Steroid hormones differentially regulate expression of complement receptors immunoglobulin in human macrophages, involving the glucocorticoid receptor

We have previously reported that the glucocorticoid, dexamethasone, increases the expression of Complement Receptor Immunoglobulin (CRIg) in macrophages. Since the sex steroid hormones, progesterone, estradiol and testosterone also affect macrophages functions, it was of interest to see if these also modulated CRIg expression in macrophages and whether, the steroids effect these changes through the glucocorticoid receptor (GR). The data showed that only progesterone and dexamethasone increased CRIg expression in human monocyte-derived macrophages (MDM). The other two steroids had no effect on the expression of this receptor at both the mRNA and protein level. Western blot analysis revealed that this was the case for both spliced forms of CRIg, the long (L) and short (S) isoforms. However, all four steroids had no effect on the expression of CR1 (CD35) and CR3 (CD11b) but caused an increase in CR4 (CD11c) expression. Interestingly the effects of dexamethasone and progesterone correlated with their ability to induced expression of the GR and an increase in its nuclear translocation. The importance of the GR in regulating the steroid-induced increase in CRIg expression, was demonstrated by the finding that knocking down the levels of GR using shRNA, led to a loss of the dexamethasone-induced up regulation of CRIg expression. The increase in CRIg expression by dexamethasone and progesterone was also evident in cell surface expression of the receptor, assessed by flow cytometry. Our findings reveal that the steroids differ in their effects on macrophage CRIg expression and that they have different effects on the expression of the different complement receptors. The expression of CRIg including its up-regulation by steroids requires the GR. *Correspondence to: Kanchana Usuwanthim, Cellular and Molecular Immunology Research Unit, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand, E-mail: kanchanau@nu.ac.th