MicroRNA‑223 attenuates LPS‑induced inflammation in an acute lung injury model via the NLRP3 inflammasome and TLR4/NF‑κB signaling pathway via RHOB

Abstract

Acute lung injury (ALI) and the more severe acute respiratory distress syndrome are common and complex inflammatory lung diseases. MicroRNAs (miRs) have emerged as novel gene regulatory molecules, serving a crucial role in a variety of complex diseases, including ALI. In the present study, the anti-inflammatory action of miR-223 on inflammation in ALI was demonstrated and the possible mechanism was further examined. In lipopoly-saccharide-induced ALI, the expression of miR-223 was reduced compared with that in the control normal group. An in vitro model was used to analyze the effect of miR-223 downregulation on an ALI model, which increased inflammation, and induced the activation of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome and Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway via rho-related GTP-binding protein RhoB (RHOB). In addition, the overexpression of miR-223 reduced inflammation and suppressed the NLRP3 inflammasome and TLR4/NF-κB signaling pathway via RHOB in the in vitro model. Furthermore, TLR4 inhibitor or NLRP3 inhibitor reduced the pro-inflammatory effect of miR-223 downregulation in ALI. In conclusion, the results of the present study indicated that miR-223 functioned as a biological indicator by regulating inflammation in ALI, and may represent a novel potential therapeutic target and prognostic marker of ALI.

Aerobic Exercise Inhibits CUMS-Depressed Mice Hippocampal Inflammatory Response via Activating Hippocampal miR-223/TLR4/MyD88-NF-κB Pathway

“…The previous study found that the expression of miR-223 was enhanced after TLR4 was inhibited. This was in contrast to Yan et al [52], where downregulation of miR-223 induced the upregulation of TLR4, NF-κB, and NLRP3, while inhibiting TLR4 in vitro reduced the release of in vitro inflammatory factors following the downregulation of miR-223. This confirmed that miR-223 targets the role of TLR4 in the inflammatory response.…”

MiR-802 alleviates lipopolysaccharide-induced acute lung injury by targeting Peli2

“…Overexpressing miR-233 can attenuate LPS-mediated inflammation in the disease model. Interestingly, miR-233 has been also found to inhibit NLRP3 inflammasome by targeting rho-related GTPbinding protein RhoB (RHOB) [19]. In another study, miR-155 has been reported being elevated in bronchoalveolar lavage fluid (BALF) samples of ARDS patients.…”

Inflammation and Inflammasomes: Pros and Cons in Tumorigenesis

“…Studies realized for understanding oral squamous cell carcinoma mechanisms and revealed that overexpression of both miR-223 and miR-22 suppressed NLRP3 inflammasome and NF- κ B signaling through ras homolog family member B (RHOB) and were considered as potential therapy targets [ 142 ]. Similar results were obtained studying cervical cancer pathogenicity, where it was observed that overexpression of miR-223 suppressed FOXO1, reduced proliferation of tumor cells, and regulated the inflammasome complex activation through the NF- κ B signaling pathway [ 143 ].…”