Abstract
BackgroundRoxithromycin (RXM) has been widely used in asthma treatment; however, the mechanism has not been fully understood. The aim of our study was to investigate the underlying mechanism of RXM treatment in mediating the effect of transforming growth factor (TGF)-β1 on airway smooth muscle cells (ASMCs) proliferation and caveolinn-1 expression.MethodsFirstly, the rat ovalbumin (OVA) model was built according to the previous papers. Rat ASMCs were prepared and cultured, and then TGF-β1 production in ASMCs was measured by enzyme-linked immunosorbent assay (ELISA). Moreover, the proliferation of ASMCs was determined using cell counting kit (CCK-8) assay. Additionally, the expressions of caveolin-1, phosphorylated-ERK1/2 (p-ERK1/2) and phosphorylated–AKT (p-AKT) in ASMCs treated with or without PD98059 (an ERK1/2 inhibitor), wortannin (a PI3K inhibitor), β-cyclodextrin (β-CD) and RXM were measured by Western blot. Finally, data were evaluated using t–test or one-way ANOVA, and then a P value < 0.05 was set as a threshold.ResultsCompared with normal control, TGF-β1 secretion was significantly increased in asthmatic ASMCs; meanwhile, TGF-β1 promoted ASMCs proliferation (P < 0.05). However, ASMCs proliferation was remarkably inhibited by RXM, β-CD, PD98059 and wortmannin (P < 0.05). Moreover, the expressions of p-ERK1/2 and p-AKT were increased and peaked at 20 min after TGF-β1 stimulation, and then suppressed by RXM. Further, caveolin-1 level was down-regulated by TGF-β1 and up-regulated by inhibitors and RXM.ConclusionOur findings demonstrate that RXM treatment inhibits TGF-β1-induced activation of ERK and AKT and down-regulation of caveolin-1, which may be the potential mechanism of RXM protection from chronic inflammatory diseases, including bronchial asthma.
Highlights
With inflammation being the principle underlying pathophysiological characteristic, asthma has been reported primarily as an inflammatory disorder, which would drive airway obstruction and remodeling [1]
transforming growth factor (TGF)-β1 production in airway smooth muscle cells (ASMCs) and the effect of transforming growth factor-β1 (TGF-β1) on ASMCs proliferation To determine the secretion of TGF-β1 in rat ASMCs, cells culture supernatants were collected and measured
TGF-β1 treatment was discovered significantly promoted the proliferation of ASMCs (P < 0.05, Figure 1B)
Summary
With inflammation being the principle underlying pathophysiological characteristic, asthma has been reported primarily as an inflammatory disorder, which would drive airway obstruction and remodeling [1]. Airway smooth muscle (ASM) has been discovered plays a central role in the pathogenesis of airway remodeling. Previous studies have showed that transforming growth factor-β1 (TGF-β1) is involved in the pathophysiology of asthma [3]. TGF-β1 has reported increases the secretion of marix metalloproteinase [5] and production of extracellular matrix [6] in ASMCs, suggesting a new mechanism of airway remodeling. The aim of our study was to investigate the underlying mechanism of RXM treatment in mediating the effect of transforming growth factor (TGF)-β1 on airway smooth muscle cells (ASMCs) proliferation and caveolinn-1 expression
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