circAtp9b knockdown alleviates LPS-caused inflammation provided that microRNA-27a is upregulated

Abstract

Background: The etiology of pneumonia is associated with gram-negative bacteria in malnourished children. To anatomize the molecular mechanisms, we focused on the modulatory function of circular RNA-Atp9b (circAtp9b) on inflammation in which microRNA-27a (miR-27a) might be implicated.

Methods: MRC-5 cells were stimulated by lipopolysaccharide (LPS) to exhibit inflammatory lesions assessed by viability and apoptosis as well as the cleavage of caspase-3, production of interleukin-6 and tumor necrosis factor alpha, and generation of reactive oxygen species (ROS). circAtp9b and miR-27a were quantified by qRT-PCR. circAtp9b- or miR-27a-silenced MRC-5 cells were established to study their roles in inflammation. Moreover, the change of NF-κB and JNK pathways was monitored.

Results: LPS was observed to induce adverse inflammatory injuries by repressing viability and fortified apoptosis with cleavage of caspase-3, production of cytokines, formation of ROS and abundance of circAtp9b. The results suggested circAtp9b silence prevented MRC-5 cells from LPS-elicited insults, which was accompanied by blockage of NF-κB and JNK. circAtp9b silence restored miR-27a which was repressed by LPS. miR-27a knockdown abrogated the protective capacities of circAtp9b silence with activation of NF-κB and JNK in response to LPS.

Conclusion: LPS triggered adverse inflammation response by elevating the biogenesis of circAtp9b which caused a repressive role in miR-27a expression.

Keywords: JNK; MRC-5 cells; NF-κB; Pneumonia; TLR4.