Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis

被引:35
作者
Cakmak, Hakan
Basar, Murat [2 ]
Seval-Celik, Yasemin
Osteen, Kevin G. [3 ]
Duleba, Antoni J. [4 ]
Taylor, Hugh S.
Lockwood, Charles J.
Arici, Aydin [1 ]
机构
[1] Yale Univ, Sch Med, Sect Reprod Endocrinol & Infertil, Dept Obstet Gynecol & Reprod Sci, New Haven, CT 06520 USA
[2] Istanbul Univ, Dept Histol & Embryol, Cerrahpasa Med Sch, Istanbul, Turkey
[3] Vanderbilt Univ, Sch Med, Dept Obstet & Gynecol, Womens Reprod Hlth Res Ctr, Nashville, TN 37212 USA
[4] Univ Calif Davis, Dept Obstet & Gynecol, Sacramento, CA 95817 USA
关键词
endometriosis; statin; MCP-1; inflammation; SIMVASTATIN INDUCES APOPTOSIS; STROMAL CELLS; IN-VITRO; RHEUMATOID-ARTHRITIS; PERITONEAL-FLUID; ATORVASTATIN; WOMEN; MODEL; INTERLEUKIN-1-BETA; IMMUNOMODULATION;
D O I
10.1177/1933719111430998
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Statins are potent inhibitors of the endogenous mevalonate pathway. Besides inhibiting cholesterol biosynthesis, statins may also demonstrate anti-inflammatory properties. Inflammation is implicated in the attachment and invasion of endometrial cells to the peritoneal surface and growth of ectopic endometrium by inducing proliferation and angiogenesis. In this study, the effect of statins on monocyte chemotactic protein 1 (MCP-1) expression in endometriotic implants in nude mouse model and in cultured endometriotic cells was evaluated. In mouse model, simvastatin decreased MCP-1 expression in a dose-dependent manner in endometriotic implants (P < .05). Similarly, both simvastatin and mevastatin revealed a dose-dependent inhibition of MCP-1 production in cultured endometriotic cells (P < .01). This inhibitory effect of the statins on MCP-1 production was reversed by the downstream substrates of the mevalonate pathway. Moreover, statins decreased MCP-1 messenger RNA expression in cultured endometriotic cells (P < .05). In conclusion, statins exert anti-inflammatory effect in endometriotic cells and could provide a potential treatment of endometriosis in the future.
引用
收藏
页码:572 / 579
页数:8
相关论文
共 40 条
[1]   Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin [J].
Aktas, O ;
Waiczies, S ;
Smorodchenko, A ;
Dörr, J ;
Seeger, B ;
Prozorovski, T ;
Sallach, S ;
Endres, M ;
Brocke, S ;
Nitsch, R ;
Zipp, F .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (06) :725-733
[2]   Monocyte chemotactic protein-1 concentration in peritoneal fluid of women with endometriosis and its modulation of expression in mesothelial cells [J].
Arici, A ;
Oral, E ;
Attar, E ;
Tazuke, SI ;
Olive, DL .
FERTILITY AND STERILITY, 1997, 67 (06) :1065-1072
[3]   REGULATION OF INTERLEUKIN-8 GENE-EXPRESSION IN HUMAN ENDOMETRIAL CELLS IN CULTURE [J].
ARICI, A ;
HEAD, JR ;
MACDONALD, PC ;
CASEY, ML .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1993, 94 (02) :195-204
[4]   Atorvastatin impairs the myocardial angiogenic response to chronic ischemia in normocholesterolemic swine [J].
Boodhwani, Munir ;
Mieno, Shigetoshi ;
Feng, Jun ;
Sodha, Neel R. ;
Clements, Richard T. ;
Xu, Shu-Hua ;
Sellke, Frank W. .
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 2008, 135 (01) :117-122
[5]   Simvastatin Protects against the Development of Endometriosis in a Nude Mouse Model [J].
Bruner-Tran, Kaylon L. ;
Osteen, Kevin G. ;
Duleba, Antoni J. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 94 (07) :2489-2494
[6]   Down-regulation of endometrial matrix metalloproteinase-3 and -7 expression in vitro and therapeutic regression of experimental endometriosis in vivo by a novel nonsteroidal progesterone receptor agonist, tanaproget [J].
Bruner-Tran, KL ;
Zhang, ZM ;
Eisenberg, E ;
Winneker, RC ;
Osteen, KG .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2006, 91 (04) :1554-1560
[7]  
Cakmak Hakan, 2009, Front Biosci (Elite Ed), V1, P429
[8]   Simvastatin induces apoptosis in human colon cancer cells and in tumor xenografts, and attenuates colitis-associated colon cancer in mice [J].
Cho, Soo-Jeong ;
Kim, Joo Sung ;
Kim, Jung Mogg ;
Lee, Jong Yeul ;
Jung, Hyun Chae ;
Song, In Sung .
INTERNATIONAL JOURNAL OF CANCER, 2008, 123 (04) :951-957
[9]   Immunomodulation by statins: mechanisms and potential impact on autoimmune diseases [J].
Chow, Sek C. .
ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS, 2009, 57 (04) :243-251
[10]   Apoptosis in endometrial glandular and stromal cells in women with and without endometriosis [J].
Dmowski, WP ;
Ding, J ;
Shen, J ;
Rana, N ;
Fernandez, BB ;
Braun, DP .
HUMAN REPRODUCTION, 2001, 16 (09) :1802-1808