Antigen‐induced airway hyperresponsiveness and obstruction is related to caveolin‐1 expression in airway smooth muscle in a guinea pig asthma model

Abstract

BackgroundCaveolin-1 is a fundamental signalling scaffold protein involved in contraction; however, the role of caveolin-1 in airway responsiveness remains unclear. We evaluated the relationship between caveolin-1 expression in airway smooth muscle (ASM) and antigen-induced airway responsiveness and obstruction in a guinea pig asthma model.MethodsAirway obstruction in sensitised guinea pigs, induced by antigenic (ovalbumin) challenges administered every 10 days, was measured. Antigen-induced responsiveness to histamine and the expression of caveolin-1 and cavin 1, 2 and 3 were evaluated at the third ovalbumin challenge. The control group received saline solution instead of ovalbumin.ResultsAfter the first challenge, antigen exposure induced a transient airway obstruction and airway hyperresponsiveness, high levels of IL-4 and IL-5 in lung and airway globet cells proliferation at the third antigenic challenge. Caveolin-1 mRNA levels in total lung decreased in the experimental group compared with controls. Flow cytometric analysis of ASM from the experimental group showed a high number of cells expressing caveolin-1 compared with controls. This increase was confirmed by western blot. Airway obstruction and hyperresponsiveness correlated with the degree of increased caveolin-1 expression in ASM cells (P < 0.05; r = 0.69 and −0.52, respectively). The expression of cavins 1, 2 and 3 in ASM also increased in the experimental group compared to controls. Immunohistochemical findings reveal that differences in ASM caveolin-1 were not evident between groups. Nevertheless, a marked decrease in caveolin-1 and caspase 3 was observed in the pulmonary vascular smooth muscle of asthma model compared with controls. Histological analysis did not reveal differences in smooth muscles mass or subepithelial fibrosis levels in airways between groups. However, an enlargement of smooth muscle mass was observed in the pulmonary microvessels of experimental animals. This enlargement did not induce changes in pulmonary or systemic arterial pressures.ConclusionsOur data suggest that caveolin-1 expression in ASM has a crucial role in the development of antigen-induced airway obstruction and hyperresponsiveness in a guinea pig asthma model. In addition, the asthma model in guinea pigs appears to induce a contractile smooth muscle phenotype in the airways and a proliferative smooth muscle phenotype in pulmonary vessels.

PTRF-IL33-ZBP1 signaling mediating macrophage necroptosis contributes to HDM-induced airway inflammation

“…The lungs express numerous caveolae and high levels of PTRF, which play important roles in pulmonary diseases such as lung cancer and pulmonary hypertension [ 6 , 17 ]. Expression of PTRF in the airway smooth muscle is increased in an OVA-induced asthma model [ 18 ]. Partial loss of PTRF led to a greater AHR and potent type 2 immune responses during challenge phase of OVA-induced asthma model, without influencing the sensitization phase.…”

Overexpression of programmed cell death 5 in a mouse model of ovalbumin-induced allergic asthma

“…The level of apoptotic caspase-3 protein was found increased in bronchial epithelial cells or lung tissues in asthma [10–12]. In contrast, its level was markedly decreased in pulmonary vascular smooth muscle of an asthma model [13]. Apoptosis is also a central and essential process in the resolution of inflammation.…”

Airway Hyperresponsiveness in Asthma Model Occurs Independently of Secretion of β1 Integrins in Airway Wall and Focal Adhesions Proteins Down Regulation

“…Animal models of asthma are helpful in the understanding of the disease. Previous studies from our laboratory have shown that the guinea pig allergic asthma model generates airway obstruction and hyperresponsiveness, high ovalbumin‐IgE and ‐IgG1 levels, granulocyte infiltration, increased lung levels of TNF‐α, IL‐4, and IL‐5, remodeling features of asthma such as goblet cell and vascular smooth muscle hyperplasia, and accumulation and alteration of extracellular matrix components [Bazan‐Perkins et al, ; Moreno‐Alvarez et al, ; Ramos‐Ramirez et al, ; Alvarez‐Santos et al, ].…”