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 noncoding RNAs that regulate gene expression at the posttranscriptional level. In this study, we evaluated the role of miR-26b in the LPS-induced inflammatory response in bovine alveolar macrophages (bAMs). LPS stimulation of bAMs upregulated miR-26b at 1 h and downregulated it 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, and IL-10, but it directly inhibited that of IL-6. A 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 NF-κB transcriptional activity and phosphorylation of p65, IκBα, IκB kinase, and Akt. Moreover, PTEN silencing increased the LPS-induced mRNA expression of TNF-α, IL-1β, IL-6, IL-8, and IL-10 and upregulated 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.