Interleukin-1β stimulates the secretion of thymic stromal lymphopoietin (TSLP) from endometrioma stromal cells: possible involvement of TSLP in endometriosis.
OBJECTIVE
Is thymic stromal lymphopoietin (TSLP) involved in the pathophysiology of endometriosis?


CONCLUSIONS
TSLP is up-regulated by interleukin (IL)-1β and may be involved in the development of endometriosis.


BACKGROUND
Endometriosis is a chronic inflammatory disease in which the Th2 immune response is activated and has been suggested to promote the disease. TSLP is a master cytokine that drive Th2 immune response.


METHODS
A laboratory study.


METHODS
Primary cultures of endometrioma stromal cells (ESCs) were treated with IL-1β, a typical inflammatory cytokine associated with endometriosis. Gene expression of TSLP in ESCs and secretion of TSLP protein from ESCs were studied using quantitative PCR and a specific ELISA. Interferon γ (IFNγ), a typical Th1 cytokine, and IL-4, a typical Th2 cytokine, were added to the culture to evaluate their effect on the IL-1β-induced secretion of TSLP. Inhibitors of p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK and stress-activated protein kinase/Jun amino-terminal kinase (SAPK/JNK) were added to the culture to examine intracellular signals involved in IL-1β-induced TSLP secretion. The expression of TSLP in endometrioma tissue was examined by immunohistochemistry. The concentration of TSLP in the serum and peritoneal fluid (PF) of women with or without endometriosis was measured with a specific ELISA.


RESULTS
IL-1β stimulated the expression of TSLP mRNA and secretion of TSLP protein from ESCs. IL-4 enhanced the IL-1β-induced TSLP secretion from ESCs, while IFNγ reduced it. Inhibitors of p42/44 MAPK, p38 MAPK and SAPK/JNK suppressed the IL-1β-induced secretion of TSLP from ESCs. Positive immunostaining of TSLP was observed in the stroma of endometrioma tissue. TSLP concentrations in the serum and PF were both higher in women with endometriosis compared with those without endometriosis.


CONCLUSIONS
The present study was only in vitro. The samples used for culture were endometrioma tissues, not including other types of endometriosis. Therefore, the present findings should be interpreted with caution.


CONCLUSIONS
This study provided new insights in the Th2 immune response-related mechanism in endometriosis.


BACKGROUND
This study is partly supported by grants from the Ministry of Health, Labour and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology. The authors have no conflicts of interest to declare.
Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan.
Yoko
Y
Urata
Yutaka
Y
Osuga
Gentaro
G
Izumi
Masashi
M
Takamura
Kaori
K
Koga
Miwako
M
Nagai
Miyuki
M
Harada
Tetsuya
T
Hirata
Yasushi
Y
Hirota
Osamu
O
Yoshino
Yuji
Y
Taketani
D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004715:Endometriosis / Q000209:etiology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D053583:Interleukin-1beta; D015847:Interleukin-4; D007371:Interferon-gamma; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases; D000094632:Thymic Stromal Lymphopoietin