NF-κB-Induced MicroRNA-211 Inhibits Interleukin-10 in Macrophages of Rats with Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome

Abstract

Background/Aims: The present study addressed the potential involvement of microRNAs in acute respiratory distress syndrome (ARDS)-related inflammation and elucidates the underlying molecular mechanism. Methods: ARDS rat model was established by lipopolysaccharide, with compromised gas exchange capacity and lung edema. The inflammatory cells from bronchoalveolar lavage fluid (BALF) were profiled with automatic blood cell analyzer. The relative fluorescence intensity of BALF-derived macrophages was analyzed by flow cytometry. The relative microRNA expression was determined using microarray and Taqman assay. The secretory interleukin (IL)-10 was measured by enzyme-linked immunosorbent assay. Luciferase reporter assay was performed to determine the regulatory effects of miR-211 and NF-κB on IL-10 and miR-211 expressions, respectively. Chromatin immunoprecipitation (ChIP) was conducted to detect the direct binding of NK-κB on miR-211 promoter. The protein level was determined by Western blot. Results: The provoked acute inflammation was characterized with increased total cells, macrophages, neutrophils and lymphocytes. The relative expression of miR-211 was aberrantly up-regulated in BALF-derived macrophages from ARDS rats, which was accompanied with reduction of secretory IL-10. We further demonstrated that miR-211 inhibited IL-10 expression by binding to its 3’-UTR. The expression of miR-211 was modulated by NF-κB. Conclusion: Here we elucidated a crucial role of NF-κB/miR-211/IL-10 signaling axis in ARDS-related inflammation.

miR-155-5p Promotes Progression of Acute Respiratory Distress Syndrome by Inhibiting Differentiation of Bone Marrow Mesenchymal Stem Cells to Alveolar Type II Epithelial Cells

“…Many studies have proven that microRNA can mediate the development of ARDS. For example, NF-κB-induced microRNA-211 inhibits IL-10 in macrophages of rats with LPS-induced ARDS [28] [29 40 28 31]. In the present study, microRNA-155-5p expression was significantly elevated in ARDS patients.…”

MicroRNA-138 Aggravates Inflammatory Responses of Macrophages by Targeting SIRT1 and Regulating the NF-κB and AKT Pathways

“…Depending on different circumstances, macrophages may differentiate into two different phenotypes. M1 macrophages (or classically activated macrophage) are pro-inflammatory macrophages that release IL-1β, TNF-α, IL-6 and other inflammatory factors under the stimulation of IFN-γ or lipopolysaccharide (LPS) through the activation of the STAT1 or NF-κB pathway [7,8]. These inflammatory factors are also important cytokines increased in sepsis during severe inflammatory periods.…”

Elevated IL-33 promotes expression of MMP2 and MMP9 via activating STAT3 in alveolar macrophages during LPS-induced acute lung injury

“…AMs, once activated by toll-like receptors (TLRs), serve as the first line of defense against invaders into the lung [ 15 ]. Wang et al reported that the NF-κB pathway aberrantly activated in BALF-derived macrophages aroused ARDS in rats [ 16 ]. Therefore, we supposed that the LPS-induced IL-33 secretion requires activation of the TLR4/NF-κB pathway since NF-κB is the central mediator of inflammation.…”