title: MicroRNA let-7f: a novel regulator of innate immune response in human endocervical cells.
abstract: OBJECTIVE
  Endocervical epithelial cells express pattern recognition receptors (PRRs) that aid in innate immune responses. Mechanisms regulating signaling of PRRs are poorly understood.
  
  
  METHODS
  Endocervical cells (End1/E6E7) were treated with ligands of TLR9 and RIG-I once or after pre-stimulation with same ligand. Cytokine responses were determined by ELISA. Differential gene expression was analyzed by microarray. Differentially expressed genes were validated by qPCR /Western blot. Role of let-7f was studied by inhibition and over-expression studies using commercial inhibitors and let-7f encoding plasmids, respectively.
  
  
  RESULTS
  Single stimulation of cells with TLR9 ligand, but not RIG-I ligand, induced tolerance to subsequent challenge to the same ligand. Stimulation with TLR9 decreased let-7f and increased its target Blimp-1. Conversely, RIG-I stimulation increased let-7f and decreased Blimp-1 expression. Inhibition and over-expression revealed let-7f is involved in induction of immune tolerance.
  
  
  CONCLUSIONS
  We identify let-7f as a novel regulator of PRR signaling in endocervical cells.
authors.affiliation: Division of Molecular Immunology and Microbiology (MIM), National Institute for Research in Reproductive Health (ICMR), Mumbai, India.
authors.forename: Ameya
authors.initials: A
authors.lastname: Sathe
authors.forename: Mandar S
authors.initials: MS
authors.lastname: Patgaonkar
authors.forename: Tahir
authors.initials: T
authors.lastname: Bashir
authors.forename: Kudumula Venkata Rami
authors.initials: KV
authors.lastname: Reddy
mesh_terms: D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007113:Immunity, Innate; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D011971:Receptors, Immunologic; D051217:Toll-Like Receptor 9 / Q000819:agonists; D059467:Transcriptome; D019076:Transgenes / Q000235:genetics
chemical_list: C513533:CpG ODN 2006; D006877:Hydroxamic Acids; D035683:MicroRNAs; D009838:Oligodeoxyribonucleotides; D011971:Receptors, Immunologic; D051217:Toll-Like Receptor 9; C487931:mirnlet7 microRNA, human; C012589:trichostatin A; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D011070:Poly I-C
keywords: Blimp1; cytokines; let-7f; miRNA; pathogen recognition receptors; tolerance