title: Effects of 1,25-Dihydroxy Vitamin D3 on Endometriosis.
abstract: Endometriosis is an estrogen-dependent, chronic inflammatory disease. Recent studies have shown that vitamin D (VD) is an effective modulator of the immune system and plays an important role in controlling many inflammatory diseases.
  
  
  
  The objective of the study was to clarify the in vitro effects of 1,25-dihydroxy vitamin D3 (1,25[OH]2D3) on human endometriotic stromal cells (ESCs) and to determine the serum levels of VD in endometriosis patients.
  
  
  
  ESCs were isolated from ovarian endometrioma and cultured with 1,25(OH)2D3. Gene expression of IL-8, cyclooxygenase-2, microsomal prostaglandin E synthase-1, microsomal prostaglandin E synthase-2, cytosolic prostaglandin E synthase, 15-hydroxyprostaglandin dehydrogenase, matrix metalloproteinase (MMP)-2, and MMP-9 was examined using quantitative RT-PCR. The production of IL-8 and prostaglandin E2 was measured using an ELISA and an enzyme immunoassay. Viable cell number was assessed using a cell-counting assay, and DNA synthesis was assessed using the bromodeoxyuridine incorporation assay. Apoptosis was assessed using flow cytometry. The expression of inhibitory-κBα protein was detected using Western blotting. The serum levels of 25-hydroxyvitamin D3 and 1,25(OH)2D3 were measured by a RIA.
  
  
  
  In vitro studies showed that 1,25(OH)2D3 significantly reduced IL-1β- or TNF-α-induced inflammatory responses, such as IL-8 expression and prostaglandin activity. 1,25(OH)2D3 also reduced viable ESC numbers and DNA synthesis but did not affect apoptosis. MMP-2 and MMP-9 expressions were reduced by 1,25(OH)2D3. 1,25(OH)2D3 inhibited nuclear factor-κB activation. The serum 25-hydroxyvitamin D3 levels were significantly lower in women with severe endometriosis than in the controls and women with mild endometriosis. Serum 1,25(OH)2D3 levels were not different between groups.
  
  
  
  VD modulates inflammation and proliferation in endometriotic cells, and a lower VD status is associated with endometriosis. Taken together, VD supplementation could be a novel therapeutic strategy for managing endometriosis.
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Miyashita
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Koga
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Gentaro
authors.initials: G
authors.lastname: Izumi
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Fusako
authors.initials: F
authors.lastname: Sue
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Makabe
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Nagai
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Urata
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Takamura
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Harada
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hirata
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hirota
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Wada-Hiraike
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Osuga
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004715:Endometriosis / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D010049:Ovarian Diseases / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D000071876:Prostaglandin-E Synthases / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014807:Vitamin D / Q000097:blood*
chemical_list: D016209:Interleukin-8; D014807:Vitamin D; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D002117:Calcitriol