Preventative Administration Of Il-27 Improves Airway Inflammation Of Ovalbumin -Induced Asthma Mice Model Via Both Stat1 And Gadd45 gamma/p38mapk Pathways

Background: Interleukin-27 (IL-27) is a member of Th1 type cytokines, which could promote Th1 development and inhibit Th2. In this study, animal models were set up to observe whether IL-27 intervention could alleviate allergic airway inflammation and explore the related molecular mechanisms. Materials and Methods: We isolated and cultured CD4 + T cells from healthy people and mice to test whether IL-27 could inhibit IL-4 production by the cultured CD4 + T cells in different culture conditions; The effect of IL-27 was examined with two kinds of intra-nasal (i.n.) administration: one was low-dose-multiple-times prevention, the other was high-dose-few-times treatment in murine models of asthma; Expression levels of STAT1 and GADD45-γ/p38MAPK of lung tissue were measured by qPCR and Western Blot. Results: Preventative administration of IL-27 attenuated allergic inflammation and airway hyperreactivity obviously, while therapeutic administration of IL-27 had no significant effect. In asthma group, the phosphorylation of STAT1 was impaired while the GADD45γ and p38MAPK had no obvious change. Preventative administration of IL-27 could either reverse the impairment of STAT1 or strength the expression of GADD45γ and p38MAPK proteins while therapeutic administration of IL-27 had no significant effect. Conclusions: Preventative administration of IL-27 could improve the pathological changes of mouse asthma models via both STAT1 and GADD45γ/p38MAPK pathways while therapeutic administration of IL-27 has no significant effect which contribute to the already committed Th2-CD4+T cells existed in asthma airway which resist to the inhibition of IL-27.