title: The effect of progesterone on genes involved in preterm labor.
abstract: The decidua is known to be a major source of intrauterine PGF2α during late gestation and labor, and inflammatory cytokines, including IL-1β, IL-6, and IL-8, are elevated in spontaneous preterm deliveries. In the present study, to elucidate how progesterone blocks the pathways associated with preterm birth, we determined the effects of P4 on the expression of PTGS-2 and PTGFR mRNA in human decidua fibroblast cells, as well as the genes, using microarray analysis. Senescence was induced in primary cultured human decidual cells treated with IL-1β. The IL-1β treatment implicated by microarray analysis increased gene expression levels of PTGS-2, PTGFR, NFκ-B p65, IL-17, and IL-8. In contrast, P4+IL-1β decreased the expression levels of all of these genes in comparison to treatment with IL-1β alone (p<0.05). IL-1β also increased the proportion of SA-β-gal-positive cells. Treatment with IL-1β also increased the p21 protein level in comparison to cells treated either with the vehicle or P4. Neither the p21 protein level nor the number of SA-β-gal-positive cells was increased in normal endometrial glandular cells by IL-1β (p<0.05). Our studies demonstrated that P4 changes the level of gene expression in a manner that favors an anti-inflammatory milieu. Because IL-8 appears to be the cytokine whose expression is most significantly modulated by P4, further studies evaluating IL-8 as a therapeutic target are needed.
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Okabe
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan. Electronic address: shintaro@juntendo.ac.jp.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Makino
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kato
authors.affiliation: Center for Maternal, Fetal and Neonatal Medicine, Saitama Medical Center, Saitama, Japan.
authors.forename: Kikumi
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Center for Maternal, Fetal and Neonatal Medicine, Saitama Medical Center, Saitama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Seki
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000328:Adult; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004717:Endometrium / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007752:Obstetric Labor, Premature / Q000097:blood* / Q000276:immunology; D011247:Pregnancy; D011374:Progesterone / Q000097:blood* / Q000276:immunology; D011982:Receptors, Prostaglandin / Q000096:biosynthesis* / Q000276:immunology; D051996:Transcription Factor RelA / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D016207:Cytokines; C498143:RELA protein, human; D011982:Receptors, Prostaglandin; D051996:Transcription Factor RelA; C034671:prostaglandin F2alpha receptor; D011374:Progesterone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: IL-1β; IL-8; NFκ-B p65; P4; p21