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Micro RNA Let‐7f: A Novel Regulator of Innate Immune Response in Human Endocervical Cells
Author(s) -
Sathe Ameya,
Patgaonkar Mandar S.,
Bashir Tahir,
Reddy Kudumula Venkata Rami
Publication year - 2014
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12165
Subject(s) - regulator , innate immune system , immune system , microbiology and biotechnology , rna , biology , immunology , chemistry , gene , biochemistry
Problem Endocervical epithelial cells express pattern recognition receptors ( PRR s) that aid in innate immune responses. Mechanisms regulating signaling of PRR s are poorly understood. Methods of Study 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 TLR 9 ligand, but not RIG ‐I ligand, induced tolerance to subsequent challenge to the same ligand. Stimulation with TLR 9 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. Conclusion We identify let‐7f as a novel regulator of PRR signaling in endocervical cells.