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Areca nut extract suppresses T-cell activation and interferon-gamma production via the induction of oxidative stress
1Department of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan, ROC.
Abstract:
Areca quid chewing is a major risk factor associated with oral submucous fibrosis (OSF) and oral cancer. Experimental evidence indicates that immune deterioration is associated with the pathophysiology of OSF and oral cancer. In addition, reactive oxygen species (ROS) is shown to play a role in the cytotoxic and genotoxic effect induced by areca nut extracts (ANE) in oral cells. The present studies investigated the effects of ANE on T-cell reactivity and the role of ROS in ANE effects. Treatment of splenocytes with ANE induced a marked cytotoxic effect, and suppressed the production of IL-2 and IFN-gamma, whereas the production of IL-4 was unaffected. The ANE-mediated cytotoxicity, and suppression of IFN-gamma and IL-2 production were attenuated by the presence of antioxidant N-acetyl-l-cysteine (NAC). Moreover, flow cytometric analysis demonstrated an increase in cellular ROS levels in splenic T-cells treated with ANE, which was also attenuated by the presence of NAC. Concordantly, the cellular level of glutathione was diminished by ANE in splenic T-cells pretreated with NAC. Collectively, these results demonstrated that ANE markedly suppressed T-cell activation and Th1 cytokine production, which was mediated, at least in part, by the induction of oxidative stress.
Insights
Areca nut extracts (ANE) suppress immune T-cells and reduce vital cytokine production, contributing to oral cancer risk. Antioxidants like N-acetyl-l-cysteine (NAC) can mitigate these harmful effects by reducing oxidative stress.
Area of Science:
- Oral pathology
- Immunology
- Oxidative stress research
Background:
- Areca quid chewing is a significant risk factor for oral submucous fibrosis (OSF) and oral cancer.
- Immune dysfunction and oxidative stress are implicated in OSF and oral cancer development.
- Areca nut extracts (ANE) exhibit cytotoxic and genotoxic effects on oral cells.
Purpose of the Study:
- To investigate the impact of ANE on T-cell reactivity.
- To determine the role of reactive oxygen species (ROS) in ANE-induced effects on T-cells.
Main Methods:
- Splenocytes were treated with ANE.
- Cytokine production (IL-2, IFN-gamma, IL-4) was measured.
- Cellular ROS levels and glutathione content were assessed using flow cytometry.
- The effects of the antioxidant N-acetyl-l-cysteine (NAC) were evaluated.
Main Results:
- ANE induced significant cytotoxicity and suppressed IL-2 and IFN-gamma production in splenocytes.
- ANE treatment increased ROS levels in splenic T-cells.
- The antioxidant NAC attenuated ANE-induced cytotoxicity, suppressed cytokine production, and reduced ROS levels.
- ANE diminished cellular glutathione levels, an effect reversed by NAC pretreatment.
Conclusions:
- Areca nut extracts markedly suppress T-cell activation and Th1 cytokine production.
- Oxidative stress, induced by ANE, plays a key role in mediating these suppressive effects on T-cells.
- Antioxidant intervention may offer a protective strategy against ANE-induced immunotoxicity.
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