title: MicroRNA-21 inhibits toll-like receptor 2 agonist-induced lung inflammation in mice.
abstract: Impaired airway innate immunity (e.g., suppressed Toll-like receptor 2 [TLR2] signaling) has been reported in allergic lungs with bacterial infection. Recently, an allergic mouse lung milieu including the T-helper type 2 (Th2) cytokine interleukin-13 (IL-13) has been shown to up-regulate lung microRNA-21 (miR-21) expression. Whether miR-21 modulates in vivo TLR2 signaling is unknown. The goal of this study was to determine if in vivo, miR-21 regulates a TLR2 agonist-induced lung inflammatory response. Balb/c mice were intranasally pretreated with a locked nucleic acid (LNA) in vivo inhibitor probe for mouse miR-21 or a control probe, followed by intranasal instillation of a TLR2 agonist Pam3CSK4, or saline (control). Four and/or 24 hours later, mice treated with the miR-21 inhibitor probe, as compared to the control probe, significantly increased lung leukocytes, including neutrophils and the keratinocyte-derived chemokine (KC). IL-13 treatment for 72 hours increased (P < .05) miR-21 in cultured primary normal human airway epithelial cells. These results, for the first time, suggest an in vivo role of miR-21 in suppressing TLR2 signaling, and further support that IL-13 can up-regulate miR-21 in human airway epithelial cells. Functional studies on miR-21 likely provide novel approaches to modulate TLR2 signaling in Th2 cytokine-exposed airways.
authors: Department of Medicine, National Jewish Health, Denver, Colorado, USA.
authors: Stephanie R
authors: SR
authors: Case
authors: Richard J
authors: RJ
authors: Martin
authors: Di
authors: D
authors: Jiang
authors: Maisha N
authors: MN
authors: Minor
authors: Hong Wei
authors: HW
authors: Chu
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007113:Immunity, Innate; D018793:Interleukin-13 / Q000494:pharmacology; D055666:Lipopeptides / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018793:Interleukin-13; D055666:Lipopeptides; C524940:MIRN21 microRNA, human; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; C508075:Pam(3)CSK(4) peptide; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2