title: Possible Role of α1-Antitrypsin in Endometriosis-Like Grafts From a Mouse Model of Endometriosis.
abstract: Previous study indicated that bleeding into the peritoneum may accelerate inflammatory response in endometriosis-like grafts in mice. To identify changes in protein levels in the grafts from mice that underwent unilateral ovariectomy (uOVX), which causes bleeding from ovarian arteries and vein, the grafts were generated by injecting a suspension of human endometrial cells in BALB/c nude female mice, and protein profile changes were compared with non-uOVX control mice. The level of α1-antitrypsin (α1-AT) decreased in grafts from nude mice that underwent uOVX. The levels of phosphorylated Akt, mammalian target of rapamycin, S6K, regulatory factors for cell survival, and of phosphorylated nuclear factor κB, an inflammatory mediator, were higher in endometriosis-like grafts from the uOVX group than from the control. The grafts were mostly comprised of stromal cells. The bioactivity of α1-AT was assessed by investigating cytokine expression in protease-activated receptor (PAR) 1/2 agonists-stimulated stromal cells. The PARs promoted the expression of interleukin 8 (IL-8), but treatment with α1-AT blocked IL-8 expression dose dependently. Knocking down α1-AT expression increased the constitutive IL-6, IL-8, and cyclooxygenase 2 expression as well as PAR1 agonist-stimulated IL-6 expression. These findings support the notion that decreased α1-AT protein in the grafts constituted with human endometrial cells in mice may have exacerbated inflammation in endometriosis-like grafts, suggesting the possible involvement of α1-AT in the pathophysiology of endometriosis.
authors: Department of Endocrine and Neural Pharmacology, Tokyo University of Pharmacy & Life Sciences, Hachioji, Tokyo, Japan hiro@toyaku.ac.jp.
authors: Kazuhiro
authors: K
authors: Tamura
authors: Department of Endocrine and Neural Pharmacology, Tokyo University of Pharmacy & Life Sciences, Hachioji, Tokyo, Japan.
authors: Haruka
authors: H
authors: Takashima
authors: Department of Endocrine and Neural Pharmacology, Tokyo University of Pharmacy & Life Sciences, Hachioji, Tokyo, Japan.
authors: Keiko
authors: K
authors: Fumoto
authors: Department of Obstetrics and Gynecology, Saitama Medical University, Saitama, Japan.
authors: Takeshi
authors: T
authors: Kajihara
authors: Department of Obstetrics and Gynecology, Saitama Medical University, Saitama, Japan.
authors: Satomi
authors: S
authors: Uchino
authors: Department of Obstetrics and Gynecology, Saitama Medical University, Saitama, Japan.
authors: Osamu
authors: O
authors: Ishihara
authors: Department of Endocrine and Neural Pharmacology, Tokyo University of Pharmacy & Life Sciences, Hachioji, Tokyo, Japan.
authors: Mikihiro
authors: M
authors: Yoshie
authors: Department of Endocrine and Neural Pharmacology, Tokyo University of Pharmacy & Life Sciences, Hachioji, Tokyo, Japan Present address: The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors: Kazuya
authors: K
authors: Kusama
authors: Department of Endocrine and Neural Pharmacology, Tokyo University of Pharmacy & Life Sciences, Hachioji, Tokyo, Japan.
authors: Eiichi
authors: E
authors: Tachikawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004715:Endometriosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D004717:Endometrium / Q000201:enzymology* / Q000473:pathology / Q000637:transplantation; D005260:Female; D064593:Heterografts; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D010052:Ovariectomy; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D044463:Receptor, PAR-1 / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014162:Transfection; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases
keywords: endometrial stromal cells; endometriosis; glandular epithelial cells; α1-antitrypsin