{Reference Type}: Journal Article
{Title}: Lomerizine attenuates LPS-induced acute lung injury by inhibiting the macrophage activation through reducing Ca2+ influx.
{Author}: Song Y;Gou Y;Gao J;Chen D;Zhang H;Zhao W;Qian F;Xu A;Shen Y;
{Journal}: Front Pharmacol
{Volume}: 14
{Issue}: 0
{Year}: 2023
{Factor}: 5.988
{DOI}: 10.3389/fphar.2023.1236469
{Abstract}: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening lung diseases with high mortality rates, predominantly attributable to acute and severe pulmonary inflammation. Lomerizine (LMZ) is a calcium channel blocker previously used in preventing and treating migraine. Here, we found that LMZ inhibited inflammatory responses and lung pathological injury by reducing pulmonary edema, neutrophil infiltration and pro-inflammatory cytokine production in lipopolysaccharide (LPS)-induced ALI mice. In vitro experiments, upon treating with LMZ, the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was attenuated in macrophages. The phosphorylation of p38 MAPK, ERK1/2, JNK, and NF-κB p65 was inhibited after LMZ treatment. Furthermore, LPS-induced Ca2+ influx was reduced by treating with LMZ, which correlated with inhibition of pro-inflammatory cytokine production. And L-type Ca2+ channel agonist Bay K8644 (BK) could restore cytokine generation. In conclusion, our study demonstrated that LMZ alleviates LPS-induced ALI and is a potential agent for treating ALI/ARDS.