The glucocorticoid inhibition of LFA-1 and CD2 expression by human mononuclear cells is reversed by IL-2, IL-7 and IL-15.
Glucocorticoids are agents endowed with powerful immunosuppressive and anti-inflammatory properties partially related to the inhibition of adhesion-related processes. We have previously demonstrated that glucocorticoids inhibit LFA-1 and CD2 expression in human peripheral blood mononuclear cells (PBMC) by down-regulating mRNA steady-state levels. In this study, we investigated whether glucocorticoids could also act indirectly by modulating the effect/function of cytokines whose expression are known to inhibit. To test this hypothesis, we replenished the following cytokines IL-2, IL-7, IL-15, TNF-alpha, IL-1beta, IL-4 and IL-10, in an in vitro PBMC culture system. Our results indicate that only the IL-2Rgamma-chain-dependent cytokines IL-2, IL-7 and IL-15, among the cytokines of this panel, could reverse the inhibition of glucocorticoids on PBMC adhesion molecule expression and the related functions of intercellular aggregation and proliferation. Furthermore, we also demonstrated that IL-2, IL-7 and IL-15 could induce de novo the synthesis of LFA-1 and CD2. Taken together, these data suggest that glucocorticoids inhibit PBMC LFA-1 and CD2 expression not only directly by modulating transcriptional events, but also indirectly through the inhibition of IL-2Rgamma-dependent cytokines.
Pipitone
N
N
Rheumatology Unit, Guy's, King's and St. Thomas's School of Medicine, Guy's Campus, London, GB, UK.
Sinha
M
M
Theodoridis
E
E
Goulding
N
N
Hall
M
M
Lanchbury
J
J
Corrigall
V
V
Panayi
G
G
Pitzalis
C
C
D018801:CD2 Antigens / Q000096:biosynthesis*; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004336:Drug Antagonism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015854:Up-Regulation
D018801:CD2 Antigens; D016207:Cytokines; D005938:Glucocorticoids; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7; D016169:Lymphocyte Function-Associated Antigen-1; D015375:Receptors, Interleukin-2; D003907:Dexamethasone