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PMID: 21940629 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Glucocorticoids sensitize the innate immune system through regulation of the NLRP3 inflammasome.

The Journal of biological chemistry ·Vol. 286 ·No. 44 ·2011-11-04 ·Pages 38703-38713

Busillo JM, Azzam KM, Cidlowski JA

Abstract

Glucocorticoids have long been recognized as powerful anti-inflammatory compounds that are one of the most widely prescribed classes of drugs in the world. However, their role in the regulation of innate immunity is not well understood. We sought to examine the effects of glucocorticoids on the NOD-like receptors (NLRs), a central component of the inflammasome and innate immunity. Surprisingly, we show that glucocorticoids induce both NLRP3 messenger RNA and protein, which is a critical component of the inflammasome. The glucocorticoid-dependent induction of NLRP3 sensitizes the cells to extracellular ATP and significantly enhances the ATP-mediated release of proinflammatory molecules, including mature IL-1β, TNF-α, and IL-6. This effect was specific for glucocorticoids and dependent on the glucocorticoid receptor. These studies demonstrate a novel role for glucocorticoids in sensitizing the initial inflammatory response by the innate immune system.

MeSH Terms
Adenosine Triphosphate/chemistry Animals Bone Marrow Cells/cytology Carrier Proteins/metabolism Glucocorticoids/metabolism Immunity, Innate Inflammation Interleukin-1beta/metabolism Interleukin-6/metabolism Macrophages/cytology Mice Mice, Inbred C57BL NLR Family, Pyrin Domain-Containing 3 Protein Receptors, Glucocorticoid/metabolism Tumor Necrosis Factor-alpha/metabolism
Chemicals
Carrier Proteins Glucocorticoids Interleukin-1beta Interleukin-6 NLR Family, Pyrin Domain-Containing 3 Protein NLRP3 protein, human Nlrp3 protein, mouse Receptors, Glucocorticoid Tumor Necrosis Factor-alpha Adenosine Triphosphate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Busillo John M
Laboratory of Signal Transduction, Department of Health and Human Services, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Azzam Kathleen M
Laboratory of Respiratory Biology, Department of Health and Human Services, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Cidlowski John A
Laboratory of Signal Transduction, Department of Health and Human Services, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709. Electronic address: cidlows1@niehs.nih.gov.
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M111.275370
Email
cidlows1@niehs.nih.gov
Published
2011-11-04
Epub
2011-00-22
Pages
38703-38713
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC3207479
Subset
IM
Grants
Intramural NIH HHS · ZIA ES090057 · United States
External Links
PubMed source DOI: 10.1074/jbc.M111.275370 PMC Full Text View journal details
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