Regulation of Renal Transporters by Pro-inflammatory Cytokines in Human Proximal Tubular Epithelial Cells: Identification of the Perpetrator and Mechanisms.

ABSTRACT:

Introduction

Infection and inflammation elevate circulating pro-inflammatory cytokines that can affect renal drug clearance. Accordingly, we sought to (i) quantify the extent of modulation of renal drug-metabolizing enzymes and transporters (DMETs) by cytokines and (ii) identify the mechanism(s) underlying these effects.

Methods

Fresh primary human proximal tubular epithelial cells (PTECs) were cultured on extracellular matrix-coated Transwells. PTECs were exposed every 24 h, for 48 h, to IL-6, IL-1β, TNF-α, IFN-γ, IL-4, or IL-10 (0.1 or 1 ng/mL), individually or as a cocktail. mRNA expression of 25 renal DMETs was quantified by RT-qPCR. Individual activity of OAT1-4, OCT2, and OCTN1 was measured. To determine mechanisms of these effects, selective MAPK/NF-κB inhibitors (ERK

SUBMITTER: Tsang YP 

PROVIDER: S-EPMC12697364 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature