p38 MAPK regulates Th2 cytokines release in PBMCs in allergic rhinitis rats
Tóm tắt
Th2 cytokines play a pivotal role in the pathogenesis of allergic rhinitis. To investigate the effect of p38 mitogen-activated protein kinase (MAPK) on the production of Th2 cytokines such as IL-4 and IL-5 in allergic rhinitis, a model of allergic rhinitis was established in SD rats. The expression level of p38 MAPK mRNA in PBMCs was detected by means of real time quantitative RT-PCR. The p38 MAPK activity in PBMCs was detected by Western blotting. PBMCs were cultured with various concentrations of p38 MAPK inhibitor SB 239063 or without the treatment, and then IL-4, IL-5 levels of the supernatant were determined by using sandwich ELISA. The results showed that mRNA expression and activity of p38 MAPK in PBMCs were significantly higher in allergic rhinitis rats than in control rats (P<0.05). The p38 MAPK inhibitor SB 239063 decreased the production of IL-4 and IL-5 in a dose-dependent manner. It is concluded that p38 MAPK plays an important role in the pathogenesis of allergic rhinitis which is associated with Th2 cytokines release.
Tài liệu tham khảo
Weber RW. Allergic rhinitis. Prim Care, 2008,35(1):1–10, v
Dodeller F, Skapenko A, Kalden JR, et al. The p38 mitogen-activated protein kinase regulates effector functions of primary human CD4 T cells. Eur J Immunol, 2005,35(12):3631–3642
Dodeller F, Schulze-Koops H. The p38 mitogen-activated protein kinase signaling cascade in CD4 T cells. Arthritis Res Ther, 2006,8(2):205
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 2001,25(4): 402–408
Adachi T, Alam R. The mechanism of IL-5 signal transduction. Am J Physiol, 1998,275(3 Pt 1):C623–633
Wong WS, Leong KP. Tyrosine kinase inhibitors: a new approach for asthma. Biochim Biophys Acta, 2004, 1697(1–2):53–69
Liu Y, Shepherd EG, Nelin LD. MAPK phosphatases-regulating the immune response. Nat Rev Immunol, 2007,7(3):202–212
Mori A, Kaminuma O, Miyazawa K, et al. p38 mitogen-activated protein kinase regulates human T cell IL-5 synthesis. J Immunol, 1999,163(9):4763–4771
Koprak S, Staruch MJ, Dumont FJ. A specific inhibitor of the p38 mitogen activated protein kinase affects differentially the production of various cytokines by activated human T cells: dependence on CD28 signaling and preferential inhibition of IL-10 production. Cell Immunol, 1999,192(2):87–95
Duan W, Chan JH, McKay K, et al. Inhaled p38alpha mitogen-activated protein kinase antisense oligonucleotide attenuates asthma in mice. Am J Respir Crit Care Med, 2005,171(6):571–578
Grossman J. One airway, one disease. Chest, 1997,111(2 Suppl):11S–16S
Serrano C, Valero A, Picado C. Rhinitis and asthma: one airway, one disease. Arch Bronconeumol, 2005,41(10): 569–578
Underwood DC, Osborn RR, Kotzer CJ, et al. SB 239063, a potent p38 MAP kinase inhibitor, reduces inflammatory cytokine production, airways eosinophil infiltration, and persistence. J Pharmacol Exp Ther, 2000,293(1):281–288
Irusen E, Matthews JG, Takahashi A, et al. p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol, 2002, 109(4):649–657