Interleukin-4 stimulates proliferation of endometriotic stromal cells.
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.
OuYang
Zhuo
Z
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Hirota
Yasushi
Y
Osuga
Yutaka
Y
Hamasaki
Kahori
K
Hasegawa
Akiko
A
Tajima
Toshiki
T
Hirata
Tetsuya
T
Koga
Kaori
K
Yoshino
Osamu
O
Harada
Miyuki
M
Takemura
Yuri
Y
Nose
Emi
E
Yano
Tetsu
T
Taketani
Yuji
Y
D000328:Adult; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000473:pathology*; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D017154:Stromal Cells / Q000502:physiology
D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D020929:Mitogen-Activated Protein Kinase Kinases; D001973:Bromodeoxyuridine