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Formation of GW/P bodies as marker for microRNA‐mediated regulation of innate immune signaling in THP‐1 cells
Author(s) -
Pauley Kaleb M,
Satoh Minoru,
Pauley Brad A,
DominguezGutierrez Paul R,
Wallet Shan M,
Holliday L Shan,
Cha Seunghee,
Reeves Westley H,
Chan Edward KL
Publication year - 2010
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2009.84
Subject(s) - microrna , chemokine , biology , microbiology and biotechnology , innate immune system , stimulation , transfection , gene knockdown , cytokine , effector , thp1 cell line , immune system , signal transduction , immunology , cell culture , gene , endocrinology , genetics
GW bodies (GWB or P bodies) are cytoplasmic foci thought to result from microRNA (miRNA) regulation of messenger RNA (mRNA) targets and subsequent mRNA degradation. The purpose of this study is to examine the effects of lipopolysaccharide (LPS) stimulation of human monocytes on GWB formation, miRNA induction, miRNA target regulation and downstream cytokine and chemokine expression. In response to LPS stimulation, the number of GWB consistently increased by twofold at 8 h after stimulation and this increase was abolished when the miRNA‐effector proteins Rck/p54 or argonaute 2 were depleted. As the level of miR‐146a increased from 19‐fold up to 100‐fold during LPS stimulation, the transfection of a miR‐146a mimic into THP‐1 cells was examined to determine whether miR‐146a alone can induce similar changes in GWB. The results showed transfected miR‐146a could produce a comparable increase in the number of GWB and this was accompanied by a reduction in major cytokines/chemokines induced by LPS. These data show that the increase in size and number of GWB may serve as a biomarker for miRNA‐mediated gene regulation, and miR‐146a has a significant role in the regulation of LPS‐induced cytokine production in THP‐1 cells.