PMID- 1991073
OWN - NLM
STAT- MEDLINE
DCOM- 19910308
LR  - 20131121
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 4
IP  - 2
DP  - 1991 Feb
TI  - Potential regulation of inflammation in the lung by local metabolism of 
      hydrocortisone.
PG  - 166-73
AB  - Human lung tissue converts hydrocortisone to cortisone by the action of the 
      enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). Since cortisone is 
      inactive as an antiinflammatory steroid, the action of this enzyme may regulate 
      the local antiinflammatory effects of glucocorticoids in the lung. Minced human 
      lung tissue (100 mg in 500 microliters medium) metabolized approximately 50% of 
      added [3H]hydrocortisone within 2 h in most lung specimens. Metabolism was linear 
      during this period and was found to occur over a broad range of concentrations of 
      hydrocortisone (1 to 1,000 nM). Metabolism of hydrocortisone was not observed in 
      minced pulmonary blood vessels or airways (2 to 3 mm), and pleura (containing 
      some adherent parenchyma) had less activity than parenchyma. Cultured human 
      tracheal epithelial cells metabolized hydrocortisone, while umbilical vein 
      endothelial cells did not. Since glycyrrhizin, glycyrrhetinic acid, and 
      carbenoxolone have antiinflammatory properties and have recently been shown to 
      interfere with steroid metabolism in renal tissues, their effects on 11 beta-HSD 
      in human lung tissue have been tested. Conversion of hydrocortisone to cortisone 
      by lung tissue was inhibited by glycyrrhetinic acid (IC50, approximately 2.5 x 
      10(-8) M) and carbenoxolone (1.5 x 10(-7) M), but not glycyrrhizin (greater than 
      10(-5) M). It is proposed that inhibition of the metabolism of hydrocortisone by 
      11 beta-HSD may partially explain the known antiinflammatory actions of orally 
      administered glycyrrhetinic acid and carbenoxolone and that intrapulmonary 
      administration of these compounds may produce antiinflammatory effects targeted 
      to the lung.
FAU - Schleimer, R P
AU  - Schleimer RP
AD  - Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224.
LA  - eng
GR  - AI-20136/AI/NIAID NIH HHS/United States
GR  - AR-31891/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 6FO62043WK (Glycyrrhizic Acid)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - MM6384NG73 (Carbenoxolone)
RN  - P540XA09DR (Glycyrrhetinic Acid)
RN  - V27W9254FZ (Cortisone)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Carbenoxolone/pharmacology
MH  - Cells, Cultured
MH  - Cortisone/metabolism
MH  - Endothelium, Vascular/metabolism
MH  - Epithelium/metabolism/pathology
MH  - Glycyrrhetinic Acid/analogs & derivatives/pharmacology
MH  - Glycyrrhizic Acid
MH  - Humans
MH  - Hydrocortisone/*metabolism
MH  - Hydroxysteroid Dehydrogenases/metabolism
MH  - Inflammation/metabolism
MH  - Kinetics
MH  - Lung/blood supply/*metabolism
MH  - Pleura/metabolism
MH  - Trachea/metabolism
EDAT- 1991/02/01 00:00
MHDA- 1991/02/01 00:01
CRDT- 1991/02/01 00:00
PHST- 1991/02/01 00:00 [pubmed]
PHST- 1991/02/01 00:01 [medline]
PHST- 1991/02/01 00:00 [entrez]
AID - 10.1165/ajrcmb/4.2.166 [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 1991 Feb;4(2):166-73. doi: 10.1165/ajrcmb/4.2.166.