Negative feedback of NF-κB signaling by long noncoding RNA MALAT1 controls lipopolysaccharide-induced inflammation injury in human lung fibroblasts WI-38.

Abstract

The study was designed to elucidate the regulatory mechanism of long noncoding RNA human metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in lipopolysaccharides (LPS)-caused inflammation injury in human lung fibroblasts WI-38. WI-38 cells were stimulated with LPS to construct acute pneumonia cell model. MALAT1 in LPS-stimulated WI-38 cells was examined. LPS-induced inflammation injury was estimated using viability, apoptosis, and cytokine secretion including interleukin-1β (IL-1β) and IL-6. Furthermore, the modulatory relations of MALAT1 and nuclear factor-kappa B (NF-κB) signaling were explored. We found that the sensitivity of WI-38 cells to apoptosis was enhanced by LPS-caused inflammation. Moreover, LPS promoted MALAT1 expression which was found to alleviate LPS-caused damages. Besides, NF-κB p65 overexpression resulted in an increased expression of MALAT1, and MALAT1 was identified as a target gene of p65. Furthermore, overexpression of MALAT1 reduced NF-κB activation. Pulldown assay showed that MALAT1 could directly interact with p65. Taken together, our findings revealed that MALAT1 was upregulated in LPS-stimulated WI-38 cells. Through directly interacting with p65, MALAT1 blocked LPS-caused activation of NF-κB and repressed LPS-induced inflammation injury. MALAT1 may serve as a potential diagnostic indicator or therapeutic target for pneumonia.