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ABSTRACT: Interleukin-24 (IL-24) is a novel tumor suppressor gene, which has suppressor activity in a broad spectrum of human cancer cells. The present study aimed to elucidate the biological function of IL-24 and its receptors (IL-20R1, IL-20R2 and IL-22R1) in decidual stromal cells (DSCs) at human maternal-fetal interface. The DSCs behaviors in vitro were verified by viability (MTT) and apoptosis assay, respectively. Additionally, the effects of pregnancy associated hormones on IL-24 and the effect of IL-24 on the correspondent functional molecules were investigated by ELISA, in-cell western and flow cytometry, respectively. Here we found that DSCs expressed IL-24 and its receptors, and IL-24 obviously suppressed the viability and stimulated the apoptosis in DSCs. On the contrary, both anti-IL-24 and IL-22R1 neutralizing antibodies markedly promoted growth and reduced the apoptosis. Estrogen but not progesterone could significantly decrease IL-24 but not its receptors, and these effects could be abolished by the antagonist of estrogen receptor beta (ERβ). IL-24 significantly restricted the stimulatory effect of estrogen on the viability, anti-apoptosis, anti-apoptosis gene Bcl-2 and proliferation relative gene Ki-67 in DSCs. Our study has demonstrated that IL-24/IL-20R2/IL-22R1 axis is involved in the regulation of estrogen/ERβ signaling on the growth of DSCs through up-regulating the expression of Bcl-2 and Ki67, which suggests that estrogen plays an important role in DSCs growth of the early pregnancy through down-regulating IL-24.
Molecular Human Reproduction 05/2013; · 3.85 Impact Factor
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ABSTRACT: PROBLEM: To explore whether cervical carcinomas cells-derived thymic stromal lymphopoietin (TSLP) modulates the biologic behavior of vascular endothelial cells and herein participates in the angiogenesis in the cervical cancer pathogenesis. METHOD OF STUDY: We analyzed expression of TSLP and its receptor (TSLPR) in cervical cancer cells by immunohistochemistry, ELISA, and flow cytometry, respectively. We further investigated the effects of TSLP on the proliferation, apoptosis, activation, and angiogenesis in vitro of human umbilical vein endothelial cells (HUVECs). RESULTS: It has been found that the cervical cancer cells translate TSLP and endothelial cells express TSLPR in cervical cancer tissues. Both HeLa and CaSki cells secret TSLP in a time-dependent manner, and the ratio of TSLPR-positive HUVECs is about 30%. It has been showed that recombinant human TSLP (rhTSLP) can significantly increase Ki67 and CD62E expression in HUVECs and interleukin-6 (IL-6) levels from HeLa and CaSki cells; on the contrary, anti-human TSLP or TSLPR neutralizing antibody down-regulates the expression of Ki67, angiogenesis-relative molecules CD62E, and CD105 in HUVECs cocultured with HeLa or CasKi cells and inhibits IL-6 secretion from HeLa and CaSki cells. Moreover, both rhTSLP and endogenous TSLP from HeLa or CaSki cells obviously stimulate the proliferation, activation, and angiogenesis, but not influence the apoptosis of HUVECs in vitro. CONCLUSION: This study has demonstrated that TSLP secreted by cervical carcinomas cells is involved in the angiogenesis of cervical cancer in a paracrine manner.
American Journal Of Reproductive Immunology 03/2013; · 2.17 Impact Factor
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ABSTRACT: Chemokine CCL24 is the second member of eotaxins, a group of eosinophils' selectively chemoattractants. Via binding to its only receptor CCR3, CCL24 mainly mediates atopic disorders, parasitic infections and systemic diseases. It is well-known that CCR3 is expressed at the maternal-fetal interface; nevertheless whether CCL24 is located there and which role CCL24/CCR3 axis played is unclear. In this article, we assessed the expression of CCL24 and CCR3 in decidual stromal cells (DSCs) and trophoblasts, investigated the effects of DSCs-trophoblasts contact and pregnancy-associated hormones on the expression of CCR3 by DSCs, and last examined the role of trophoblasts-derived CCL24 on the proliferation, cell numbers and apoptosis of DSCs in vitro. We found that trophoblasts secrete chemokine CCL24, whereas DSCs express receptor CCR3. DSCs and trophoblasts co-culture had an raised level of CCL24 in culture supernatants, and the expression of CCR3 on DSCs was also obviously improved. Estrogen, progesterone and hCG up-regulated the expression of CCR3 on DSCs at appropriate concentration. CCL24 increased the proliferation and apoptosis of DSCs, whereas on the whole it promoted the number of DSCs. Thus, we conclude that by secreting CCL24 trophoblasts could promote the growth of DSCs; pregnancy associated environments such as DSCs-trophoblasts contact and hormones increased local CCL24/CCR3, which means a beneficial factor for the process of decidualization in human early pregnancy.
International journal of clinical and experimental pathology 01/2013; 6(6):1028-37. · 1.89 Impact Factor
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ABSTRACT: Chemokine CXCL8 (also known as IL-8) has been identified as a potential regulator of endometrial stromal cells (ESCs), but it is unclear how CXCL8 regulates the survival of ESCs in the pathogenesis of endometriosis.
We assessed the secretion of CXCL8 by enzyme-linked immunosorbent assays and the expression of its receptors, CXCR1 and CXCR2, by in-cell Western assay and immunohistochemistry. The effects of CXCL8 on the activation or expression of various cell mediators were also investigated by in-cell Western assay. The effects of CXCL8 on the proliferation, growth and apoptosis of ESCs in vitro were assessed by BrdU assays, cell counts and annexin V labeling, respectively.
Secretion of CXCL8 and expression of CXCR1 in the eutopic ESCs from women with endometriosis were significantly higher than that in control ESCs, but the expression of CXCR2 showed no significant difference between these two cell types. CXCL8 stimulated proliferation and growth and reduced apoptosis of ESCs in an autocrine manner, and these effects were abolished by anti-human CXCL8 and CXCR1 neutralizing antibodies and by a PI3K/Akt inhibitor. Moreover, CXCL8 up-regulated the expression of the anti-apoptotic proteins, survivin and Bcl-2, inhibited the expression of the Phosphatase and tensin homolog (PTEN) and activated the phosphorylation of Akt.
This study suggests that CXCL8 and CXCR1 are involved in the pathogenesis of endometriosis by up-regulating proliferation and growth and restricting apoptosis in ESCs by activating the PTEN/Akt pathway and mediating the expression of survivin and Bcl-2.
Human Reproduction 05/2012; 27(7):2107-16. · 4.47 Impact Factor
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ABSTRACT: To clarify the role and mechanism of CCL2 in regulating the biological functions of endometrial stromal cells (ESCs).
The CCL2 effect on the viability, proliferation, and invasion in the eutopic ESCs from endometriosis.
Research laboratories.
Patients with endometriosis aged 23-47 years.
None.
Signal transduction and downstream molecules from CCR2.
We have found that the secretion of CCL2 by the eutopic ESCs from endometriosis is higher than that of healthy ESCs without endometriosis. The CCL2 can enhance the viability, proliferation, and invasion of ESCs in a dosage and time-dependent manner. Anti-CCL2 neutralizing antibody and CCR2 antagonist can completely abolish the increase in viability, proliferation, and invasiveness of ESCs induced by CCL2. The CCL2 can increase the expression of proliferating cell nuclear antigen, survivin, and matrix metalloproteinase 2, and decrease the expression of tissue inhibitor of metalloproteinase 1 and 2, and promote the viability, proliferation and invasiveness of ESCs by activating Akt and MAPK/Erk1/2 signal pathway, but not p38 and JNK signal pathway.
CCL2 might play an important role in regulating the functions of ESCs through Akt and MAPK/Erk1/2 signal pathway, and overexpression of CCL2 in ESCs and peritoneal fluid (PF) would lead to onset and development of endometriosis.
Fertility and sterility 01/2012; 97(4):919-29. · 3.97 Impact Factor
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ABSTRACT: Our previous work has demonstrated that cyclosporin A (CsA) up-regulates but CD82 down-regulates the invasiveness of human trophoblasts. In the present study, we further investigated whether CsA can modulate the trophoblasts invasion through regulating the expression of CD82 in decidual stromal cells (DSCs). A co-culture model was established to investigate the effect of CsA on trophoblasts invasiveness. In-cell Western was performed to evaluate the expression of CD82, p53, β-catenin and the phosphorylation level of NF-κB p50 in DSCs. The secretion of CXCL12 of trophoblasts and DSCs was determined by enzyme-linked immunosorbent assay (ELISA). We found that CsA could not directly change the expression of CD82 in DSCs, but the CsA-treated trophoblasts significantly enhanced CD82 expression, NF-κB p50 phosphorylation and p53 expression, and decreased β-catenin expression in DSCs, and these effects could be abolished by anti-CXCL12 or CXCR4 neutralizing antibody. In addition, the invasiveness of trophoblast cells was markedly decreased after blocking CXCR4 of trophoblasts. Interestingly, when DSCs were pretreated with anti-CXCR4 neutralizing antibody, the invasiveness of trophoblast cells was enhanced in the coculture unit, and blocking CXCR4 on DSCs could reverse the decrease of trophoblasts invasiveness induced by CD82. Moreover, CsA further amplified these effects mediated by CXCL12 and CD82. Our results suggest that CsA not only promotes the trophoblasts invasiveness through stimulating the secretion of CXCL12, but also limits the invasiveness of trophoblasts by indirectly up-regulating the expression CD82. Therefore, CsA may contribute to the appropriate invasiveness of trophoblasts via strengthening the crosstalk between trophoblasts and DSCs.
International journal of clinical and experimental pathology 01/2012; 5(4):299-307. · 1.89 Impact Factor
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ABSTRACT: Tetraspanin CD82 is a wide-spectrum tumor metastasis suppressor that inhibits motility and invasiveness of cancer cells. Endometriosis is a benign gynecological disorder, but appears malignant behaviors including invasion, ectopic implantation and recurrence. This study is to elucidate the role of CD82 expression regulation in the pathogenesis of endometriosis. The short interfering RNA silence was established to analyze the roles of CD82, chemokine CCL2, and its receptor CCR2 in the invasiveness of endometrial stromal cells (ESCs). We have found that the mRNA and protein levels of CD82 in the primary normal ESCs from endometrium without endometriosis are significantly higher than that of the primary ESCs from eutopic endometrium and ectopic tissue. CD82 inhibits the invasiveness of ESCs by downregulating CCL2 secretion and CCR2 expression via mitogen-activated protein kinase (MAPK) and integrinβ1 signal pathway, and in turn upregulating the expression of TIMP1 and TIMP2 in an autocrine manner. The combination of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with 17β-estradiol can promote the invasion of ESCs via suppressing CD82 expression and stimulating CCL2 secretion and CCR2 expression, and the enhanced interaction of CCL2-CCR2 recruits more macrophages into the ectopic milieu in a paracrine manner, which further downregulates CD82 expression in the ectopic ESCs. Our study has demonstrated for the first time that the abnormal lower CD82 expression in ESCs induced by TCDD and estrogen may be an important molecular basis of endometriosis pathogenesis through enhancing the CCL2 secretion and CCR2 expression and the invasion of ESCs via MAPK and integrinβ1 signal pathway.
Journal of Molecular Endocrinology 06/2011; 47(2):195-208. · 3.48 Impact Factor
