The supplementation of zinc increased the apoptosis of airway smooth muscle cells by increasing p38 phosphorylation

Proliferation of airway smooth muscle cells (ASMCs) is believed to play an important role in causing airway hyperresponsiveness (AHR). It has also been reported that platelet-derived growth factor (PDGF) can stimulate proliferation of ASMCs. We hypothesize that the concentration of zinc in the bodies of asthmatic patients may play a role in PDGF activity and therefore may be related to the variations in severity of airway inflammation and narrowing seen in asthmatic patients. We investigated the effects and mechanisms of zinc supplementation in PDGF-treated ASMCs.In this study, PDGF-treated primary ASMCs were cultured with 3, 12, 24, or 96 μM ZnSO4. We found that the highest concentration of ZnSO4 (96 μM) was cytotoxic for ASMCs. PDGF was used to induce ASMCs proliferation under different zinc concentrations. Neither 3 μM nor 12 μM ZnSO4 inhibited proliferation of PDGF-treated ASMCs, although 24 μM ZnSO4 caused treatment-induced apoptosis in PDGF-treated ASMCs. Supplementation with 24 μM ZnSO4 may therefore increase p38 activation and reduce Akt phosphorylation. Zinc supplementation may reduce proliferation of PDGF-treated ASMCs through the activation of p38 mitogen-activated protein kinase (MAP kinase) and suppression of Akt phosphorylation, which both drive the induction of cellular apoptosis, subsequently reducing the proliferation of ASMCs.

► Proliferation of ASMCs is an important role in causing airway hyperresponsiveness.
► Asthmatic patients suffer from airway inflammation and narrowing, which may be related to the zinc.
► Supplementation with Zn is thought to reduce AHR and airway inflammation.
► Zn reduced the proliferation of PDGF-treated ASMCs through p38 and Akt phosphorylation.