Abstract
Acute lung injury (ALI) is a significant cause of morbidity and mortality worldwide. To search for a new treatment for acute lung injury, we investigated the effect of escitalopram on lipopolysaccharide (LPS)-induced ALI. Our results showed that escitalopram inhibited salt-inducible kinase 2 (SIK2) activity (IC50 = 6.36 ± 0.93 μM) and triggered histone deacetylase 4 (HDAC4) dephosphorylation. Following its dephosphorylation, HDAC4 translocated into the nucleus, promoted deacetylation and cytoplasmic shuttling of p65, thus inhibited LPS-induced pro-inflammatory cytokine production. Moreover, escitalopram markedly ameliorated the inflammatory responses, reduced neutrophils infiltration and attenuated LPS-induced pulmonary injury in mice. Taken together, we identified a previously unexplored role for escitalopram in SIK2/HDAC4/NF-κB pathway, therefore escitalopram may be considered as a new treatment for ALI.
【초록키워드】 Treatment, Inflammatory responses, neutrophil, Lung injury, acute lung injury, IC50, mice, pathway, morbidity and mortality, pulmonary injury, infiltration, pro-inflammatory cytokine, nucleus, investigated, inhibited, reduced, cytoplasmic, triggered, ameliorated, promoted, p65, HDAC4, SIK2, translocated, 【제목키워드】 drug, acute lung injury, escitalopram, cascade, NF-κB signaling, inhibiting, attenuate,