In the pathogenesis of asthma, the proliferation of airway smooth muscle cells (ASMCs) is a key factor in airway remodeling and causes airway narrowing. In addition, ASMCs are also the effector cells of airway inflammation. Fucoidan extracted from marine brown algae polysaccharides has antiviral, antioxidant, antimicrobial, anticlotting, and anticancer properties; however, its effectiveness for asthma has not been elucidated thus far. Platelet-derived growth factor (PDGF)-treated primary ASMCs were cultured with or without oligo-fucoidan (100, 500, or 1000 µg/mL) to evaluate its effects on cell proliferation, cell cycle, apoptosis, and Akt, ERK1/2 signaling pathway. We found that PDGF (40 ng/mL) increased the proliferation of ASMCs by 2.5-fold after 48 h (p < 0.05). Oligo-fucoidan reduced the proliferation of PDGF-stimulated ASMCs by 75%–99% after 48 h (p < 0.05) and induced G1/G0 cell cycle arrest, but did not induce apoptosis. Further, oligo-fucoidan supplementation reduced PDGF-stimulated extracellular signal-regulated kinase (ERK1/2), Akt, and nuclear factor (NF)-κB phosphorylation. Taken together, oligo-fucoidan supplementation might reduce proliferation of PDGF-treated ASMCs through the suppression of ERK1/2 and Akt phosphorylation and NF-κB activation. The results provide basis for future animal experiments and human trials.
The vagal nerve trunk in the mediastinum of mammals divides into two main branches, the thoracic vagus nerve and the recurrent laryngeal nerve, in which the sensory nerve axons are largely involved in neurogenic inflammation in the tracheobronchial airways. A previous study demonstrated that cutting the right-side thoracic vagus nerve but not the recurrent laryngeal nerve inhibited capsaicin-induced neurogenic inflammation in the right bronchial tree of the rat. The effect of left thoracic vagus nerve section is still not known. The main purpose of the present study was to investigate the effect of sectioning the right or left thoracic vagus nerve on the innervation density of substance P-immunoreactive axons in bilateral bronchial trees. Following nerve degeneration, the whole mounts of airway tissues were processed with substance P immunohistochemistry. Denervation of either thoracic vagus nerve reduced the innervation density of axons by 38-71% in different parts of the ipsilateral bronchial tree. The effect of right recurrent laryngeal nerve section was less specific; the innervation density was reduced by 21-39% in the trachea and bronchi of both sides. Capsaicin-induced neurogenic plasma leakage was decreased in the left mainstem bronchus and lobar bronchi after left thoracic vagus nerve section. It is concluded that the thoracic vagus nerve largely contributed to the sensory innervation in the ipsilateral bronchial airways and modulated their functions.
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