Lipopolysaccharide Stress Induces Cryptic Exon Splice Variants of the Human Glucocorticoid Receptor

Tajia L. Green, Stacey M. Leventhal, Debora Lim, Kiho Cho, David G. Greenhalgh

Research output: Contribution to journalArticle

Abstract

Glucocorticoids are widely used in the treatment of numerous inflammatory conditions, including sepsis. Unfortunately, patient response to glucocorticoid therapy can be inconsistent. Variations in the human glucocorticoid receptor (hGR) may contribute to the differential patient response. We screened for hGR variants in the buffy coats of burn patients and peripheral blood mononuclear cells (PBMCs) treated with lipopolysaccharide. Three novel splice variants containing cryptic exons were upregulated in the PBMCs after lipopolysaccharide exposure at 3 and 13 h with the greatest observed expression at 3 h. Luciferase assays revealed that two of the isoforms had no significant activity in comparison with the reference hGR when stimulated with hydrocortisone. The third isoform had an augmented response that was greater than the reference hGR at a high cortisol dose. This shows that PBMCs are able to produce variant hGR isoforms in response to stress. Furthermore, lipopolysaccharide stress appears to induce these hGR variants, potentially by influencing mRNA splicing. In the future, identifying hGR expression profiles may be a key component in individually tailoring a patient's treatment to sepsis and injury.

Original languageEnglish (US)
Pages (from-to)590-597
Number of pages8
JournalShock (Augusta, Ga.)
Volume52
Issue number6
DOIs
StatePublished - Dec 1 2019

Fingerprint

Glucocorticoid Receptors
Lipopolysaccharides
Exons
Blood Cells
Protein Isoforms
Glucocorticoids
Hydrocortisone
Sepsis
Luciferases
Therapeutics
Messenger RNA
Wounds and Injuries

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Lipopolysaccharide Stress Induces Cryptic Exon Splice Variants of the Human Glucocorticoid Receptor. / Green, Tajia L.; Leventhal, Stacey M.; Lim, Debora; Cho, Kiho; Greenhalgh, David G.

In: Shock (Augusta, Ga.), Vol. 52, No. 6, 01.12.2019, p. 590-597.

Research output: Contribution to journalArticle

Green, Tajia L. ; Leventhal, Stacey M. ; Lim, Debora ; Cho, Kiho ; Greenhalgh, David G. / Lipopolysaccharide Stress Induces Cryptic Exon Splice Variants of the Human Glucocorticoid Receptor. In: Shock (Augusta, Ga.). 2019 ; Vol. 52, No. 6. pp. 590-597.
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