Elsevier

Cytokine

Volume 9, Issue 3, March 1997, Pages 178-186
Cytokine

Regular article
MODULATION OF IL-1-INDUCED CHEMOKINE EXPRESSION IN HUMAN MESANGIAL CELLS THROUGH ALTERATIONS IN REDOX STATUS

https://doi.org/10.1006/cyto.1996.0152Get rights and content

Abstract

The effects of altering intracellular redox potential on interleukin 1 (IL-1)-induced MCP-1 gene expression by human mesangial cells were examined. Thiol containing antioxidants significantly increased cellular glutathione content while decreasing glutathione disulfide levels. These antioxidants inhibited IL-1 induction of MCP-1 mRNA expression. This correlated with a decrease in DNA binding activity of NFκB, a transcription factor thought to be necessary for MCP-1 gene expression Incubation of mesangial cells with the oxidizing agents diamide or hydrogen peroxide did not upregulate MCP-1 gene expression, and prevented IL-1 induction of MCP-1 mRNA. Oxidants appeared to inhibit the degradation of IκB, and the translocation of NF-κB to the nucleus. Non-oxidative depletion of intracellular glutathione also attenuated the effects of IL-1 on MCP-1 expression. These data indicate that the intracellular redox potential is a critical determinant of cell activation by IL-1. The observation that both oxidizing and reducing environments are inhibitory suggests that redox changes can affect the IL-1 signal tranduction pathway at multiple points.

References (0)

Cited by (60)

  • The natural product bergenin ameliorates lipopolysaccharide-induced acute lung injury by inhibiting NF-kappaB activition

    2017, Journal of Ethnopharmacology
    Citation Excerpt :

    Elevated IL-1β, TNF-a and IL-6 in plasma is predictive of clinical outcome (Cross and Matthay, 2011; Meduri et al., 1995). Furthermore, IL-1β can induce lung fibrosis and release of a variety of chemokines, including monocyte chemotatic protein-1(MCP-1), Macrophage inflammatory protein-1 alpha (MIP-1α) (Rovin et al., 1997). IL-1β also alters the permeability of pulmonary blood vessels and enhances the recruitment of inflammatory cells into alveolar, resulting in pulmonary edema formation (Olman et al., 2002).

  • Functional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction

    2012, Free Radical Biology and Medicine
    Citation Excerpt :

    Systemic oxidative stress was also accompanied by increased expression of proinflammatory cytokines and chemokines. The mechanisms that trigger the production of inflammatory cytokines and chemokines in FSHD are unknown, but they are likely related to GSSG accumulation [69–71]. Accordingly, TNF-α increase was significantly correlated with the plasma concentration of GSSG (rho=0.62; P=0.02), which is involved in the induction of proinflammatory responses, such as increased TNF-α release [72].

  • The impact of redox and thiol status on the bone marrow: Pharmacological intervention strategies

    2011, Pharmacology and Therapeutics
    Citation Excerpt :

    However, such studies are likely to be complicated by the pleiotropic effects of many cytokines when placed in a specialized environment. ( Jeannin et al., 1995; Rovin et al., 1997; Gosset et al., 1999; Haddad, 2002) The utility of agents such as NAC, NOV-002, and free thiol containing drugs in directing T cell and APC cytokine production has potential therapeutic utility in patients undergoing immunosuppressive treatments.

  • Interplay among oxidants, antioxidants, and cytokines in skin disorders: Present status and future considerations

    2007, Biomedicine and Pharmacotherapy
    Citation Excerpt :

    Valacchi's group also showed that in the cytoplasm, BPO interacted with the water soluble antioxidants, resulting in GSH depletion and a decrease in the intracellular GSH/GSSG ratio which reflects the redox state of the cells [112,113]. The fluctuation in the cell redox environment induced the gene expression of pro-inflammatory cytokines including IL-1, Il-6, TNFα, and IL-8 [114,115] Hence, there is a possibility that antioxidant supplementation may improve or even avoid the potential deleterious effects of the therapeutical agent. The possibility that microorganisms, which constitute the normal flora in the skin (mainly Staphylococcus species) might also contribute to cell damage resulting from a synergy between their toxins and pro-inflammatory agents generated by activated leukocytes, oxidants and cytokines, should be considered.

View all citing articles on Scopus
f1

Correspondence to: Brad H. Rovin, Nephrology Division, Ohio State University, 1654 Upham Dr., Columbus, OH 43210, USA

View full text