[Frontiers in Bioscience S4, 1213-1234, June 1, 2012]

The role of NF-kappaB in endometriosis

Apostolos Kaponis1, Tomio Iwabe2, Fuminori Taniguchi2, Masayuki Ito2, Imari Deura2, George Decavalas1, Naoki Terakawa2, Tasuku Harada2

1Department of Obstetrics and Gynecology, Patra University School of Medicine, Patra, Greece, 2Department of Obstetrics andGynecology, Tottori University Faculty of Medicine, Yonago, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. The NF-kappaB signaling pathway
4. Interactions between sex steroid hormones and NF-kappaB pathway
4.1. Progesterone and progesterone receptor
4.2. Estrogen receptor
5. NF-kappaB expression in normal endometrium
6. NF-kappaB expression in women with endometriosis
6.1. The role of NF-kappaB to promote inflammation in women with endometriosis
6.1.1. Cross-talk between NF-kappaB and cytokines in endometriosis. A positive auto-regulatory loop
6.1.2. NF-kappaB and macrophages
6.1.3. Interactions between NF-kappaB and progesterone receptor in endometriosis
6.1.4. NF-kappaB can regulate COX-2 and prostaglandin expression
6.2. NF-kappaB and angiogenesis
6.3. NF-kappaB and matrix metalloproteinases, plasminogen activator system
6.4. NF-kappaB and beta-catenin
6.5. NF-kappaB and oxidative stress
6.6. The two faces of NF-kappaB in apoptosis of endometriotic cells
7. The role of NF-kappaB in the treatment of endometriosis
7.1. Medical treatment for endometriosis affects the NF-kappaB pathway
7.2. Drugs mediating the NF-kappaB pathway affect also endometriosis progression
8. Conclusion and future perspectives
9. References

1. ABSTRACT

The nuclear factor kappaB (NF-kappaB) is a ubiquitously expressed transcription factor playing vital roles in innate immunity and other processes involving cellular survival, proliferation, and differentiation. This review highlights the importance of NF-kappaB in the pathophysiology of endometriosis. Constitutive activation of NF-kappaB has been shown in endometriotic lesions. Complex interactions of NF-kappaB with steroid receptors and apoptotic molecules in endometriosis resulting in opposing roles of NF-kappaB are discussed. NF-kappaB regulates the expression of cytokines mediating autocrine self-amplifying cycles of cytokine release and NF-kappaB activation, leading to maintenance of inflammatory reactions in endometriosis. NF-kappaB can contribute to the increased ability of endometriotic cells to invade and adhere to the peritoneal surface by regulating the expression of matrix metaloproteinases. We are presenting the role of NF-kappaB to regulate vascularization and oxidative stress in endometriotic cells. Effects of drugs used for the treatment of endometriosis on NF-kappaB pathway are presented and we show how drugs that inhibit the NF-kappaB can mediate the progression of endometriosis. Novel therapeutic strategies involving the NF-kappaB and applied in endometriosis are also discussed.