[Frontiers in Bioscience E3, 591-603, January 1, 2011]

The role of nuclear factor-kappa-B p50 subunit in the development of endometriosis

Yuan Lu1, Qunyan Sun2, Yu Zheng1, Xishi Liu1, Jian-Guo Geng3, Sun-Wei Guo1

1Shanghai OB/GYN Hospital, Fudan University, Shanghai, China 200011,2Dept. of Obstetrics and Gynecology, Cixi People's Hospital, Cixi, Zhejiang, China 315300,3Vascular Biology Center and Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Animals
3.2. Experiment protocol
3.3. Surgical procedures
3.4. Immunohistochemistry
3.5. Statistical analysis
4. Results
4.1. The growth of ectopic endometrial implants in different groups
4.2. Immunoreactivity to p-p65, PKCepsilon, and TRPV1 in ectopic endometrium
4.3. Immunoreactivity to p-p65, PKCepsilon and TRPV1 in eutopic endometrium
4.4. Immunoreactivity to p-p65, PKCepsilon and TRPV1 in vagina
5. Discussion
6. Acknowledgment
7. References

1. ABSTRACT

p50 is a member of the NF-kappaB family known to be involved in endometriosis. To gain insight into the roles of p50 in the development of endometriosis, we cross-transplanted endometrial fragments from p50 knockout mice to wild-type mice and vice versa, and also autotransplanted the fragments within the knockout and wild-type mice, inducing endometriosis. We then evaluated the size of the endometrial implants, and immunoreactivity to phosphorylated p65 (p-p65), PKCepsilon and TRPV1 in ectopic and eutopic endometrium as well as in vagina. We found that p50 deletion significantly reduces the size of endometrial implants. The immunoreactivity to p-p65 and PKCepsilon, but not TRPV1, was reduced in endometrial implants in p50 knockout mice. Deletion of p50 significantly reduced p-p65 and PKCepsilon, but not TRPV1, expression in eutopic endometrium and vagina. It also disrupts NF-kappaB activation and PKCepsilon expression in eutopic and vagina, suggesting the role of NF-kappaB in regulating PKCepsilon, which plays an important role in nociception. These data show that p50 is involved in the development of endometriosis and may be a promising therapeutic target.