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Glucocorticoid regulated expression of the anti‐inflammatory receptor ALXR.
Author(s) -
Renshaw Derek,
Sawmynadan Prescilla,
Dalli Jesmond,
Perretti Mauro
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a645-c
Subject(s) - glucocorticoid receptor , receptor , gene expression , glucocorticoid , annexin a1 , endocrinology , medicine , cell culture , flow cytometry , transfection , cell , microbiology and biotechnology , chemistry , annexin , biology , gene , biochemistry , genetics
Glucocorticoids (GCs) are used at supra‐physiological doses to dampen unwanted immune responses. Annexin I (AnxA1) is a GC induced anti‐inflammatory protein, which mediates its effects through the lipoxin A4 receptor, also known as FPRL‐1 or ALXR. Our aim was to investigate whether glucocorticoids and AnxA1 were involved in the regulation of the ALXR receptor expression. The ‘neutrophil‐like cell’ line HL60’s were incubated with 0–1 mM dexamethasone (Dex). Dex showed a significant increase in ALXR mRNA expression at 2–16 h. The increase in ALXR gene expression was also translated to an increase in cell surface protein expression, as measured by flow cytometry following an overnight incubation with Dex. This was further shown to increase with both time (4–24 hr) and dose (0.1–1 mM). The experiments were repeated in PBMC were a similar increase in ALXR gene and protein expression was found. The time course of gene expression was more transient than in HL60s, with a maximum increase observed at 4 h and a return to basal levels by 24 h. The cell surface expression of ALXR was restricted to PMN and monocytes with no expression being detected on lymphocytes. An ALXR transfected HEK293 cell line was also used to investigate the involvement of the GC inducible protein AnxA1 on ALXR expression: an increase in ALXR mRNA and cell surface expression were measured at 4 h. These results indicate a selective modulatory action of anti‐inflammatory GC and AnxA1 on ALXR expression, thus expanding the potential functions of this receptor, perhaps even to clinical settings. Supported by the Arthritis Research Campaign UK (Fellowship 15755).