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

Abstract

STUDY QUESTION:

Is thymic stromal lymphopoietin (TSLP) involved in the pathophysiology of endometriosis?

SUMMARY ANSWER:

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.

STUDY FUNDING:

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.

• Authors: Yoko Urata, Yutaka Osuga, Gentaro Izumi, Masashi Takamura, Kaori Koga, Miwako Nagai, Miyuki Harada, Tetsuya Hirata, Yasushi Hirota, Osamu Yoshino, Yuji Taketani
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 27 Issue 10 Pg. 3028-35 (Oct 2012) ISSN: 1460-2350 [Electronic] England
• PMID: 22888172 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interleukin-1beta
• Interleukin-4
• Interferon-gamma
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinase 1
• p38 Mitogen-Activated Protein Kinases
• Thymic Stromal Lymphopoietin

Topics

• Cells, Cultured
• Cytokines (genetics, metabolism, physiology)
• Endometriosis (etiology, pathology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Gene Expression (drug effects)
• Humans
• Immunohistochemistry
• Interferon-gamma (pharmacology)
• Interleukin-1beta (pharmacology)
• Interleukin-4 (pharmacology)
• JNK Mitogen-Activated Protein Kinases (pharmacology)
• Mitogen-Activated Protein Kinase 1 (pharmacology)
• Polymerase Chain Reaction
• Stromal Cells (drug effects, metabolism)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors)
• Thymic Stromal Lymphopoietin