title: Inflammatory stimuli up-regulate transient receptor potential vanilloid-1 expression in human bronchial fibroblasts.
abstract: Lung fibroblasts are involved in interstitial lung disease, chronic asthma, and chronic obstructive pulmonary disease (COPD). The expanded fibroblast population in airway disease leads to airway remodeling and contributes to the inflammatory process seen in these diseases. The cation channel transient receptor potential vanilloid-1 (TRPV1) is activated by noxious stimuli, including capsaicin, protons, and high temperatures and is thought to have a role in inflammation. Although TRPV1 expression is primarily reported to be neuronal, some extraneuronal expression has been reported. The authors therefore sought to determine whether human primary bronchial fibroblasts (HPBFs) express TRPV1 and whether inflammatory mediators can induce TRPV1 expression. The authors show that fibroblasts are predominantly TRPV1 negative; however, following stimulation with 3 common inflammatory mediators, tumor necrosis factor α (TNF-α), lipopolysaccharide (LPS), and interleukin-1α (IL-1α), TRPV1 mRNA was observed at 24 and 48 hours post treatment with all 3 mediators. Using Western blotting an increase in TRPV1 expression with all 3 inflammatory mediators was detected with significant increases seen at 72 hours post LPS and IL-1α treatment. In stark contrast to the untreated fibroblasts, significant calcium signaling in response to capsaicin and resiniferatoxin in HPBFs treated for 24 and 48 hours with TNF-α, LPS, or IL-1α was also observed. These results indicate that TRPV1 can be expressed on bronchial fibroblasts in situations where an underlying inflammatory stimulus exists, as is the case in airway diseases such as asthma and COPD.
authors.affiliation: Cardiovascular and Respiratory Studies, University of Hull, Castle Hill Hospital, Cottingham, East Yorkshire, UK. L.R.Sadofsky@Hull.ac.uk
authors.forename: Laura R
authors.initials: LR
authors.lastname: Sadofsky
authors.forename: Rithwik
authors.initials: R
authors.lastname: Ramachandran
authors.forename: Christopher
authors.initials: C
authors.lastname: Crow
authors.forename: Michael
authors.initials: M
authors.lastname: Cowen
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Compton
authors.forename: Alyn H
authors.initials: AH
authors.lastname: Morice
mesh_terms: D056151:Airway Remodeling; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020013:Calcium Signaling / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D053582:Interleukin-1alpha / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004224:Diterpenes; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D008070:Lipopolysaccharides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D014409:Tumor Necrosis Factor-alpha; C024353:resiniferatoxin; D002211:Capsaicin