title: TLR3 and TLR7 modulate IgE production in antigen induced pulmonary inflammation via influencing IL-4 expression in immune organs.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  E3 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 IgG(1) 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.
  
  
  CONCLUSIONS
  TLR3 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.
authors.affiliation: Department of Genetics and Molecular Biology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Liesu
authors.initials: L
authors.lastname: Meng
authors.forename: Xiaojing
authors.initials: X
authors.lastname: He
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zhu
authors.forename: Xudong
authors.initials: X
authors.lastname: Yang
authors.forename: Congshan
authors.initials: C
authors.lastname: Jiang
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Sun
authors.lastname: M B
authors.forename: Simeng
authors.initials: S
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Xue
authors.forename: Xinfang
authors.initials: X
authors.lastname: Xie
authors.forename: Shemin
authors.initials: S
authors.lastname: Lu
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000235:genetics; D000941:Antigens; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D007107:Immune System / Q000276:immunology / Q000378:metabolism*; D007154:Immune System Diseases / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D000941:Antigens; D012333:RNA, Messenger; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin