SB203580, a p38 mitogen-activated protein kinase inhibitor, suppresses the development of endometriosis by down-regulating proinflammatory cytokines and proteolytic factors in a mouse model

Zhou, Weidong; Yang, Huiming; Wang, Qin; Su, Dongyin; Liu, Fu-An; Zhao, Min; Chen, Qionghua; Chen, Qing‐Xi

doi:10.1093/humrep/deq287

Cited by 42 publications

(35 citation statements)

References 31 publications

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“…Accordingly, these MAPK inhibitors may hinder the progression of the disease by suppressing both inflammation and Th2 immune response. Actually, the efficacy of inhibitors of p42/44 MAPK and p38 MAPK to subside the disease has been demonstrated in mouse models of endometriosis (Yoshino et al, 2006;Ngô et al, 2010;Zhou et al, 2010). In contrast, protein kinase A inhibitor H89 and Janus kinase 3 inhibitor CP-690550, which are not expected to affect the pathways activated by IL-1b, did not affect the secretion of IL-1b-induced increase in TSLP secretion (Supplementary data, Fig.…”

Section: Discussionmentioning

confidence: 95%

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

et al. 2012

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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.

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Section: Discussionmentioning

confidence: 95%

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

et al. 2012

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“…Statistically significant reductions in p38 MAPK phosphorylation and in the weight and size of lesions were observed. In the peritoneal fluid and cells of treated animals, IL-1b, TNF-a, MMP-2 and MMP-9 mRNA levels and IL-6 and MCP-1 protein levels were statistically significantly decreased, evidencing an improvement in the inflammatory environment generated in the endometriotic-like peritoneal cavity of rodents (39,40).…”

Section: Mitogen-activated Protein Kinase Inhibitorsmentioning

confidence: 89%

“…Because activation of p38 MAPK may be involved in the pathogenesis of endometriosis, specific inhibitors of this molecule have been tested as a therapeutic option (39,40).…”

Section: Mitogen-activated Protein Kinase Inhibitorsmentioning

confidence: 99%

Pharmacologic therapies in endometriosis: a systematic review

Soares¹,

Martínez-Varea

Hidalgo-Mora

et al. 2012

Fertility and Sterility

137

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“…The following conditions were applied to reverse transcription: 37°C for 15 min and one cycle; 85°C for 5 s. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out using an SYBR PrimeScript RT-PCR kit, as previously described. 25 The mRNA expression of vinculin and IL-4 were normalized to RNA loading for each sample, with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA serving as an internal standard. The primers used for qRT-PCR are listed in Table 1.…”

Section: Rna Extraction and Quantitative Reverse Transcription-polymementioning

confidence: 99%

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

Yang

Zhou

et al. 2016

J of Obstet and Gynaecol

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Aim: Lipoxin A 4 (LXA 4 ) can function as an endogenous 'breaking signal' in inflammation and plays an important role in the progression of endometriosis. The proteome responses to interleukin-1β (IL-1β) or LXA 4 in human endometriotic stromal cells (ESC) are not well understood. Methods: In this study, primary ESC were cultured from ovarian endometriosis tissue. Three groups were established: the control group; the IL-1β stimulation group; and the IL-1β and LXA 4 incubation group. Proteins were assessed on 2-D polyacrylamide gel electrophoresis (2D-PAGE), and differentially expressed protein spots were further identified on matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MALDI-TOF-MS). Wound healing and transwell assays were performed to assess the migration and invasion of ESC after treatment. Results: In total, 40 differentially expressed protein spots were identified successfully on MALDI-TOF-MS. The proteins identified were related to cell structure, metabolism, signal transduction, protein synthesis and membrane structure, processes that may be involved in the development of endometriosis. Vinculin and IL-4 were further analyzed on western blot and quantitative real-time polymerase chain reaction. Moreover, LXA 4 could suppress the migration and invasion of ESC induced by IL-1β. Conclusion: LXA 4 may inhibit the progression of endometriosis partly by lowering or raising the effect of IL-1β, mediated via some inflammation-related proteins (e.g. vinculin) and immune response-related protein (e.g. IL-4) in vitro.

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SB203580, a p38 mitogen-activated protein kinase inhibitor, suppresses the development of endometriosis by down-regulating proinflammatory cytokines and proteolytic factors in a mouse model

Abstract: SB203580 may suppress the development of EM by inhibiting expression of proinflammatory cytokines and proteolytic factors. p38 MAPK might play a key role in progression of EM.

Cited by 42 publications

References 31 publications

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

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

Pharmacologic therapies in endometriosis: a systematic review

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

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SB203580, a p38 mitogen-activated protein kinase inhibitor, suppresses the development of endometriosis by down-regulating proinflammatory cytokines and proteolytic factors in a mouse model

Abstract: SB203580 may suppress the development of EM by inhibiting expression of proinflammatory cytokines and proteolytic factors. p38 MAPK might play a key role in progression of EM.

Cited by 42 publications

References 31 publications

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

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

Pharmacologic therapies in endometriosis: a systematic review

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

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