TY - JOUR
T1 - Changing glucocorticoid action
T2 - 11β-Hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation
AU - Chapman, Karen E.
AU - Coutinho, Agnes E.
AU - Zhang, Zhenguang
AU - Kipari, Tiina M J
AU - Savill, John S.
AU - Seckl, Jonathan R.
PY - 2013
Y1 - 2013
N2 - Since the discovery of cortisone in the 1940s and its early success in treatment of rheumatoid arthritis, glucocorticoids have remained the mainstay of anti-inflammatory therapies. However, cortisone itself is intrinsically inert. To be effective, it requires conversion to cortisol, the active glucocorticoid, by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Despite the identification of 11β-HSD in liver in 1953 (which we now know to be 11β-HSD1), its physiological role has been little explored until recently. Over the past decade, however, it has become apparent that 11β-HSD1 plays an important role in shaping endogenous glucocorticoid action. Acute inflammation is more severe with 11β-HSD1-deficiency or inhibition, yet in some inflammatory settings such as obesity or diabetes, 11β-HSD1-deficiency/inhibition is beneficial, reducing inflammation. Current evidence suggests both beneficial and detrimental effects may result from 11β-HSD1 inhibition in chronic inflammatory disease. Here we review recent evidence pertaining to the role of 11β-HSD1 in inflammation. This article is part of a Special Issue entitled 'CSR 2013'.
AB - Since the discovery of cortisone in the 1940s and its early success in treatment of rheumatoid arthritis, glucocorticoids have remained the mainstay of anti-inflammatory therapies. However, cortisone itself is intrinsically inert. To be effective, it requires conversion to cortisol, the active glucocorticoid, by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Despite the identification of 11β-HSD in liver in 1953 (which we now know to be 11β-HSD1), its physiological role has been little explored until recently. Over the past decade, however, it has become apparent that 11β-HSD1 plays an important role in shaping endogenous glucocorticoid action. Acute inflammation is more severe with 11β-HSD1-deficiency or inhibition, yet in some inflammatory settings such as obesity or diabetes, 11β-HSD1-deficiency/inhibition is beneficial, reducing inflammation. Current evidence suggests both beneficial and detrimental effects may result from 11β-HSD1 inhibition in chronic inflammatory disease. Here we review recent evidence pertaining to the role of 11β-HSD1 in inflammation. This article is part of a Special Issue entitled 'CSR 2013'.
KW - 11β-Hydroxysteroid dehydrogenase
KW - Arthritis
KW - Glucocorticoid
KW - Inflammation
KW - Macrophage
KW - Mineralocorticoid
UR - http://www.scopus.com/inward/record.url?scp=84886585499&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2013.02.002
DO - 10.1016/j.jsbmb.2013.02.002
M3 - Review article
C2 - 23435016
AN - SCOPUS:84886585499
SN - 0960-0760
VL - 137
SP - 82
EP - 92
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
ER -