Bk channels regulate LPS-induced CCL-2 release from human pulmonary endothelial cells

Tatiana Zyrianova, Benjamin Lopez, Andy Liao, Charles Gu, Leanne Wong, Michela Ottolia, Riccardo Olcese, Andreas Schwingshackl

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


We recently established a role for the stretch-activated two-pore-domain K1 (K2P) channel TREK-1 (K2P2.1) in inflammatory cytokine secretion using models of hyperoxia-, mechanical stretch-, and TNF-a-induced acute lung injury. We have now discovered the expression of large conductance, Ca21-activated K1 (BK) channels in human pulmonary microvascular endothelial cells and primary human alveolar epithelial cells using semiquantitative real-time PCR, IP and Western blot, and investigated their role in inflammatory cytokine secretion using an LPS-induced acute lung injury model. As expected, LPS induced IL-6 and CCL-2 secretion from pulmonary endothelial and epithelial cells. BK activation with NS1619 decreased LPS-induced CCL-2 but not IL-6 secretion from endothelial cells and had no effect on epithelial cells, although fluorometric assays revealed that BK activation hyperpolarized the plasma membrane potential (Em) of both cell types. Interestingly, BK inhibition (Paxilline) did not alter cytokine secretion or the Em in either cell type. Furthermore, LPS treatment by itself did not affect the Em or intracellular Ca21 concentrations. Therefore, we propose BK channel activation as a novel targeted approach to counteract LPS-induced CCL-2 secretion from endothelial cells. This protective effect appears to occur via Em hyperpolarization but independent of intracellular Ca21 concentrations.

Original languageEnglish
Pages (from-to)224-234
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number2
StatePublished - 2021


  • Acute lung injury
  • Cytokines
  • Inflammation
  • LPS
  • Large conductance potassium channels


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