Interleukin-1β stimulates the secretion of thymic stromal lymphopoietin (TSLP) from endometrioma stromal cells: possible involvement of TSLP in endometriosis
Authors: Urata, Yoko; Osuga, Yutaka; Izumi, Gentaro; Takamura, Masashi; Koga, Kaori; Nagai, Miwako; Harada, Miyuki; Hirata, Tetsuya; Hirota, Yasushi; Yoshino, Osamu; Taketani, Yuji
Source: Human Reproduction, Volume 27, Number 10, 18 October 2012 , pp. 3028-3035(8)
Publisher: Oxford University Press
Is thymic stromal lymphopoietin (TSLP) involved in the pathophysiology of endometriosis?
TSLP is up-regulated by interleukin (IL)-1β and may be involved in the development of endometriosis.
WHAT IS KNOWN ALREADY
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.
STUDY DESIGN, SIZE, DURATION
A laboratory study.
PARTICIPANTS/MATERIALS, SETTING, 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.
MAIN RESULTS AND THE ROLE OF CHANCE
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.
LIMITATIONS, REASONS FOR CAUTION
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.
WIDER IMPLICATIONS OF THE FINDINGS
This study provided new insights in the Th2 immune response-related mechanism in endometriosis.
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.
Document Type: Research Article
Publication date: 18 October 2012
- Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.
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- In this Subject: Anatomy & Physiology , Obstetrics & Gynecology
- By this author: Urata, Yoko ; Osuga, Yutaka ; Izumi, Gentaro ; Takamura, Masashi ; Koga, Kaori ; Nagai, Miwako ; Harada, Miyuki ; Hirata, Tetsuya ; Hirota, Yasushi ; Yoshino, Osamu ; Taketani, Yuji