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.

The emerging role of transient receptor potential channels in chronic lung disease

“…In the lung, TRPV1 expression has been found in human bronchial epithelial cells with an increase in expression in cells from the airways of patients with refractory asthma [99][100][101][102][103][104][105]109], fibroblasts [102], T-cells [106,107,115] and human alveolar macrophages [99]. Several studies suggest that TRPV1 channel activation evokes the release of proinflammatory cytokines and ATP from bronchial epithelial cells [99,[103][104][105]116].…”

“…Given the emergence of potent TRPV1 inhibitors with appropriate pharmacokinetic profiles for in vivo studies the picture should become clearer in the future [11]. In the absence of definitive preclinical data, there are data available from human in vitro studies where increased TRPV1 gene expression has been demonstrated in asthma [100,102], and population-based genetic association studies which have documented a TRPV1 genetic variant to be associated with a lower risk of childhood asthma or the presence of wheezing [123].…”

Structural Determinants of the Transient Receptor Potential 1 (TRPV1) Channel Activation by Phospholipid Analogs

“…The transient receptor potential vanilloid 1 (TRPV1) 3 is a member of the TRP channel family of ion channels that has been widely associated with painful processes such as angina pectoris, arthritis, and cancer, as well as inflammatory events (1)(2)(3)(4)(5). The activation of this receptor in the peripheral sensory cells where it is expressed leads to pain perception (6,7).…”

“…LPA has been importantly linked to neuropathic pain, and for several years it was thought to produce it solely through its interaction with specific GPCRs (LPA [1][2][3][4][5][6] ) (12,13), with the LPA 1 receptor being particularly important in this process (14). Recently, our group demonstrated a direct and physiologically relevant interaction of TRPV1 with LPA.…”

Chronic cough hypersensitivity syndrome

“…Есть мнение, что у лиц с ХК увеличивается количество рецепторов TRPV1 в подслизистом слое ДП [10]. Кроме того, функ ция этих рецепторов стимулируется воспалитель ными медиаторами [11]. В экспериментальных исследованиях in vitro показано, что риновирус поражает нейроны человека и активирует TRPV1 и TRPA1 рецепторы [8].…”