title: Cockroach allergen Per a 7 down-regulates expression of Toll-like receptor 9 and IL-12 release from P815 cells through PI3K and MAPK signaling pathways.
abstract: BACKGROUND
  As a major source of indoor allergens, cockroach causes perennial rhinitis and asthma. Recently, cockroach feces were reported to contain TLR2 agonist, which could directly activate neutrophils to release cytokines. CpG oligodeoxynucleotide (ODN), a Toll-like receptor (TLR)9 activator was also found to induce proinflammatory cytokine release from mast cells. However, influence of specific cockroach allergen on Th1 cytokine release and expression of TLR9 in mast cells remains uninvestigated.
  
  
  METHODS
  To investigate effects of Per a 7 on TLR expression and cytokine release from mast cells and their cell signaling mechanisms, P815 cells were challenged by recombinant Per a 7 (rPer a 7), and expression of TLR9 mRNA and protein was assessed mainly by real time PCR and flow cytometry analysis. Detection of phosphorylation of cell signaling components was performed with Western blotting technique.
  
  
  RESULTS
  The results showed that rPer a 7 induced up to 72 and 46% down-regulation of expression of TLR9 mRNA and protein, respectively following 16 h incubation period. It induced also approximately 41.1% reduction of IL-12 release. When PD98059, U0126 and LY294002 were pre-incubated with the cells for 30 min they diminished rPer a 7 induced reduction of TLR9 expression and IL-12 release, indicating these events are via activation of ERK and PI3K/Akt signaling pathways.
  
  
  CONCLUSIONS
  Reduction of IL-12 production and expression of TLR9 in P815 mastocytoma cells by Per a 7 suggests that this major cockroach allergen might contribute to the development of cockroach allergy.
authors.affiliation: Clinical Research Centre, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Yang
authors.forename: Xue
authors.initials: X
authors.lastname: Kong
authors.forename: Jifu
authors.initials: J
authors.lastname: Wei
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Liu
authors.forename: Weijuan
authors.initials: W
authors.lastname: Song
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Shaoheng
authors.initials: S
authors.lastname: He
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D003058:Cockroaches / Q000276:immunology; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D007093:Imidazoles / Q000494:pharmacology; D019476:Insect Proteins / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology*; D020935:MAP Kinase Signaling System; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013997:Time Factors; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000485:Allergens; D002070:Butadienes; D002867:Chromones; D005419:Flavonoids; D007093:Imidazoles; D019476:Insect Proteins; D009025:Morpholines; D009570:Nitriles; D011725:Pyridines; D012333:RNA, Messenger; D011994:Recombinant Proteins; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; C113580:U 0126; C118755:allergen Per a 7, Periplaneta americana; D018664:Interleukin-12; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one