TNF and airway hyperresponsiveness: TNF-α is a prototype proinflammatory cytokine which has been proposed to exert deleterious effects directly on airway smooth muscle, including its most recently explored roles in (i) activation of transient receptor potential channel 3 (TRPC3) leading to abnormal store-operated calcium influx, and (ii) upregulation of CD38 which regulates intracellular calcium and plays a role in airway hyperresponsiveness [31], [32].