Endometriosis Knowledgebase


A repository for genes associated with endometriosis

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PMID 18599603
Gene Name IL4
Condition Endometriosis
Association Associated
Sex Female
Associated genes IL-4
Other associated phenotypes Endometriosis
Interleukin-4 stimulates proliferation of endometriotic stromal cells.

Am J Pathol. 2008 Aug;173(2):463-9. doi: 10.2353/ajpath.2008.071044. Epub 2008

OuYang, Zhuo| Hirota, Yasushi| Osuga, Yutaka| Hamasaki, Kahori| Hasegawa, Akiko| Tajima, Toshiki| Hirata, Tetsuya| Koga, Kaori| Yoshino, Osamu| Harada, Miyuki| Takemura, Yuri| Nose, Emi| Yano, Tetsu| Taketani, Yuji

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Several lines of evidence indicate that the Th2 immune response is associated with endometriosis. Although an increased concentration of interleukin (IL)-4, a typical Th2 cytokine, has been reported in endometriotic tissues, the implication of this for endometriosis has not been determined. To investigate a possible role of IL-4 in the development of endometriosis, we examined the presence of IL-4-producing cells in endometriotic tissues and the effect of IL-4 on proliferation of endometriotic stromal cells. Endometriotic stromal cells were isolated from endometriotic tissues obtained from women undergoing surgery for endometrioma. Immunohistochemistry of endometriotic tissues revealed that IL-4-positive cells were abundant in the stroma. The effect of IL-4 on proliferation of endometriotic stromal cells was studied using cell counting and BrdU incorporation assays. IL-4 (0.1 to 10 ng/ml) significantly increased cell number and BrdU incorporation in a dose-dependent manner, and the proliferative effect of IL-4 was inhibited by anti-IL-4 receptor antibody. IL-4-induced activation of mitogen-activated protein kinases in endometriotic stromal cells was examined by Western blotting. IL-4 induced phosphorylation of p38 mitogen-activated protein kinase, stress-activated protein kinase/c-Jun kinase, and p42/44 mitogen-activated protein kinase and inhibitors of these kinases suppressed IL-4-induced proliferation of endometriotic stromal cells. These findings suggest that proliferation of endometriotic stromal cells induced by locally produced IL-4 is involved in the development of endometriosis.

Mesh Terms: Adult| Bromodeoxyuridine| *Cell Proliferation| Endometriosis/*metabolism/pathology| Endometrium/*pathology| Female| Humans| Interleukin-4/*physiology| Mitogen-Activated Protein Kinase Kinases/physiology| Receptors, Interleukin-4/metabolism| Stro