title: Progesterone reduces the migration of mast cells toward the chemokine stromal cell-derived factor-1/CXCL12 with an accompanying decrease in CXCR4 receptors.
abstract: Mast cell recruitment is implicated in many physiological functions and several diseases. It depends on microenvironmental factors, including hormones. We have investigated the effect of progesterone on the migration of HMC-1(560) mast cells toward CXCL12, a chemokine that controls the migration of mast cells into tissues. HMC-1(560) mast cells were incubated with 1 nM to 1 microM progesterone for 24 h. Controls were run without progesterone. Cell migration toward CXCL12 was monitored with an in vitro assay, and statistical analysis of repeated experiments revealed that progesterone significantly reduced cell migration without increasing the number of apoptotic cells (P = 0.0084, n = 7). Differences between progesterone-treated and untreated cells were significant at 1 microM (P < 0.01, n = 7). Cells incubated with 1 microM progesterone showed no rearrangment of actin filaments in response to CXCL12. Progesterone also reduced the calcium response to CXCL12 and Akt phosphorylation. Cells incubated with progesterone had one-half the control concentrations of CXCR4 (mRNA, total protein, and membrane-bound protein). Progesterone also inhibited the migration of HMC-1(560) cells transfected with hPR-B-pSG5 plasmid, which contained 2.5 times as much PR-B as the control. These transfected cells responded differently (P < 0.05, n = 5) from untreated cells to 1 nM progesterone. We conclude that progesterone reduces mast cell migration toward CXCL12 and that CXCR4 may be a progesterone target in mast cells.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Univ Paris-Sud 11, Institut Fédératif de Recherche 13, Assistance Publique-Hôpitaux de Paris, Hôpital Antoine Béclère, Service de Microbiologie-Immunologie Biologique, Clamart, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Belot
authors.forename: Latifa
authors.initials: L
authors.lastname: Abdennebi-Najar
authors.forename: Françoise
authors.initials: F
authors.lastname: Gaudin
authors.forename: Michèle
authors.initials: M
authors.lastname: Lieberherr
authors.forename: Véronique
authors.initials: V
authors.lastname: Godot
authors.forename: Joelle
authors.initials: J
authors.lastname: Taïeb
authors.forename: Dominique
authors.initials: D
authors.lastname: Emilie
authors.forename: Véronique
authors.initials: V
authors.lastname: Machelon
mesh_terms: D000199:Actins / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077191:Wortmannin
chemical_list: D000199:Actins; D000730:Androstadienes; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D011980:Receptors, Progesterone; C097314:progesterone receptor B; D011374:Progesterone; D051058:Oncogene Protein v-akt; D002118:Calcium; D000077191:Wortmannin