Glucocorticoid treatment inhibits annexin-1 expression in rheumatoid arthritis CD4+ T cells.
OBJECTIVE
Annexin-1 (Anx-A1) has been recently shown to play a key role in T-cell activation and to be highly expressed in T cells from RA patients. Here, we investigated the effects of glucocorticoids (GCs) on Anx-A1 expression in T cells in vitro and in vivo.


METHODS
To evaluate the effects of dexamethasone (Dex) on Anx-A1 expression, human peripheral blood T cells were incubated with Dex and then analysed by real-time PCR and western blotting. Similar experiments were carried out in vivo by measuring Anx-A1 levels in T cells from patients with RA before and after administration of steroids.


RESULTS
Incubation of T cells with Dex decreased Anx-A1 levels in a time-dependent fashion and almost abolished its expression after 12 h. Stimulation of T cells pre-incubated with Dex for 12 h with anti-CD3/CD28 led to significant reduction of IL-2 production. Addition of human recombinant Anx-A1 to Dex-treated cells reversed the inhibitory effects of the steroids on anti-CD3/CD28-induced IL-2 production. Treatment of RA patients with steroid decreased Anx-A1 expression in T cells.


CONCLUSIONS
GCs suppress Anx-A1 expression in T cells in vitro and in vivo. These results provide evidence for a novel pathway by which steroids regulate the adaptive immune response and suggest that Anx-A1 may represent a target for the treatment of autoimmune diseases.
D'Acquisto
F
F
The William Harvey Research Institute, Centre for Biochemical Pharmacology, Barts and The London, Queen Mary School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK. F.Dacquisto@qmul.ac.uk
Paschalidis
N
N
Raza
K
K
Buckley
C D
CD
Flower
R J
RJ
Perretti
M
M
D000368:Aged; D000369:Aged, 80 and over; D017305:Annexin A1 / Q000032:analysis* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D015153:Blotting, Western; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003864:Depression, Chemical; D003907:Dexamethasone / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017305:Annexin A1; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D005938:Glucocorticoids; D007376:Interleukin-2; D003907:Dexamethasone