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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4591-4597. Prepublished online as a Blood First Edition Paper on September 12, 2008; DOI 10.1182/blood-2008-04-152488. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-04-152488v1 112/12/4591    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dai, R. Articles by Ahmed, S. A. Search for Related Content PubMed PubMed Citation Articles by Dai, R. Articles by Ahmed, S. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 18, 2008 Accepted August 10, 2008 Suppression of LPS-induced IFN and nitric oxide in splenic lymphocytes by select estrogen-regulated miRNA: A novel mechanism of immune modulation Rujuan Dai, Rebecca A. Phillips, Yan Zhang, Deena Khan, Oswald Crasta, and S. Ansar Ahmed* Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, VA, United States Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States * Corresponding author; email: ansrahmd{at}vt.edu. microRNA (miRNA), recently identified, non-coding, small RNA, are emerging as key regulators in homeostasis of the immune system. Therefore, aberrant expression of miRNA may be linked to immune dysfunction, such as in chronic inflammation and autoimmunity. In this study, we investigated the potential role of miRNA in estrogen-mediated regulation of innate immune responses, as indicated by upregulation of LPS-induced IFN, inducible nitric oxide synthase (iNOS), and nitric oxide in splenic lymphocytes from estrogen-treated mice. We found that miR-146a, a negative regulator of Toll-like receptor (TLR) signaling, was decreased in freshly-isolated splenic lymphocytes from estrogen-treated mice compared to placebo controls. Increasing the activity of miR-146a significantly inhibited LPS-induced IFN and iNOS expression in mouse splenic lymphocytes. Further, miRNA microarray and Real-time RT-PCR analysis revealed that estrogen selectively upregulates/downregulates the expression of miRNA in mouse splenic lymphocytes. miR-223, which is highly upregulated by estrogen, regulates LPS-induced IFN, but not iNOS or nitric oxide in splenic lymphocytes. Inhibition of miR-223 activity decreased LPS-induced IFN in splenic lymphocytes from estrogen-treated mice. Our data are the first to demonstrate the selective regulation of miRNA expression in immune cells by estrogen and are indicative of an important role of miRNA in estrogen-mediated immune regulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Dai, R. A. Phillips, E. Karpuzoglu, D. Khan, and S. A. Ahmed Estrogen Regulates Transcription Factors STAT-1 and NF-{kappa}B to Promote Inducible Nitric Oxide Synthase and Inflammatory Responses J. Immunol., December 1, 2009; 183(11): 6998 - 7005. [Abstract] [Full Text] [PDF] E. M. C. Ohlsson Teague, C. G. Print, and M. L. Hull The role of microRNAs in endometriosis and associated reproductive conditions Hum. Reprod. Update, September 22, 2009; (2009) dmp034v1. [Abstract] [Full Text] [PDF] J. Hou, P. Wang, L. Lin, X. Liu, F. Ma, H. An, Z. Wang, and X. Cao MicroRNA-146a Feedback Inhibits RIG-I-Dependent Type I IFN Production in Macrophages by Targeting TRAF6, IRAK1, and IRAK2 J. Immunol., August 1, 2009; 183(3): 2150 - 2158. [Abstract] [Full Text] [PDF]

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