Abstract
BackgroundToll-like receptors (TLRs) as pattern recognition receptors, participate in both innate and adaptive immune responses, and seem to play an important role in the pathogenesis of asthma. This study aimed to identify key TLRs involved in antigen induced pulmonary inflammation (AIPI), a rat model for asthma, and to explore the role of TLRs in the disease development.Methods and FindingsE3 rats were sensitized with ovalbumin (OVA)/alum intraperitoneally and intranasally challenged with OVA to induce AIPI model. TLR1-9 and cytokine mRNA expression in spleen, lung and mediastinal lymph node (mLN) tissues were screened by quantitative real-time polymerase chain reaction. TLR7 expression was found to be significantly down-regulated in spleen while TLR3 and TLR8 expression was up-regulated in mLN of AIPI rats. Furthermore, imiquimod (a ligand of TLR7) and TLR3 specific short-hairpin RNA plasmid for RNA interference were administrated, respectively, in vivo to AIPI rats to observe their effects on the disease by assessing various asthmatic parameters. The numbers of total cells, eosinophils, macrophages and lymphocytes were counted according to differential morphology in bronchoalveolar lavage fluid. Serum IgE and OVA specific IgG1 concentration was detected by enzyme-linked immunosorbent assay. The results showed that both TLR7 ligand treatment and TLR3 RNAi in vivo decreased serum IgE level and interleukin-4 mRNA expression.Conclusion/SignificanceTLR3 in mLN and TLR7 in spleen both systemically modulate disease development in AIPI rats via altering serum IgE concentration relevant to Th2 responses. And these findings may provide an important clue for further research in the asthma pathogenesis and suggest a new remedy for asthma treatment.
Highlights
Asthma with a high mobidity is an inflammatory disease of the lower airways
TLR3, TLR7 and TLR8 mRNA expression was regulated in immune organs of E3 rats in antigen induced pulmonary inflammation (AIPI) model
TLR7 transcripts in spleen tissues from AIPI rats were significantly reduced compared with control rats, and no significant difference in other Toll-like receptors (TLRs) mRNA expression levels was detected (Figure 1A)
Summary
It is widely accepted that Th2 cells are critical regulators of asthma pathogenesis [1,2]. Th2 cells secrete inflammatory cytokines, such as interleukin-4 (IL-4), and interleukin-5, which play key roles in the development of asthma [3]. TLRs, which play a crucial role in both innate and adaptive immune response, can recognize pathogen-associated molecular patterns and their activation can induce the production of proinflammatory cytokines [4]. Toll-like receptors (TLRs) as pattern recognition receptors, participate in both innate and adaptive immune responses, and seem to play an important role in the pathogenesis of asthma. This study aimed to identify key TLRs involved in antigen induced pulmonary inflammation (AIPI), a rat model for asthma, and to explore the role of TLRs in the disease development
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