupus nephritis may play a protective role by enhancing PTEC survival while also exerting a proinflammatory effect that may contribute to local inflammation and injury.

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