The Study Of TLR2-STAT3 Pathway In The Pathogenesis Of Allergic Inflammation

Objective: To explore the role of TLR2-STAT3 pathway in the pathogenesis of allergic inflammation by observing the changes of STAT3 expression in lung tissue and inflammatory markers between the TLR2-/- OVA mice and C57Bl/6 OVA mice.Methods:1. The C57Bl/6 OVA and TLR2-/- OVA mice were injected with OVA and Al(OH)3 on days 0 and 7 to establish the sensitization model. The C57Bl/6 NS and TLR2-/- NS mice were treated with saline to establish the control model, five mice per group.2. Hematoxylin-eosin staining was used to observe the lung tissue inflammatory cell infiltration and microscope was used to observe the inflammatory cell count in BALF.3. The expression levels of IL-4, IL-5 and IL-13 mRNA were measured by RT-PCR.4. The concentrations of mouse OVA-IgE, IgA, IgM, IgG1, IgG2 a and IgG2 b in serum were detected by ELISA.5. Immunofluorescence/ Immunohistochemistry was used to observed the STAT3/ NF-κB protein in the lung tissue.6. The C57Bl/6 mice were administered with CPT at does of 200mg/kg/d before each sensitization. The expressions of STAT3 and NF-κB, the concentration of IgG1 and mouse lung structural changes were then observed.Results:1. The sensitized model was successfully established by intraperitoneal injection of OVA and Al(OH)3. Compared with C57Bl/6 NS mice, the C57Bl/6 OVA mice showed worse inflammatory cell infiltration around the bronchioles, the higher expressions of IL-4 and IL-13 mRNA and the higher concentrations of IgG1、IgA、IgG2a、IgG2b、IgM and IgE in serum(p?0.05).2. The inflammatory cell infiltration around the bronchioles in lung tissue was reduced, the expressions of IL-4 mRNA and IL-13 mRNA were both down-regulated, the mouse OVA-IgE concentration was increased but IgG1 was decreased, and STAT3 protein expression was down-regulated in TLR2 knockout mice after sensitized with OVA compared with C57Bl/6 OVA mice, all of the above differences were statistically significant(p?0.05), but NF-κB had no change.3. CPT reduced the expression of STAT3, the mouse OVA-IgG1 concentration and the inflammatory cell infiltration around the bronchioles, but had no effect on NF-κB expression.Conclusions:1. TLR2 can increase IgG1 concentration via STAT3, to promote Th2 type inflammatory response caused by OVA.2. CPT can downregulate IgG1 concentration by the inhibition of TLR2-STAT3 pathway and can improve the inflammatory cell infiltration in lung tissue.