Attenuated lncRNA NKILA Enhances the Secretory Function of Airway Epithelial Cells Stimulated by Mycoplasma pneumoniae via NF-κB

Abstract

The secretory function of airway epithelial cells is important in the pathogenesis of Mycoplasma pneumoniae pneumonia (MPP). To investigate the regulatory function of NKILA (nuclear factor-κB (NF-κB) interacting long noncoding RNA (lncRNA)) in MPP, we first detected NKILA as well as the concentration of interleukin 8 (IL-8) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid of children with MPP. Then, NKILA was knocked down in epithelial cells to investigate its effect on their secretory function. The results suggested that NKILA was downregulated in children with MPP, while IL-8 and TNF-α levels increased. Knockdown of NKILA in vitro promoted the inflammatory effects of Mycoplasma pneumoniae (MP) in epithelial A549 and BEAS-2B cells. Knockdown of NKILA promoted inhibitor of κBα (IκBα) phosphorylation and degradation, and NF-κB p65 nuclear translocation. Furthermore, RNA immunoprecipitation showed that NKILA could physically bind to IκBα in MP-treated A549 cells. Collectively, our data demonstrated that attenuation of NKILA enhances the effects of MP-stimulated secretory functions of epithelial cells via regulation of NF-κB signaling.

Influence of LncRNA NKILA on Bloodstream Infection of Hypervirulent Klebsiella pneumoniae and Its Ability to Induce Delayed Neutrophil Apoptosis

“…Referring to the relevant research, we found that some special genes on virulence plasmids are considered to be the best markers for identifying hvKP at present [ 10 ]. Among them, lncRNA NKILA (NKILA) is a gene that has been proved to be abnormally expressed in patients with sepsis and HIV-1 infection [ 11 , 12 ]; as for pneumonia, NKILA has also been found to exert a certain regulatory effect on the epithelial cytotoxicity of mycoplasma pneumoniae [ 13 ]. Therefore, we speculate that NKILA may also have important reference significance in hvKP.…”

Pathogenic mycoplasmas of humans regulate the long noncoding RNAs in epithelial cells

“…Since many of the highly dysregulated lncRNA genes by Mg and Mp are new and their functions in the cellular processes are yet to be determined, we wanted to know whether Mg and Mp regulate any of the lncRNAs that were previously implicated in infection and immune response [ 10 , [22] , [23] , [24] , 51 , 52 ]. To accomplish this, a list of about thirty lncRNA genes ( Table S10 ) with known functions in infection and immune response was made, and their presence or absence was tracked within the lncRNAs up- and down-regulated by Mg or Mp or by both.…”

“…Further, it was previously reported that MALAT1 expression is higher [ 51 ] and NKILA, another lncRNA, expression is lower in the bronchoalveolar lavage fluid of children with Mp-related pneumonia than in the control subjects without pneumonia [ 52 ]. Human alveolar epithelial cell lines A549 infected with Mp also showed a similar trend of higher MALAT1 expression and lower NKILA expression accompanied by increased IL-8 and TNF-α [ 51 , 52 ]. It should be noted here that the expression of NKILA is downregulated in Mp-infected HeLa cells, although it was neither upregulated nor downregulated in Mg-infected HeLa cells ( Table 1 ).…”

“…It should be noted here that the expression of NKILA is downregulated in Mp-infected HeLa cells, although it was neither upregulated nor downregulated in Mg-infected HeLa cells ( Table 1 ). Interestingly, MALAT1 and NKILA modulate cytokine expression through the NF-κB pathway [ 51 , 52 ]. Whereas the downregulation of MALAT1 inhibits the phosphorylation of p65 (NF-κB), the downregulation of NKILA enhances the translocation of phosphorylated p65 to the nucleus [ 51 , 52 ].…”

“…This notion is supported by the limited literature on Mp infection in humans. For instance, lncRNAs MALAT1 and NKILA are up- and down-regulated in the bronchoalveolar lavage fluid of children with Mp-related pneumonia (MPP) [ 51 , 52 ]. Also, the lncRNA NNT-AS1 is at higher levels in the serum samples of patients from the refractory Mp-pneumonia (RMPP) [ 53 ].…”