MiR-223 plays a protecting role in neutrophilic asthmatic mice through the inhibition of NLRP3 inflammasome

Abstract

Background: Neutrophilic subtype asthma occurs in approximately 15-25% of the asthma cases and is associated with severe airflow obstruction, corticosteroid resistance. MicroRNA plays a vital role in regulating many immune processes, but how miRNA circuits coordinate airway inflammation during neutrophilic asthma is unclear. Methods: To investigate the molecular mechanism of miR-223 in regulation of neutrophilic airway inflammation, miR-223 knockout mice were used to the OVA/CFA-induced neutrophilic asthma or treated with NLRP3 inhibitor and IL-1β receptor antagonist. Based on the results obtained, wide-type mice were subsequently treated with miR-223 agomirs or negative control agomirs, and the effects on airway inflammation were assessed using morphometric techniques, quantitative RT-PCR, western blot, ELISA and other molecular approaches. Results: The expression of miR-223 was upregulated in lung tissues of experimental mice model. Furthermore, miR-223 −/− mice led to aggravated neutrophilic airway inflammation with heightened histopathological, inflammatory cells and cytokines readouts. Moreover, miR-223 −/− mice also presented with enhanced NLRP3 inflammasome level with elevated IL-1β. Blocking NLRP3 or IL-1β diminished this phenotype. Finally, overexpression of miR-223 via treatment with miR-223 agomirs attenuated airway inflammation, NLRP3 levels and IL-1β release. Conclusions: The findings of this study revealed a crucial role for miR-223 in regulating the immunoinflammatory responses by depressing the NLRP3/ IL-1β axis in neutrophilic asthma.

MicroRNAs as Potential Regulators of Immune Response Networks in Asthma and Chronic Obstructive Pulmonary Disease

“…However, some have been studied more in depth, showing a high potential as future therapeutic tools through their up- or downregulation. In this sense, miR-146a ( 79 , 89 ), miR-21 ( 113 , 116 ), miR-150 ( 109 ), miR-145-5p ( 131 , 148 ), miR-320d ( 132 , 144 ), miR-155 ( 62 ) miR-223 ( 211 ), or miR-3162-3p ( 212 ) seem to hold promise as future elements in the therapeutic repertoire for COPD and asthma, respectively, some of which are common for both pathologies such as miR-146a ( 213 – 215 ) or miR-21 ( 54 , 62 ).…”

Ethyl Pyruvate Attenuates Microglial NLRP3 Inflammasome Activation via Inhibition of HMGB1/NF-κB/miR-223 Signaling

“…In macrophages, polarization states differ in terms of miR-223 expression; M2 polarization shows increased expression of miR-223, while in M1 polarization, miR-223 is downregulated [ 42 ]. Furthermore, miR-223 was previously shown to negatively regulate NLRP3 inflammasome activation in vitro and in vivo [ 11 , 43 , 44 ]. It was also recently reported that miR-223 directly targets NLRP3 inflammasome to reduce LPS-induced inflammatory responses [ 45 ].…”

Down-regulated gga-miR-223 inhibits proliferation and induces apoptosis of MG-infected DF-1 cells by targeting FOXO3

“…Importantly, accumulating data has suggested that miR-223 plays an important role in various diseases, especially respiratory disease [20,38,39]. MiR-223 plays a key role in regulating the immune in ammatory response to neutrophil asthma by inhibiting the NLRP3/ IL-1β [40]; pharmacological blockade of the miR-223-NLRP3-IL-1β signaling axis alleviates acute respiratory distress syndrome [41]. In addition, the expression level of miR-223 has dramatically altered by other bacterial infections, For instance, gastric in ammation caused by Helicobacter pylori infection through induction of miR-223-3P expression in a Helicobacter pylori CagA-dependent manner [42]; the expression of miR-223 in the breast tissue of dairy cows with Streptococcus agalactis mastitis increased three-fold, which may be involved in the signal pathway of Streptococcus agalactis-induced mastitis [40].…”