| Objective：（1）To establish a model of allergic rhinitis in rat.（2）To observe the expression of TLR2in rat nasal tissues and human nasalepithelial cells HNEpC.（3）To evaluate the effect of peptidoglycan (PTG) and pyrrolidinedithi-ocarbamic acid (PDTC) on the expression of IFN-β, IgE, IκB, IRAK-1,MyD88, IL-1, IL-6, NF-κB, TLR2, TNF-β and TRAF-6.（4）To investigate the role of TLR2in TLR2-NF-κB signaling pathway.（5）To investigate the efficacy of triptolide (TP) on AR and theintervention on TLR2-NF-κB signaling pathway.Methods:（1） The model of allergic rhinitis in rat was established usingintraperitoneal injection and intranasal drop of ovalbumin (OVA).（2） Human nasal epithelial cells HNEpC were cultured normally,peptidoglycan (PTG) and Pyrrolidinedithiocarbamic acid (PDTC) were usedto activate TLR2and inhibit NF-κB respectively.（3）Cytokines such as IFN-β, IgE, IκB, IRAK-1, MyD88, IL-1, IL-6, NF-κB,TLR2, TNF-β and TRAF-6in rat nasal tissues and human nasal epithelialcells HNEpC were observed by immunohistochemistry andimmunocytochemistry.（4）The levels of mRNA were evaluated by Real-Time PCR.（5）The levels of protein were evaluated by Western Blot.（6）Rats were treated with triptolide (TP) by intraperitoneal injection of30mg/kg·d before sensitization, and the effect of TP on allergicrhinitis symptoms and TLR2-NF-κB signaling pathway in rats were thenevaluated.Results:（1）The model of allergic rhinitis in rat was established successfullyusing intraperitoneal injection and intranasal drop of OVA.（2）The expression of TLR2and NF-κB in nasal tissues increasedsignificantly in rat with allergic rhinitis. PTG increased the expressionof both TLR2and NF-κB, whereas PDTC only decreased the expression ofNF-κB but not TLR2.（3）The expression of those cytokines mentioned above in group model,group PTG and group PDTC in rat nasal tissues were higher than those incontrol. And the expression of almost all of those cytokines in group PTGwere higher than those in group model and group PDTC except IFN-β. Theexpression of MyD88, IRAK-1, TRAF-6and TLR2in group PDTC was nearly thesame as group model, while the expression of IgE, IκB, IL-1and NF-κBin group PDTC was lower than those in group model. In addition, there wasno significant inhibition of PDTC on the expression of IL-6and TNF-β.（4）The expression of IFN-β in group model, group PTG and group PDTCin rat nasal tissues were slightly higher than that in control, but theexpression of IFN-β in group model, group PTG and group PDTC had nodifferences.（5）The expression of those cytokines mentioned above in group model,group PTG and group PDTC in human nasal epithelial cells HNEpC were higherthan those in control. And the expression of almost all of those cytokinesin group PTG were higher than those in group model and group PDTC exceptIFN-β. The expression of MyD88, IRAK-1, TRAF-6and TLR2in group PDTCwas nearly the same as group model, while the expression of IgE, IκB,IL-1and NF-κB in group PDTC was lower than those in group model. In addition, there was no significant inhibition of PDTC on the expressionof IL-6and TNF-β.（6）The expression of IFN-β in group model, group PTG and group PDTCin human nasal epithelial cells HNEpC were slightly higher than that incontrol, but the expression of IFN-β in group model, group PTG and groupPDTC had no differences.（7）TP relieved the nasal symptoms of rat with AR and decreased theexpression of all cytokines mentioned above.Conclusions:（1）The model of allergic rhinitis in rat can be established successfullyusing intraperitoneal injection and intranasal drop of OVA.（2）TLR2and NF-κB play a key role in TLR2-NF-κB signaling pathway.（3）We speculate that the pathogenesis of AR was as follow: after thenasal cells exposed to allergen, TLR2is activated, and firstly bindingwith MyD88, then IRAK-1is also activated, followed by activation ofNF-κB and IκB, and further to activate inflammatory cytokines such asIL-1, IL-6, TNF-β and IgE, thus induce allergic rhinitis.（4）The TLR2-NF-κB signaling pathway mediated by TLR2was a MyD88dependent pathway.（5）The pathogenesis of AR in rat and human have analogous mechanism andTLR2-NF-κB signaling pathway.（6）PDTC can significantly inhibit the expression of IL-1and IgE in ratnasal tissues and human nasal epithelial cells HNEpC, but not IL-6andTNF-β.（7）TP can effectively alleviate AR symptoms, which should be achievedby down-regulating the expression of those cytokines such as IL-1, IL-6,TNF-βand IgE. |
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