Unfolded protein response suppression potentiates LPS-induced barrier dysfunction and inflammation in bovine pulmonary artery endothelial cells

ABSTRACT

The development of novel strategies to counteract diseases related to barrier dysfunction is a priority, since sepsis and acute respiratory distress syndrome are still associated with high mortality rates. In the present study, we focus on the effects of the unfolded protein response suppressor (UPR) 4-Phenylbutyrate (4-PBA) in Lipopolysaccharides (LPS)-induced endothelial injury, to investigate the effects of that compound in the corresponding damage. 4-PBA suppressed binding immunoglobulin protein (BiP) – a UPR activation marker – and potentiated LPS – induced signal transducer and activator of transcription 3 (STAT3) and extracellular signal‑regulated protein kinase (ERK) 1/2 activation. In addition to those effects, 4-PBA enhanced paracellular hyperpermeability in inflamed bovine pulmonary endothelial cells, and did not affect cell viability in moderate concentrations. Our observations suggest that UPR suppression due to 4-PBA augments LPS-induced endothelial injury, as well as the corresponding barrier disruption.

KEYWORDS:

• barrier function
• endoplasmic reticulum
• unfolded protein response

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Our work is supported by the Institutional Development Award (IDeA) from NIGMS/NIH (3P20GM103424-21).