title: Signal regulatory protein alpha1 is involved in the inhibitory effect of glucocorticoid receptor on the proliferation of murine macrophage RAW264.7 cell and mouse peritoneal macrophage.
abstract: Glucocorticoid (GC) effectively suppresses immune and inflammatory responses and inhibits the growth of several types of cells, but the role of GC and its receptor on macrophage proliferation is unclear. In our previous work, we found RAW-GR(-) cells (murine macrophage RAW264.7 cells stably transfected with GR-siRNA expression vector by RNA interference) grew faster by about twofold. In this study, we further explored the role and mechanisms of GC/GR on the proliferation of macrophage. We found that the growth of RAW264.7 cells was inhibited by dexamethasone (Dex) in a concentration-dependent manner. The mRNA and protein levels of signal regulatory protein alpha1 (SIRPA) were induced by GC/GR in RAW264.7 cells and SIRPA expression was decreased remarkably in RAW-GR(-) cells. Overexpression of SIRPA negatively regulated the proliferation of RAW-GR(-) cells, and inhibition of SIRPA expression by a small from RNA interference attenuated Dex-induced proliferation inhibition in RAW264.7 cells. The proliferation inhibition of GC/GR was also found in mouse peritoneal macrophage, which was associated with the increase in SIRPA induced by GC/GR as well. In addition, elevation of the expression of CDK2, cyclinD1, and cyclinB1, but not phosphorylated ERK1/2 and p38, was found in RAW-GR(-) cells. In conclusion, we provided the novel evidences that GC/GR inhibited the growth of RAW264.7 cells and mouse peritoneal macrophage, and the antiproliferative effect of GC/GR on these cells was at least in part a result from GC/GR-induced SIRPA expression. Up-regulation of CDK2, cyclinD1, and cyclinB1 was also related to the increased proliferation of RAW-GR(-) cells.
authors: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
authors: Xiaohui
authors: X
authors: Wang
authors: Yidong
authors: Y
authors: Li
authors: Xiaoyan
authors: X
authors: Zhu
authors: Yan
authors: Y
authors: Wang
authors: Fei
authors: F
authors: Diao
authors: Jian
authors: J
authors: Lu
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D056744:Cyclin B1; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000502:physiology*; D051379:Mice; D034622:RNA Interference; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C534700:Ccnb1 protein, mouse; D019926:Cyclin B; D056744:Cyclin B1; D005938:Glucocorticoids; C501922:Sirpa protein, mouse; D011965:Receptors, Glucocorticoid; D011971:Receptors, Immunologic; D019938:Cyclin D1; D003907:Dexamethasone; D051357:Cyclin-Dependent Kinase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases