CXCR4 expression on monocytes is up-regulated by dexamethasone and is modulated by autologous CD3+ T cells.
Chemokines and their receptors regulate cell migration to sites of inflammation. The glucocorticoid dexamethasone has potent anti-inflammatory effects, yet paradoxically up-regulates expression of some cytokine receptors. We have examined the effects of dexamethasone on chemokine receptor expression. Using an RNase protection assay, we show that dexamethasone up-regulates human peripheral blood mononuclear cell (PBMC) expression of CXCR4 mRNA. Flow cytometric analysis demonstrated that increased expression of CXCR4, but not CXCR1 and CXCR2, occurred on both monocytes and CD3+ T cells in PBMC mixed cultures. A stromal-derived factor (SDF)-1alpha-mediated calcium influx was detected on monocytes. Basal levels of CXCR4 expression on purified monocytes were lower when compared with monocytes in mixed PBMC cultures. Co-culture of monocytes with purified CD3+ T cells led to enhanced basal expression of CXCR4 on monocytes. The use of transwells to partition CD3+ T cells resulted in increased CXCR4 expression on monocytes, suggesting that CD3+ T-cell derived soluble factors regulate CXCR4 expression.
Caulfield
Jason
J
Department of Respiratory Medicine & Allergy, Guy's Hospital, London SE1 9RT, UK. catherine.hawrylowicz@kcl.ac.uk
Fernandez
Maria
M
Snetkov
Vladimir
V
Lee
Tak
T
Hawrylowicz
Catherine
C
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001685:Biological Factors / Q000502:physiology; D017252:CD3 Complex / Q000032:analysis; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D019718:Receptors, CXCR4 / Q000097:blood / Q000187:drug effects* / Q000235:genetics; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D001685:Biological Factors; D017252:CD3 Complex; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D005938:Glucocorticoids; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D003907:Dexamethasone