title: Study on TRPV1-mediated mechanism for the hypersecretion of mucus in respiratory inflammation.
abstract: Transient receptor potential vanilloid 1 (TRPV1) is sensitized by the high affinity TrkA receptor, which promotes pro-inflammatory cytokine production and mediates mucus hypersecretion in bronchial epithelial cells. The purpose of this study was to investigate the mechanism of TRPV1-mediated mucus hypersecretion and respiratory inflammation. Firstly, using Western blot analysis we found that epidermal growth factor receptor (EGFR) and TRPV1 were highly co-expressed in human bronchial epithelial cells (HBE16) with HNE and capsaicin co-treated, the levels of pro-inflammatory cytokines and MUC5AC were also highly co-expressed; however, TRPV1 receptor expression was low in these cells with only HNE stimulation, which demonstrated that sensitization of TRPV1 was not increased in HBE16 cells treated with HNE alone. Secondly, the EGF receptor antagonist (AG1478) and the TrkA receptor inhibitor (K252a) significantly inhibited TRPV1 sensitivity and the expression of MUC5AC and pro-inflammatory cytokines. Furthermore, the PI3K inhibitor LY294002, the PKC inhibitor bisindoylmaleimide (BIM) and the TRPV1 antagonist capsazepine completely abrogated the EGF sensitizing effect. Furthermore, the hypoxia-inducible factor (HIF-1α) inhibitor 2-methoxyestradiol (2-ME2) decreased the activity of PKC by a specific pathway. These findings strongly suggest that TRPV1 sensitization influences the hypersecretion of mucus and inflammatory cytokines, is associated with the PI3K and PKC signaling pathways and is involved HIF-1α activity.
authors.affiliation: Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China; Division of Respiratory Medicine, Banan District People's Hospital, Chongqing 401320, China.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: H M
authors.initials: HM
authors.lastname: Yu
authors.forename: X D
authors.initials: XD
authors.lastname: Zhou
authors.forename: V P
authors.initials: VP
authors.lastname: Kolosov
authors.forename: J M
authors.initials: JM
authors.lastname: Perelman
mesh_terms: D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009093:Mucus / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011014:Pneumonia / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D050916:TRPV Cation Channels / Q000378:metabolism*; D014162:Transfection
chemical_list: D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors