Rituximab Attenuated Lipopolysaccharide-Induced Oxidative Cytotoxicity, Apoptosis, and Inflammation in the Human Retina Cells via Modulating the TRPM2 Signaling Pathways

Daldal H., NAZIROĞLU M.

OCULAR IMMUNOLOGY AND INFLAMMATION, 2022 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2022
  • Doi Number: 10.1080/09273948.2022.2075400
  • Title of Journal : OCULAR IMMUNOLOGY AND INFLAMMATION
  • Keywords: Apoptosis, ARPE-19 cells, human retina cells, lipopolysaccharide, oxidative stress, rituximab, TRPM2 channel, PIGMENT EPITHELIUM, CHANNEL, CD20, DEGENERATION, ACTIVATION, EXPRESSION, INDUCTION, STRESS, ENTRY, DEATH

Abstract

Purpose We investigated the possible protective effects of rituximab (RTX) on LPS-induced oxidant, inflammatory, and apoptotic adverse actions via the inhibition of TRPM2 channel in the adult retinal pigment epithelial-19 (ARPE-19) cells. Methods In the cultured ARPE-19 cells, we induced five main groups as control, RTX (10 mu g/ml), LPS (1 mu g/ml), LPS+RTX, and LPS+TRPM2 blockers (ACA or 2/APB). Results The levels of apoptosis, cell death, mitochondrial free reactive oxygen radicals (mitROS), cytosolic ROS, lipid peroxidation, caspase -3, caspase -8, caspase -9, ADP-ribose-induced TRPM2 current density, TNF-alpha, IL-1 beta, cytosolic free Zn2+, and Ca2+ were increased by LPS, although their levels were diminished by the treatments of RTX and TRPM2 blockers. Conclusions The LPS-induced mitROS, inflammatory cytokine, and apoptosis levels were modulated via TRPM2 inhibition in the human retinal epithelial cells by the RTX treatment. The RTX may be considered as a new therapeutic approach to LPS-induced human retinal epithelial cell injury.