Upregulation of 11β-hydroxysteroid dehydrogenase 1 in lymphoid organs during inflammation in the rat

Ergang, Peter; Vytáčková, Kateřina; Švec, Jiří; Bryndová, Jana; Mikšı́k, Ivan; Pácha, Jiřı́

doi:10.1016/j.jsbmb.2011.04.002

Cited by 22 publications

(23 citation statements)

References 42 publications

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“…Interestingly, the 11␤-HSD1 increase in patients with inflammatory bowel disease is greater in men (664). The same reciprocal regulation of 11␤-HSD1 (increased) and 11␤-HSD2 (decreased) is seen in rat experimental models of colitis (96,184), with the increase in 11␤-HSD1 in colonic intraepithelial lymphocytes consistent with migration of activated lymphocytes from the inflamed colon to mesenteric lymph nodes and spleen (184,186). Mouse models of inflammatory bowel disease also show increased 11␤-HSD1 in intestinal intraepithelial lymphocytes and mesenteric lymph nodes, but 11␤-HSD2 is unchanged (724).…”

Section: The Gastrointestinal Tract and Inflammatory Bowel Diseasementioning

confidence: 75%

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11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Chapman

Holmes

Seckl

2013

Physiological Reviews

707

601

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Glucocorticoid action on target tissues is determined by the density of “nuclear” receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental “programming.” The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues.

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Section: The Gastrointestinal Tract and Inflammatory Bowel Diseasementioning

confidence: 75%

“…These effects are replicated by TNF-␣ in colonic tissue explants (186). Interestingly, the 11␤-HSD1 increase in patients with inflammatory bowel disease is greater in men (664).…”

Section: The Gastrointestinal Tract and Inflammatory Bowel Diseasementioning

confidence: 89%

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Chapman

Holmes

Seckl

2013

Physiological Reviews

707

601

View full text Add to dashboard Cite

show abstract

“…[35]). So far, studies in inflammatory bowel disease have gone little beyond observation, though they do suggest that at least some of the increase in 11β-HSD1 expression occurs in activated lymphocytes that migrate from the inflamed colon to the draining lymph nodes [54]. Studies in human patients with rheumatoid arthritis suggest differential regulation of 11β-HSDs in immune and mesenchymal cells.…”

Section: Introductionmentioning

confidence: 99%

Changing glucocorticoid action: 11β-Hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation

Chapman

Coutinho

Zhang

et al. 2013

The Journal of Steroid Biochemistry and Molecular Biology

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“…11β-HSD1 is expressed in synovial macrophages and fibroblasts of patients with rheumatoid arthritis and is highly induced by the proinflammatory cytokines IL-1 and TNF-α in the latter cell type (13). Moreover, 11β-HSD1 is induced in cells recruited into the peritoneum during sterile peritonitis (9) and is increased in intestine in both human and rodent colitis (14, 15). Macrophages from mice deficient in 11β-HSD1 show delayed acquisition of phagocytic capacity and exaggerated production of IL-6 and other cytokines after activation with lipopolysaccharide (9, 16).…”

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confidence: 99%

11β-Hydroxysteroid Dehydrogenase Type 1, But Not Type 2, Deficiency Worsens Acute Inflammation and Experimental Arthritis in Mice

et al. 2012

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Glucocorticoids profoundly influence immune responses, and synthetic glucocorticoids are widely used clinically for their potent antiinflammatory effects. Endogenous glucocorticoid action is modulated by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). In vivo, 11β-HSD1 catalyzes the reduction of inactive cortisone or 11-dehydrocorticosterone into active cortisol or corticosterone, respectively, thereby increasing intracellular glucocorticoid levels. 11β-HSD2 catalyzes the reverse reaction, inactivating intracellular glucocorticoids. Both enzymes have been postulated to modulate inflammatory responses. In the K/BxN serum transfer model of arthritis, 11β-HSD1-deficient mice showed earlier onset and slower resolution of inflammation than wild-type controls, with greater exostoses in periarticular bone and, uniquely, ganglion cysts, consistent with greater inflammation. In contrast, K/BxN serum arthritis was unaffected by 11β-HSD2 deficiency. In a distinct model of inflammation, thioglycollate-induced sterile peritonitis, 11β-HSD1-deficient mice had more inflammatory cells in the peritoneum, but again 11β-HSD2-deficient mice did not differ from controls. Additionally, compared with control mice, 11β-HSD1-deficient mice showed greater numbers of inflammatory cells in pleural lavages in carrageenan-induced pleurisy with lung pathology consistent with slower resolution. These data suggest that 11β-HSD1 limits acute inflammation. In contrast, 11β-HSD2 plays no role in acute inflammatory responses in mice. Regulation of local 11β-HSD1 expression and/or delivery of substrate may afford a novel approach for antiinflammatory therapy.

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Upregulation of 11β-hydroxysteroid dehydrogenase 1 in lymphoid organs during inflammation in the rat

Cited by 22 publications

References 42 publications

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Changing glucocorticoid action: 11β-Hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation

11β-Hydroxysteroid Dehydrogenase Type 1, But Not Type 2, Deficiency Worsens Acute Inflammation and Experimental Arthritis in Mice

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