Inflammatory mediators down-regulate 11β-hydroxysteroid dehydrogenase type 2 in a human lung epithelial cell line BEAS-2B and the rat lung

Satoshi Suzuki, Hiroyoshi Tsubochi, Hironori Ishibashi, Yasushi Matsuda, Takashi Suzuki, Zygmunt S. Krozowski, Hironobu Sasano, Takashi Kondo

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

In the lung, anti-inflammatory actions of glucocorticoids would be determined by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), the microsomal enzyme responsible for the breakdown of bio-active glucocorticoids. However, regulation of 11β-HSD2 under inflammatory conditions such as acute lung injury is not well understood. In the present study, we examined whether inflammatory substances would influence the activity and mRNA expression of 11β-HSD2 in the lung. In a human bronchial epithelial cell line BEAS-2B, endotoxin inhibited 11β-HSD2 enzyme activity in a dose-dependent manner over 48 h with a significant decrease in the mRNA expression. Likewise, tumor necrosis factor (TNF)-α inhibited both activity and mRNA expression of 11β-HSD2. The TNF-α-dependent decrease in the enzyme activity was completely blocked by anti-TNF-α antibody, while antibody alone showed no significant influence on the enzyme activity. An nitric oxide donor (NO) sodium nitropusside or a cGMP analog 8-br-cGW caused moderate but significant decreases in both activity and mRNA expression of 11β-HSD2. Importantly, treatment of rats with endotoxin significantly decreased both activity and mRNA expression of 11β-HSD2 in the lung tissue. We conclude that lung inflammation reduces local glucocorticoid breakdown and augments glucocorticoid action in the lung by down-regulating 11β-HSD2 via multiple mechanisms.

Original languageEnglish
Pages (from-to)293-301
Number of pages9
JournalTohoku Journal of Experimental Medicine
Volume207
Issue number4
DOIs
Publication statusPublished - 2005 Nov 4

Keywords

  • 11β-hydroxysteroid dehydrogenase type 2
  • Acute lung injury
  • Endotoxin
  • Glucocorticoids
  • Inflammation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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