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)-1b 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-1b, 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 g (IFNg), a typical Th1 cytokine, and IL-4, a typical Th2 cytokine, were added to the culture to evaluate their effect on the IL-1b-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-1b-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-1b stimulated the expression of TSLP mRNA and secretion of TSLP protein from ESCs. IL-4 enhanced the IL-1b-induced TSLP secretion from ESCs, while IFNg reduced it. Inhibitors of p42/44 MAPK, p38 MAPK and SAPK/JNK suppressed the IL-1b-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.

Simultaneous Detection and Evaluation of Four Subsets of CD4+ T Lymphocyte in Lesions and Peripheral Blood in Endometriosis

“…34 Previously, our group demonstrated for the first time the presence of Th17 in endometriosis lesion. The proportion of Th1 was significantly lower in endometriosis lesions than in endometrium, whereas the proportion of Th17 was significantly higher in endometriosis lesions than in endometrium.…”

“…The age of patients in Group C (33.5, 27-43) was not significantly different from that of patients in Group D (31,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). Six women were in the proliferative phase and four were in the secretory phase (Group C), and four women were in proliferative phase and six were in secretory phase (Group D) at the time of sample collection.…”

Involvement of immune cells in the pathogenesis of endometriosis

“…In the endometriosis lesion, the frequency of Th1 cells is lower than in normal endometrium . Furthermore, Th2 cytokines, such as IL‐4, IL‐10, and TSLP, have been shown to contribute to disease progression. Studies of peripheral blood, however, have revealed a higher Th1/Th2 cytokine ratio and Th1 cell frequency in endometriosis patients compared with controls.…”

Effect of interleukin‐1β and lipoxin A4 in human endometriotic stromal cells: Proteomic analysis

“…In addition, IL-1β may also contribute to the Th2 immune response by improving the secretion of thymic stromal lymphopoietin. 38 Therefore, in an inflammatory ESC were stimulated with IL-1β (1 ng/mL) or vehicle (medium) for 24 h, or were pre-incubated with lipoxin (LX)A 4 alone for 24 h, or pre-incubated with LXA 4 (100 nmol/L, 30 min) and stimulated with IL-1β (1 ng/mL, 24 h). These experiments were performed three times using different batches of cells, and data are given as mean ± SEM.…”