Increased IκB expression and diminished nuclear NF-κB in human mononuclear cells following hydrocortisone injection

A. Aljada, H. Ghanim, E. Assian, P. Mohanty, W. Hamouda, R. Garg, P. Dandona

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

We have recently demonstrated that hydrocortisone and other glucocorticoids inhibit reactive oxygen species (ROS) generation by mononuclear (MNC) and polymorphonuclear leucocytes (PMNL). Since NF-κB/IκB system regulates the transcription of proinflammatory genes, including those responsible for ROS generation, we tested the hypothesis that hydrocortisone may stimulate IκB production thus inhibiting NF-κB translocation from the cytosol into the nucleus in MNC, in vivo. One hundred milligram of hydrocortisone was injected intravenously into 4 normal subjects. Blood samples were obtained prior to the injection and at 1, 2, 4, 8 and 24 hr after the injection. Nuclear extracts and total cell lysates were prepared from MNC by standard techniques. IκB levels in MNC homogenates increased at 1 hr, peaked at 2-4 hr, started to decrease at 8 hr, and returned to baseline levels at 24 hr. NF-κB in MNC nuclear extracts decreased at 1 hr, reached a nadir at 4 hr, gradually increased at 8 hr and returned back to baseline levels at 24 hr. The total protein content of NF-κB subunit (P65) in MNC lysates also showed a decrease following hydrocortisone injection. This decrease was observed at 2 hr, reached a nadir at 4 hr, and returned to baseline levels at 24 hr. ROS generation inhibition paralleled NF-κB levels in the nucleus. It was inhibited at 1 hr, reached a nadir at 2-4 hr, started to increase at 8 hr, and returned to basal levels at 24 hr. Our data demonstrate that hydrocortisone induces IκB and suppresses NF-κB expression in MNC in parallel. IκB further reduces the translocation of NF-κB into the nucleus thus preventing the expression of proinflammatory genes.

Original languageEnglish (US)
Pages (from-to)3386-3389
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume84
Issue number9
DOIs
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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