MicroRNA-26b Modulates the NF-κB Pathway in Alveolar Macrophages by Regulating PTEN

Abstract

NF-κB is one of the best-characterized transcription factors, providing the link between early membrane-proximal signaling events and changes in many inflammatory genes. MicroRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Here, we evaluated the role of miR-26b in lipopolysaccharide (LPS)-induced inflammatory response in bovine alveolar macrophages (bAMs). LPS stimulation of bAMs upregulated miR-26b at 1 h, and down-regulated miR-26b at 6 and 36 h. Overexpression of miR-26b in bAMs enhanced the LPS-induced mRNA expression of proinflammatory cytokines and chemokines including TNF-α, IL-1β, IL-8, , IL-10, but directly inhibited that of IL-6. The similar trend was observed for the release of these cytokines and chemokines from bAMs. miR-26b directly bound the 3’-untranslated region of PTEN, leading to the reduction of PTEN protein in bAMs. miR-26b also enhanced the LPS-induced NF-κB signaling pathway as revealed by increased NFκB transcriptional activity and phosphorylation of p65, IκBα, Ikk and Akt. Moreover, PTEN silencing increased the LPS-induced mRNA expression of TNF-α, IL-1β, IL-6, IL-8, and IL-10, and up-regulated the NF-κB pathway. Taken together, we conclude that miR-26b participates in the inflammatory response of LPS-stimulated bAMs by modulating the NF-κB pathway through targeting PTEN.

MicroRNA-27b Modulates Inflammatory Response and Apoptosis duringMycobacterium tuberculosisInfection

“…Several miRNAs are involved in regulating the NF-kB pathway. For example, miR-26b enhances the LPS-induced NF-kB signaling pathway and the production of proinflammatory factors by targeting PTEN (54). Furthermore, miR-3570 inhibits the bacteria-induced inflammatory response of miiuy croaker via the MyD88-mediated NF-kB signaling pathway by targeting MyD88 (55).…”

Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Active Tuberculosis Patients

“…We found that the potential miRNAs targets of hsa_circRNA_001937 include miR-22-5p, miR-26b-3p, miR-10b-3p, miR-376a-5p and miR-597-3p. MiR-26b participates in the inflammatory response by modulating the NF-κB pathway through targeting PTEN [25]. However, due to the limited known function of circRNAs and miRNAs, a lot of circRNAs/miRNAs interactions should be analyzed in the future.…”

Integration of Canonical and Noncanonical Pathways in TLR4 Signaling: Complex Regulation of the Wound Repair Program

“…PTEN, however, interacts with PPM1A in scleroderma 65 and PTEN silencing in macrophages increased LPS-induced expression of TNF-a, IL-1b, IL-6, IL-8, and IL-10. 66 There are apparently contrary findings, however. LPS activation of TLR4 also stimulates miR-718 expression (in macrophages), which impacts PI3K/Akt signaling by targeting PTEN, promoting Akt phosphorylation leading to a decrease in the production of proinflammatory cytokines.…”