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Divergent intracellular pathways regulate interleukin‐1β‐induced miR‐146a and miR‐146b expression and chemokine release in human alveolar epithelial cells
Author(s) -
Perry Mark M.,
Williams Andrew E.,
Tsitsiou Eleni,
Larner-Svensson Hanna M.,
Lindsay Mark A.
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.09.038
Subject(s) - microbiology and biotechnology , chemokine , p38 mitogen activated protein kinases , intracellular , mapk/erk pathway , mitogen activated protein kinase , kinase , signal transduction , extracellular , interleukin 8 , chemistry , biology , inflammation , immunology
We have previously reported that IL‐β‐induced miR‐146a and miR‐146b expression negatively regulates IL‐8 and RANTES release in human alveolar A549 epithelial cells. To determine the intracellular pathways that regulate this response, we demonstrate IL‐1β‐induced activation of the nuclear factor (NF)‐κB, extracellular regulated kinase (ERK)‐1/2, c‐jun N‐terminal kinase (JNK)‐1/2 and p38 mitogen activated kinase (MAP) kinase pathways. Subsequent pharmacological studies show that IL‐1β‐induced miR‐146a, IL‐8 and RANTES production was regulated via NF‐κB and JNK‐1/2 whilst miR‐146b expression was mediated via MEK‐1/2 and JNK‐1/2. These divergent intracellular pathways likely explain the differential expression and biological action of the miR‐146 isoforms.