MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8

Bhaumik, Dipa; Scott, Gary K.; Schokrpur, Shiruyeh; Patil, Christopher K.; Orjalo, Arturo V.; Rodier, Francis; Lithgow, Gordon J.; Campisi, Judith

doi:10.18632/aging.100042

MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8

Journal Article · Thu Apr 09 00:00:00 EDT 2009 · Aging

DOI:https://doi.org/10.18632/aging.100042· OSTI ID:1627966

Bhaumik, Dipa ^[1]; Scott, Gary K. ^[2]; Schokrpur, Shiruyeh ^[2]; Patil, Christopher K. ^[3]; Orjalo, Arturo V. ^[2]; Rodier, Francis ^[3]; Lithgow, Gordon J. ^[2]; Campisi, Judith ^[3]

Buck Institute for Age Research, Novato, CA (United States); DOE/OSTI
Buck Institute for Age Research, Novato, CA (United States)
Buck Institute for Age Research, Novato, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Senescence is a cellular program that irreversibly arrests the proliferation of damaged cells and induces the secretion of the inflammatory mediators IL- 6 and IL-8 which are part of a larger senescence associated secretory phenotype (SASP). We screened quiescent and senescent human fibroblasts for differentially expressed microRNAS (miRNAs) and found that miRNAs 146a and 146b (miR-146a/b) were significantly elevated during senescence. We suggest that delayed miR-146a/b induction might be a compensatory response to restrain inflammation. Indeed, ectopic expression of miR-146a/b in primary human fibroblasts suppressed IL-6 and IL-8 secretion and downregulated IRAK1, a crucial component of the IL-1 receptor signal transduction pathway. Cells undergoing senescence without induction of a robust SASP did not express miR-146a/b. Further, IL-1α neutralizing antibodies abolished both miR-146a/b expression and IL-6 secretion. Our findings expand the biological contexts in which miRNA-146a/b modulates inflammatory responses. They suggest that IL-1 receptor signaling initiates both miR-146a/b upregulation and cytokine secretion, and that miR- 146a/b is expressed in response to rising inflammatory cytokine levels as part of a negative feedback loop that restrains excessive SASP activity.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1627966

Journal Information:: Aging, Journal Name: Aging Journal Issue: 4 Vol. 1; ISSN 1945-4589

Publisher:: Impact Journals, LLCCopyright Statement

Country of Publication:: United States

Language:: English

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Mutant lamin A links prophase to a p53 independent senescence program Moiseeva, Olga; Lessard, Frédéric; Acevedo-Aquino, Mariana Taylor & Francis https://doi.org/10.6084/m9.figshare.1468563.v2	text	January 2015
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Targeted delivery of microRNA 146b mimic to hepatocytes by lactosylated PDMAEMA nanoparticles for the treatment of NAFLD He, Shuying; Guo, Weihong; Deng, Feihong Taylor & Francis https://doi.org/10.6084/m9.figshare.6010826.v2	text	January 2019

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