Apocynin regulates cytokine production of CD8+ T cells

Seung Joo Nam, In Soo Oh, Young Ha Yoon, Bo In Kwon, Wonseok Kang, Hee Ja Kim, Seung Hoon Nahm, Youn Hee Choi, Seung Hyo Lee, Vito Racanelli, Eui Cheol Shin

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Apocynin is known to suppress the production of reactive oxygen species (ROS) by inhibiting NADPH oxidases, specifically phagocytic NADPH oxidase (PHOX or NOX2). Given the pro-inflammatory effects of ROS, apocynin has been studied extensively for its use as a therapeutic agent in various disease models. While the effects of apocynin on neutrophils and monocytes have been investigated, it remains to be elucidated whether apocynin modulates the effector function of T cells. In the present study, we examined the effect of apocynin on CD8 + T cells and further investigated its mechanism of action. We found that apocynin directly inhibited the production of pro-inflammatory cytokines such as TNF-α, IFN-γ, and IL-2 in anti-CD3/anti-CD28-stimulated CD8+ T cells. The action of apocynin was upstream of the protein kinase C and calcium signaling in the T cell receptor signaling pathway because apocynin did not inhibit cytokine production in phorbol 12-myristate 13-acetate/ionomycin-stimulated CD8+ T cells. Electrophoretic mobility shift assays revealed that apocynin attenuated anti-CD3/anti-CD28- induced NF-κB activation in CD8+ T cells. In the experiments with NOX2-deficient mice, we demonstrated that apocynin inhibited TNF-α production of CD8+ T cells in a NOX2-independent manner. Taken together, we demonstrated that apocynin, a well-known NOX2 inhibitor, suppressed the cytokine production of CD8+ T cells. We also showed the NOX2-independent action of apocynin in the inhibition of TNF-α production in CD8+ T cells.

Original languageEnglish
Pages (from-to)261-268
Number of pages8
JournalClinical and experimental medicine
Volume14
Issue number3
DOIs
StatePublished - Aug 2014

Keywords

  • Apocynin
  • NOX2
  • TNF-α

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