2. Academic Validation
  3. Glutathione Trisulfide Prevents Lipopolysaccharide-induced Inflammatory Gene Expression in Retinal Pigment Epithelial Cells

Glutathione Trisulfide Prevents Lipopolysaccharide-induced Inflammatory Gene Expression in Retinal Pigment Epithelial Cells

  • Ocul Immunol Inflamm. 2022 May 19;30(4):789-800. doi: 10.1080/09273948.2020.1833224.
Hiroshi Tawarayama 1 2,  Noriyuki Suzuki 1,  Maki Inoue-Yanagimachi 1,  Noriko Himori 1,  Satoru Tsuda 1,  Kota Sato 1 3,  Tomoaki Ida 4,  Takaaki Akaike 4,  Hiroshi Kunikata 1 2,  Toru Nakazawa 1 2 3 5 6
Affiliations

Affiliations

  • 1 Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • 2 Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • 3 Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • 4 Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • 5 Collaborative Program of Ophthalmic Drug Discovery, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • 6 Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
PMID: 33215957 DOI: 10.1080/09273948.2020.1833224
Abstract

We investigated the effects of glutathione trisulfide (GSSSG) on lipopolysaccharide (LPS)-induced inflammatory gene expression in immortalized ARPE-19, and primary human and mouse retinal pigment epithelial (RPE) cells. Sulfane sulfur molecules were significantly increased in GSSSG-treated ARPE-19 cells. GSSSG prevented the LPS-induced upregulation of interleukin (IL)-1β, IL-6, and C-C motif chemokine ligand 2 (CCL2) in ARPE-19/primary RPE cells. Moreover, GSSSG prevented the activation of the nuclear factor-kappa B p65 subunit, and promoted the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in LPS-treated ARPE-19 cells. ERK1/2 inhibition prevented the GSSSG-mediated inhibition of LPS-induced IL-6 and CCL2 upregulation. Additionally, ERK1/2 activation prevented the upregulation of these genes in the absence of GSSSG. Knockdown of HMOX1 or NRF2, known as anti-oxidative genes, did not affect the activity of GSSSG in the context of LPS stimulation. These findings suggest that GSSSG attenuates LPS-induced inflammatory gene expression via ERK signaling hyperactivation, independently of the NRF2/HMOX1 pathway.

Keywords

Reactive persulfide species; anti-inflammation; antioxidants; glutathione trisulfide.

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