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

Toxicol In Vitro. 2014 Sep;28(6):1153-7. doi: 10.1016/j.tiv.2014.05.012. Epub 2014 Jun 4.

Abstract

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.

Keywords: Adrenergic receptors; Calcium; Chemokines; Inflammation; Lung; Polycyclic aromatic hydrocarbons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Calcium Signaling / drug effects*
  • Cell Line
  • Gene Expression / drug effects
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Pyrenes / toxicity*
  • RNA, Small Interfering / administration & dosage
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-2 / metabolism*

Substances

  • CXCL8 protein, human
  • Interleukin-8
  • Pyrenes
  • RNA, Small Interfering
  • Receptors, Adrenergic, beta-2
  • Calcium
  • 1-nitropyrene