title: Apocynin regulates cytokine production of CD8(+) T cells.
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.
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, 291 Daehak-ro, Daejeon, 305-701, Korea.
authors.forename: Seung-Joo
authors.initials: SJ
authors.lastname: Nam
authors.forename: In Soo
authors.initials: IS
authors.lastname: Oh
authors.forename: Young Ha
authors.initials: YH
authors.lastname: Yoon
authors.forename: Bo In
authors.initials: BI
authors.lastname: Kwon
authors.forename: Wonseok
authors.initials: W
authors.lastname: Kang
authors.forename: Hee Ja
authors.initials: HJ
authors.lastname: Kim
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Nahm
authors.forename: Youn-Hee
authors.initials: YH
authors.lastname: Choi
authors.forename: Seung-Hyo
authors.initials: SH
authors.lastname: Lee
authors.forename: Vito
authors.initials: V
authors.lastname: Racanelli
authors.forename: Eui-Cheol
authors.initials: EC
authors.lastname: Shin
mesh_terms: D000098:Acetophenones / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008810:Mice, Inbred C57BL
chemical_list: D000098:Acetophenones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; C056165:acetovanillone