Glucocorticoid upregulation of the annexin-A1 receptor in leukocytes.
We tested here whether glucocorticoids modulated myeloid cell expression of a specific G-coupled receptor, termed formyl-peptide receptor like-1 (FPRL-1), recently shown to mediate the anti-inflammatory actions of annexin-A1. Real-time PCR and flow cytometry demonstrated rapid up-regulation of mRNA followed by the protein in HL-60 cells incubated with dexamethasone, with peaks at 2 and 24h, respectively. This effect was not restricted to dexamethasone, since reproduced by glucocorticoids. In addition, it was not restricted to the cell line, since replicated with human peripheral blood monocytes. Glucocorticoid ability to upregulate cell surface expression of FPRL-1 was specific, since no effects upon the related receptor FPR or the integrin CD11b could be detected. In view of the wide range of endogenous ligands known to interact with FPRL-1, including the anti-inflammatory protein annexin-A1, we speculate that the novel effect here described may impact on the clinical immunosuppressive and anti-inflammatory properties of glucocorticoids.
Sawmynaden
Prescilla
P
The William Harvey Research Institute, Bart's and the London, Charterhouse Square, London EC1M 6BQ, UK.
Perretti
Mauro
M
D017305:Annexin A1 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000008:administration & dosage*; D018922:HL-60 Cells; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism*; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D017305:Annexin A1; C105101:FPR2 protein, human; D005938:Glucocorticoids; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide; C515222:annexin-A1 receptor, human