A recent Journal of Translational Medicine study indicates that interleukin (IL)-33 is produced by bronchial smooth muscle cells (BSMCs) upon rhinovirus (RV) infection and activation of TLR3, and that this response is associated and/or mediated by ATP released by viral-stimulated BSMCs.
IL-33 is a cytokine constitutively expressed in epithelial barrier tissues, and was originally described as a potent inducer of type 2 immune responses, activating T helper (Th) cells and mast cells, and implicated in allergic inflammation and asthma pathogenesis.
In the Journal of Translational Medicine study Jenny Calvén and colleagues from the Department of Experimental Medical Science, Lund University, Lund, Sweden report that IL-33 is produced upon RV infection and activation of TLR3 by double-stranded (ds)RNA of primary human BSMCs from healthy and asthmatic subjects. In this study extracellular ATP levels were increased rapidly after stimulation of BSMCs with dsRNA and elevated in supernatants from RV-infected BSMCs.
Importantly, ATP appear to mediate the release of IL-33 by BSMCs since ATP is produced upon RV infection and TLR3 activation, and the ATP secretion is blocked, in a concentration-dependent manner, by the broad inhibitor of purinergic signaling suramin.
The study of Calvén et al. suggests that rhinovirus (RV) infections contribute to an increased expression and production of IL-33 by BSMCs. In this process, the authors suggests that ATP, most likely epithelial-derived may promote and mediate the IL-33 expression, and the ATP/P2R-axis may play an important role in the viral stimuli-induced effects directly on BSMCs.