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MicroRNA-26b Modulates the NF-κB Pathway in Alveolar Macrophages by Regulating PTEN.
J Immunol. 2015 Dec 01; 195(11):5404-14.JI

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.

Authors+Show Affiliations

Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078; Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Oklahoma State University, Stillwater, OK 74078; Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078; and.Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078; Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Oklahoma State University, Stillwater, OK 74078; Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078; and.Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078; Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Oklahoma State University, Stillwater, OK 74078; Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078; and.Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078; Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Oklahoma State University, Stillwater, OK 74078; Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078; and.Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078; Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078; and Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 74126.Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078; Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078; and.Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK 74078; Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Oklahoma State University, Stillwater, OK 74078; Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078; and lin.liu@okstate.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

26503952

Citation

Zhang, Li, et al. "MicroRNA-26b Modulates the NF-κB Pathway in Alveolar Macrophages By Regulating PTEN." Journal of Immunology (Baltimore, Md. : 1950), vol. 195, no. 11, 2015, pp. 5404-14.
Zhang L, Huang C, Guo Y, et al. MicroRNA-26b Modulates the NF-κB Pathway in Alveolar Macrophages by Regulating PTEN. J Immunol. 2015;195(11):5404-14.
Zhang, L., Huang, C., Guo, Y., Gou, X., Hinsdale, M., Lloyd, P., & Liu, L. (2015). MicroRNA-26b Modulates the NF-κB Pathway in Alveolar Macrophages by Regulating PTEN. Journal of Immunology (Baltimore, Md. : 1950), 195(11), 5404-14. https://doi.org/10.4049/jimmunol.1402933
Zhang L, et al. MicroRNA-26b Modulates the NF-κB Pathway in Alveolar Macrophages By Regulating PTEN. J Immunol. 2015 Dec 1;195(11):5404-14. PubMed PMID: 26503952.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-26b Modulates the NF-κB Pathway in Alveolar Macrophages by Regulating PTEN. AU - Zhang,Li, AU - Huang,Chaoqun, AU - Guo,Yujie, AU - Gou,Xuxu, AU - Hinsdale,Myron, AU - Lloyd,Pamela, AU - Liu,Lin, Y1 - 2015/10/26/ PY - 2014/11/24/received PY - 2015/09/23/accepted PY - 2015/10/28/entrez PY - 2015/10/28/pubmed PY - 2016/3/16/medline SP - 5404 EP - 14 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 195 IS - 11 N2 - 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. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/26503952/MicroRNA_26b_Modulates_the_NF_��B_Pathway_in_Alveolar_Macrophages_by_Regulating_PTEN_ DB - PRIME DP - Unbound Medicine ER -