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: Kazuhiro Tamura, Haruka Takashima, Keiko Fumoto, Takeshi Kajihara, Satomi Uchino, Osamu Ishihara, Mikihiro Yoshie, Kazuya Kusama, Eiichi Tachikawa
• Journal: Reproductive sciences (Thousand Oaks, Calif.) (Reprod Sci) Vol. 22 Issue 9 Pg. 1088-97 (Sep 2015) ISSN: 1933-7205 [Electronic] United States
• PMID: 25667209 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2015.

Chemical References

• CXCL8 protein, human
• IL6 protein, human
• Interleukin-6
• Interleukin-8
• NF-kappa B
• Receptor, PAR-1
• Receptor, PAR-2
• SERPINA1 protein, human
• alpha 1-Antitrypsin
• Cyclooxygenase 2
• PTGS2 protein, human
• MTOR protein, human
• Proto-Oncogene Proteins c-akt
• Ribosomal Protein S6 Kinases, 70-kDa
• TOR Serine-Threonine Kinases

Topics

• Animals
• Cells, Cultured
• Cyclooxygenase 2 (metabolism)
• Disease Models, Animal
• Endometriosis (enzymology, genetics, pathology, prevention & control)
• Endometrium (enzymology, pathology, transplantation)
• Female
• Heterografts
• Humans
• Interleukin-6 (metabolism)
• Interleukin-8 (metabolism)
• Mice, Inbred BALB C
• Mice, Nude
• NF-kappa B (metabolism)
• Ovariectomy
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA Interference
• Receptor, PAR-1 (metabolism)
• Receptor, PAR-2 (metabolism)
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• Signal Transduction
• TOR Serine-Threonine Kinases (metabolism)
• Transfection
• alpha 1-Antitrypsin (genetics, metabolism)