A novel regulatory mechanism of naringenin through inhibition of T lymphocyte function in contact hypersensitivity suppression.
Naringenin, a flavonoid in grapefruits and citrus fruits, has been reported to exhibit anti-inflammatory and anti-oxidative activities. Contact hypersensitivity (CHS) is a T cell-mediated immune reaction, and the factors released from macrophages also contribute to this response. Previous studies showed that naringenin suppressed CHS by inhibiting activation and migration of macrophages. However, little is known about naringenin's effects on T lymphocytes. Our study indicated that naringenin potently suppressed picryl chloride (PCl)-induced contact hypersensitivity by inhibiting the proliferation and activation of T lymphocytes. In vitro, both of the activated hapten-specific T cells and the T cells stimulated with anti-CD3/anti-CD28 showed growth arrest after naringenin treatment. Furthermore, naringenin reduced CD69 (the protein level) and cytokines such as IL-2, TNF-alpha, and IFN-gamma (the mRNA level) expressions which highly expressed by activated T cells. Meanwhile, naringenin also induced T cell apoptosis by upregulation of Bax, Bad, PARP, cleaved-caspase 3 and downregulation of phosphorylated Akt, Bcl-2. These findings suggest that, besides its anti-inflammatory activities in macrophages, naringenin also showed inhibitory effects on the activation and proliferation of T cells to alleviate symptoms of contact hypersensitivity.
Fang
Feng
F
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
Tang
Yijun
Y
Gao
Zhe
Z
Xu
Qiang
Q
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors; D003877:Dermatitis, Contact / Q000276:immunology*; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*; D000099192:CD69 Antigens
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000975:Antioxidants; D016207:Cytokines; D044950:Flavanones; D037181:Lectins, C-Type; D000099192:CD69 Antigens; C005273:naringenin