Calcium signaling and β2-adrenergic receptors regulate 1-nitropyrene induced CXCL8 responses in BEAS-2B cells.

Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are widespread environmental pollutants, generated from reactions between PAHs and nitrogen oxides during combustion processes. In the present study we have investigated the mechanisms of CXCL8 (IL-8) responses induced by 1-nitropyrene (1-NP) in human bronchial epithelial BEAS-2B cells, with focus on the possible importance of Ca(2+)-signaling and activation of β2-adrenergic receptors (β2AR). Ca(2+)-chelator treatment obliterated 1-NP-induced CXCL8 (IL-8) responses. 1-NP at 10μM (but not 1μM) induced a rapid and sustained increase in intracellular Ca(2+)-levels ([Ca(2+)]i). The early but not the later, sustained phase of 1-NP-induced [Ca(2+)]i was suppressed by beta-blocker treatment (carazolol). Moreover, inhibition of β2AR by blocking-antibody, beta-blocker treatment (ICI 118551) or siRNA transfection attenuated CXCL8 responses induced by 1-NP. The results confirm that PAHs may induce Ca(2+)-signaling also in BEAS-2B cells, at least partly through activation of β2AR, and suggest that both β2AR- and Ca(2+)-signaling may be involved in 1-NP-induced CXCL8 responses in bronchial epithelial cells.