title: CXCR4 expression on monocytes is up-regulated by dexamethasone and is modulated by autologous CD3+ T cells.
abstract: 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.
authors.affiliation: Department of Respiratory Medicine & Allergy, Guy's Hospital, London SE1 9RT, UK. catherine.hawrylowicz@kcl.ac.uk
authors.forename: Jason
authors.initials: J
authors.lastname: Caulfield
authors.forename: Maria
authors.initials: M
authors.lastname: Fernandez
authors.forename: Vladimir
authors.initials: V
authors.lastname: Snetkov
authors.forename: Tak
authors.initials: T
authors.lastname: Lee
authors.forename: Catherine
authors.initials: C
authors.lastname: Hawrylowicz
mesh_terms: 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*
chemical_list: 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