Inactivation of capsaicin-sensitive nerves reduces pulmonary remodeling in guinea pigs with chronic allergic pulmonary inflammation

Abstract

Pulmonary remodeling is an important feature of asthma physiopathology that can contribute to irreversible changes in lung function. Although neurokinins influence lung inflammation, their exact role in the extracellular matrix (ECM) remodeling remains to be determined. Our objective was to investigate whether inactivation of capsaicin-sensitive nerves modulates pulmonary ECM remodeling in animals with chronic lung inflammation. After 14 days of capsaicin (50 mg/kg, sc) or vehicle administration, male Hartley guinea pigs weighing 250-300 g were submitted to seven inhalations of increasing doses of ovalbumin (1, 2.5, and 5 mg/mL) or saline for 4 weeks. Seventy-two hours after the seventh inhalation, animals were anesthetized and mechanically ventilated and the lung mechanics and collagen and elastic fiber content in the airways, vessels and lung parenchyma were evaluated. Ovalbumin-exposed animals presented increasing collagen and elastic fiber content, respectively, in the airways (9.2 ± 0.9; 13.8 ± 1.2), vessels (19.8 ± 0.8; 13.4 ± 0.5) and lung parenchyma (18.8 ± 1.1; 25.31 ± 1.1) compared to control (P < 0.05). Capsaicin treatment reduced collagen and elastic fibers, respectively, in airways (1.7 ± 1.1; 7.9 ± 1.5), vessels (2.8 ± 1.1; 4.4 ± 1.1) and lung tissue (12.46 ± 1.0; 15.05 ± 1.5) of ovalbumin-exposed animals (P < 0.05). These findings were positively correlated with lung mechanical responses to antigenic challenge (P < 0.05). In conclusion, inactivation of capsaicin-sensitive nerve fibers reduces pulmonary remodeling, particularly collagen and elastic fibers, which contributes to the attenuation of pulmonary functional parameters.

Vagal‐α7nAChR signaling attenuates allergic asthma responses and facilitates asthma tolerance by regulating inflammatory group 2 innate lymphoid cells

“…PCFs are capsaicin‐sensitive nerves, and recent studies have revealed that degeneration of PCFs by capsaicin pretreatment but not downstream receptor TRPV1 (transient potential receptor vanilloid 1) blockade can decrease allergic airway inflammatory responses, including eosinophils, Th2 cells and inflammatory cytokines, as well as reduce asthmatic hyperreactivity and airway remodeling in an asthma model 30,32,33,40,41 . However, whether PCFs have effects on ILC2s, especially iILC2s, in asthma and tolerance is not very clear.…”

“…Previous studies have shown that vagotomy, PCF degeneration or α7nAChR activation can alleviate allergen‐induced airway hyperreactivity and reduce allergic airway inflammation in asthma models, including eosinophils and Th2 cells infiltration and inflammatory cytokines production 14,30,32,33,35,36,40,41 . Consequently, our research has a minor flaw in that we mainly focused on changes in ILC2 numbers.…”

PACS2–TRPV1 axis is required for ER–mitochondrial tethering during ER stress and lung fibrosis

“…It has been reported to show inhibitory effects in hepatic fibrosis [ 36 ] and to prevent renal damage in acute kidney injury [ 42 ]. In the lung, CPS has been shown to reduce pulmonary remodeling and collagen fibrils in vessels and lung tissues of animals with chronic lung inflammation [ 32 ]. Further, one study showed that low doses of CPS alleviated bleomycin-induced lung fibrosis via inhibiting ERK1/2/eIF3a signaling in the alveolar epithelial cells [ 22 ].…”

Roles of Bronchopulmonary C-fibers in airway Hyperresponsiveness and airway remodeling induced by house dust mite

“…To probe the mechanisms underlying the PCFs’ contribution to the HDM-induced AHR, we detected the level of pulmonary SP. The latter is primarily synthesized in the cell bodies of PCFs [ 11 ] and released locally from peripheral sensory terminals upon stimulation [ 24 ]. It is responsible for airway/lung neurogenic inflammation, promotes ASM contraction, AHR, mucus hypersecretion and inflammation in asthma [ 13 , 14 , 16 ].…”

“…PCFs have been reported to participate in the allergic airway inflammation, the ovalbumin-induced pulmonary remodeling, and the RSV-induced AHR. Previous studies showed that PCF degeneration by neonatal capsaicin (CAP) pretreatment decreased the allergic airway inflammation [ 10 ] and the pulmonary remodeling characterized by collagen and elastic fiber deposition in airways [ 11 ] in ovalbumin-induced asthma model. PCF degeneration also eliminated the AHR induced by respiratory syncytial viral infection [ 12 ].…”