LINC00998 Modulating M2 Macrophage Activation in Allergic Rhinitis by Stabilizing BOB.1 mRNA.

ABSTRACT

Background: Allergic rhinitis (AR) is globally recognized as a considerable threat to human health with a rising prevalence and a substantial medical and socioeconomic burden. Numerous studies have emphasized the significance of long noncoding RNAs (lncRNAs) in allergic responses. Hence, this research dealt with exploring the involvement of the lncRNA LINC00998 in the mechanism of AR. Methods: LINC00998 expression was assessed by qRT-PCR in peripheral blood mononuclear cells acquired from individuals with AR. Additionally, the potential relationship between LINC00998 and macrophage polarization was observed in vitro. Then we constructed AR mice model and macrophage polarization models using THP-1 cells as well as primary human macrophages to verify the M2 shift in AR and the low expression level of LINC00998 in M2 macrophages. We used gain- and loss-of-function experiments to explore the modification of LINC00998 in macrophage polarization. Furthermore, we explored the underlying mechanism of LINC00998 mediates through qRT-PCR, flow cytometry, and Western blot. Results: The analysis revealed a significant decrease in LINC00998 expression in the samples obtained from patients with AR. LINC00998 is markedly increased in M1 macrophages whereas decreased in M2 macrophages in vitro. Furthermore, suppression of LINC00998 caused a remarkable enhancement in M2 polarization, whereas its overexpression led to its attenuation. Knockdown of LINC00998 led to a remarkable downregulation of BOB.1 mRNA and protein, while overexpression of LINC00998 upregulated their expression. Moreover, it was found that BOB.1 modulated macrophage polarization through the PU.1/IL-1ß axis. Meanwhile, the modulation of LINC00098 overexpression on macrophage polarization and PU.1/ IL-1ß can be reversed by BOB.1 siRNA. Conclusion: This research revealed the lncRNA LINC00998 altered M2 macrophage polarization by regulating the BOB.1/PU.1/IL-1ß axis, which open up new avenues for studying the pathogenesis of AR.