Calcium-sensing receptor antagonists, calcilytics, prevent activation of human dendritic and epithelial cells by urban particulate matter

Introduction: Previously we have shown that blockers of the calcium-sensing receptor (CaSR, calcilytics), reduce BHR, inflammation and remodelling in Th2/IgE- and alarmin-driven asthma models. Exposure to urban particulate matter (UPM) exacerbates asthma symptoms. It is unclear whether UPM exerts its effects via the CaSR. Aim: To determine which airway cells express the CaSR and whether UPM exerts its effects by acting directly at the CaSR. Methods: Immunohistochemistry (expression of CaSR immunoreactivity); intracellular calcium sensing (CaSR activity); flow cytometry (cellular maturation and cytokine production); qPCR (TSLP mRNA expression). Results: CaSR immunoreactivity was detected on human monocytes, myeloid dendritic cells, immature and mature monocyte-derived dendritic cells (MDDC), neutrophils, alveolar macrophages and bronchial epithelial cells (HBEC). UPM mobilised intracellular calcium in HEK-293 cells stably transfected with the human CaSR but not empty vector, an effect inhibited by calcilytics (p Conclusions: The CaSR is present in inflammatory and epithelial cells involved in asthma pathogenesis. UPM acts on the CaSR on MDDC and airway epithelial cells to induce inflammatory cytokines including alarmins, an effect likely relevant to asthma exacerbation and inhibitable by calcilytics.