AIM： To explore the effect of recombinant human interleukin-11 （rhIL-11） on the expressions of interleukin-11 receptor α-chain （IL-11Rα） and an additional signal transducer glycoprotein 130 （gp130） in intesti...AIM： To explore the effect of recombinant human interleukin-11 （rhIL-11） on the expressions of interleukin-11 receptor α-chain （IL-11Rα） and an additional signal transducer glycoprotein 130 （gp130） in intestinal epithelium cell line-6 （IEC-6） after neutron irradiation. METHODS： Cultured IEC-6 cells were exposed to 4.0Gy neutron and treated with 100 ng/mL rhIL-11 12 h prior to or immediately after irradiation. The apoptosis and necrosis rates and expressions of IL-11Rα and gp130 were observed by flow cytometry, immunohistochemistry, Western blot and image analysis. RESULTS： The apoptosis rate of IEC-6 cells was increased by irradiation at 6 h （P 〈 0.01）, IL-11 stimulation resulted in a decreased apoptosis rate in irradiated IEC-6 cells （P 〈 0.05）. In normal control IEC-6 cells, intense immunoreactivity of IL-11Rα was located within the cell membrane and cytoplasm. The level of IL-11Rα expression significantly decreased at 6 h after irradiation （P 〈 0.01） and restored at 24 h after irradiation. In IEC-6 cells treated with both radiation and rhIL-11, the level of IL- 11Rα expression was higher than that of irradiated cells （P 〈 0.05）. When it came to gp130 protein, it was located in the cytoplasm of IEC-6 cells. After irradiation, we found a progressive decrease in the expression of gp130 protein （P 〈 0.05） in 48 hours post-radiation, while in rhIL-11-stimulated cells, it came back to normal level at 24 h after irradiation and decreased at 48 h, but was still higher than that of only irradiated cells （P 〈 0.05）. CONCLUSION： rhIL-11 can protect IEC-6 cells from neutron irradiation. The protective effect of rhIL-11 might be connected with its ability to up-regulate the expressions of specific ligand-binding subunit IL-11Rα and signal-transducing subunit gp130.展开更多
Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is uncle...Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is unclear, and the effective treatments are lacking to date. In this study, we aim to explore the molecular mechanism by which interleukin-11(IL-11) affects silica particles-induced lung inflammation and fibrosis. We observed that IL-11 expressions in mouse lungs were significantly increased after silica exposure, and maintained at high levels across both inflammation and fibrosis phase. Immunofluorescent dual staining further revealed that the overexpression of IL-11 mainly located in mouse lung epithelial cells and fibroblasts. Using neutralizing anti-IL-11 antibody could effectively alleviate the overexpression of pro-inflammatory cytokines(i.e., interleukin-6 and tumor necrosis factor-α) and fibrotic proteins(i.e., collagen type I and matrix metalloproteinase-2) induced by silica particles. Most importantly, the expressions of IL-11 receptor subunit α(IL-11Rα), Glycoprotein130(GP130), and phosphorylated extracellular signal-regulated kinase(p-ERK) were significantly increased in response to silica, whereas blocking of IL-11 markedly reduced their levels. All findings suggested that the overexpression of IL-11 was involved in the pathological of silicosis, while neutralizing IL-11 antibody could effectively alleviate the silica-induced lung inflammation and fibrosis by inhibiting the IL-11Rα/GP130/ERK signaling pathway. IL-11 might be a promising therapeutic target for lung inflammation and fibrosis caused by silica particles exposure.展开更多
BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC ...BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families.AIM To investigate the expression and significance of mucin 1(MUC1)and interleukin-11(IL-11)in the intestinal mucosa of infants with neonatal NEC after surgery.METHODS Forty-eight postoperative intestinal mucosal specimens from children with NEC(NEC group)and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia(control group)were collected in our hospital.Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups.The serum levels of tumor necrosis factor-α(TNF-α)and IL-1βin the two groups were measured by enzyme-linked immunosorbent assay,and the relationship between MUC-1 and IL-11 protein expression and serum TNF-αand IL-1βlevels was analyzed by the linear correlation method.RESULTS The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group,and the difference was statistically significant(P<0.05).The levels of serum TNF-αand IL-1βin the NEC group were significantly higher than those in the control group(P<0.05).The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-αand IL-1βlevels(P<0.05).There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-αand IL-1βin the NEC group.CONCLUSION The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery.This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.展开更多
Objective： To evaluate the efficacy and safety of recombinant human interleukin-11 （rhIL-11） for the chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer. Methods： It was an opened and no...Objective： To evaluate the efficacy and safety of recombinant human interleukin-11 （rhIL-11） for the chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer. Methods： It was an opened and non-randomized controlled clinical study. When the platelet counts was under 75 × 10^9/L after chemotherapy, rhlL-11 was administered 25 μg/（kg·d） as a daily SC injection last for 7-14 days, or discontinued when platelet counts 〉 100 × 10^9/L. Results： Seventysix patients were enrolled into this study. The treatment group and the control group had thirty-eight cases, respectively. The mean recovery time to PLT ≥ 100 × 10^9/L was 8.1 days in treatment group, while in control group was 12.2 days （P 〈 0.01）. Moreover, the mean recovery time from PLT 〈_ 50 × 10^9/L to 〉 100 × 10^9/L was 8.9 days in treatment group, while in control group was 12.9 days （P 〈 0.05）. There was a statistical difference between the two groups. Major side effects included edema, fever, articular muscle soreness, but they were all mild and well tolerable. Conclusion： rhIL-11 can be safely and effectively used for the treatment of chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer.展开更多
AIM： There is strong evidence that interleukin-11 （IL-11） is involved in the regulation of tumor progression, cellular growth and differentiation. Recently, interleukin-11 receptor （IL-11R） has been detected on s...AIM： There is strong evidence that interleukin-11 （IL-11） is involved in the regulation of tumor progression, cellular growth and differentiation. Recently, interleukin-11 receptor （IL-11R） has been detected on some cancer cells. In this study, we investigated the expression of IL-11 and IL-11R in colorectal adenocarcinoma. METHODS： To elucidate the involvement of IL-11 and IL-11Rα in human intestinal adenocarcinomas, we examined 115 cases of surgically resected human colonic adenocarcinoma and 11 cases of adenoma by immunohistochemistry and Western blotting. RESULTS： Among 115 cases of adenocarcinoma, 100 cases （87.0%） showed positive staining in the cytoplasm of carcinoma cells for the IL-11, and 87 cases （75.6%） were positive for the IL-11Ra. Six cases （54.5%） and four cases （36.4%） of 11 adenomas were positive for IL-11 and IL-11Ra, respectively. The expression of IL- 11Ra correlated with the histological differentiation （P=0.033503）, the depth of tumor invasion （P= 0.006395）, Dukes＇ classification （P= 0.015648） and lymphatic invasion （P= 0.003865）. However, the expression of IL- 11Rα was not correlated with the venous invasion and the presence of lymph node metastasis. The expression of IL-11 was not correlated with any clinicopathological factors. In Western blot analysis, two human colorectal carcinoma cell lines and four tissues of surgically resected human carcinoma expressed both IL-11 and IL-11Rα proteins. CONCLUSION： IL-11 and IL-11Rα are highly expressed in human colorectal adenocarcinoma and the IL-11Rα expression is correlated with clinicopathological factors, These findings suggest that the expression of IL-11Rα is an important factor for the invasion of human colorectal adenocarcinoma.展开更多
Interleukin-11 （IL-11） is a cytokine of IL-6 family that mediates signal transduction through a common signal transduction molecule glycoprotein 130gp130. JAK/STAT, Ras/Erk and PI3K-mediated pathways are involved in...Interleukin-11 （IL-11） is a cytokine of IL-6 family that mediates signal transduction through a common signal transduction molecule glycoprotein 130gp130. JAK/STAT, Ras/Erk and PI3K-mediated pathways are involved in the IL-11 signaling pathway. IL-11 has traditionally been thought to be an anti-inflammatory cytokine that has a complex role in the body＇s immune response. Simultaneously, the activation of STAT3 by IL-11 provides a functional link to support the survival and growth of cancer cells. There is also evidence that IL-11 may play a role in promoting liver cancer through wound healing mechanisms. In recent years, studies have found that IL-11 could stimulate the development of tumors via promoting the proliferation and inhibiting the apoptosis of cancer cells, mediating the tolerance of cancer cells to radiotherapy and chemotherapy, and mediating the growth and survival of early microtransferred colonies. Sustained activation of JAK-STAT and PI3K-AKT signaling pathway, up-regulating the expression of IL-11 receptor and hypoxia microenvironment mediated by HIF-1a and AP-1 transcription factors are involved in the progression of cancer. Therefore, targeted therapies that treat the over expression of IL-11 or IL-11 receptors and IL-11 signaling pathway such as the JAK 1/2 and STAT3 inhibitor in cancer patients has the potential to completely relieve the tumor, which may provide us a new idea for the treatment of cancer.展开更多
食源性蛋白淀粉样纤维化聚集具有独特的结构特性,蚕豆11S蛋白(fava bean 11S protein,FP)作为一种可持续蛋白资源,表现出巨大的潜力。该研究探究了蚕豆11S蛋白淀粉样纤维化聚集(fibrotic aggregation of 11S protein in fava bean,FPF)...食源性蛋白淀粉样纤维化聚集具有独特的结构特性,蚕豆11S蛋白(fava bean 11S protein,FP)作为一种可持续蛋白资源,表现出巨大的潜力。该研究探究了蚕豆11S蛋白淀粉样纤维化聚集(fibrotic aggregation of 11S protein in fava bean,FPF)在形成过程中的动态演变,包括其结构表征和功能特性。6 g/100 mL的FP通过酸热处理(pH 2,85℃)不同时间(0~24 h)后得到FPF。处理后的样品通过硫黄素T、荧光、二酪氨酸、透射电子显微镜、傅里叶红外光谱等进行结构表征,结果表明FP先在酸热过程中水解成多肽,再自组装成富含β-折叠结构的FPF(由0 h的34.44%增加到24 h的45.89%)。通过起泡性、乳化性和凝胶特性等对FPF功能特性进行表征,与FP相比,反应24 h后的FPF具有更好的起泡性、乳化性和凝胶特性。此外,FPF在体外细胞实验中没有表现出细胞毒性。研究结果为FPF的形成规律提供了理论支撑。展开更多
基金Supported by National Natural Science Foundation of China,No. 30370438
文摘AIM： To explore the effect of recombinant human interleukin-11 （rhIL-11） on the expressions of interleukin-11 receptor α-chain （IL-11Rα） and an additional signal transducer glycoprotein 130 （gp130） in intestinal epithelium cell line-6 （IEC-6） after neutron irradiation. METHODS： Cultured IEC-6 cells were exposed to 4.0Gy neutron and treated with 100 ng/mL rhIL-11 12 h prior to or immediately after irradiation. The apoptosis and necrosis rates and expressions of IL-11Rα and gp130 were observed by flow cytometry, immunohistochemistry, Western blot and image analysis. RESULTS： The apoptosis rate of IEC-6 cells was increased by irradiation at 6 h （P 〈 0.01）, IL-11 stimulation resulted in a decreased apoptosis rate in irradiated IEC-6 cells （P 〈 0.05）. In normal control IEC-6 cells, intense immunoreactivity of IL-11Rα was located within the cell membrane and cytoplasm. The level of IL-11Rα expression significantly decreased at 6 h after irradiation （P 〈 0.01） and restored at 24 h after irradiation. In IEC-6 cells treated with both radiation and rhIL-11, the level of IL- 11Rα expression was higher than that of irradiated cells （P 〈 0.05）. When it came to gp130 protein, it was located in the cytoplasm of IEC-6 cells. After irradiation, we found a progressive decrease in the expression of gp130 protein （P 〈 0.05） in 48 hours post-radiation, while in rhIL-11-stimulated cells, it came back to normal level at 24 h after irradiation and decreased at 48 h, but was still higher than that of only irradiated cells （P 〈 0.05）. CONCLUSION： rhIL-11 can protect IEC-6 cells from neutron irradiation. The protective effect of rhIL-11 might be connected with its ability to up-regulate the expressions of specific ligand-binding subunit IL-11Rα and signal-transducing subunit gp130.
基金supported by the National Natural Science Foundation of China (Nos. 81803205 and 81872593)the China Postdoctoral Science Foundation (No. 2019T120665)+2 种基金the Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology (No. OHIC_(2)020G01)the Fundamental Research Funds for the Central Universities (No. 2020kfy XJJS005)the Open Projects Program of Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment (No. 2017B030314152)。
文摘Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is unclear, and the effective treatments are lacking to date. In this study, we aim to explore the molecular mechanism by which interleukin-11(IL-11) affects silica particles-induced lung inflammation and fibrosis. We observed that IL-11 expressions in mouse lungs were significantly increased after silica exposure, and maintained at high levels across both inflammation and fibrosis phase. Immunofluorescent dual staining further revealed that the overexpression of IL-11 mainly located in mouse lung epithelial cells and fibroblasts. Using neutralizing anti-IL-11 antibody could effectively alleviate the overexpression of pro-inflammatory cytokines(i.e., interleukin-6 and tumor necrosis factor-α) and fibrotic proteins(i.e., collagen type I and matrix metalloproteinase-2) induced by silica particles. Most importantly, the expressions of IL-11 receptor subunit α(IL-11Rα), Glycoprotein130(GP130), and phosphorylated extracellular signal-regulated kinase(p-ERK) were significantly increased in response to silica, whereas blocking of IL-11 markedly reduced their levels. All findings suggested that the overexpression of IL-11 was involved in the pathological of silicosis, while neutralizing IL-11 antibody could effectively alleviate the silica-induced lung inflammation and fibrosis by inhibiting the IL-11Rα/GP130/ERK signaling pathway. IL-11 might be a promising therapeutic target for lung inflammation and fibrosis caused by silica particles exposure.
基金Suzhou Science and Technology Program,No.SLT202005Suzhou Municipal Commission of Health and Family Planning,No.LCZX202031+1 种基金Suzhou New District Science and Technology Plan,No.2019Z009Independent Innovation Project of National High Tech Development Zone Hospital,No.SGY2018C03.
文摘BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families.AIM To investigate the expression and significance of mucin 1(MUC1)and interleukin-11(IL-11)in the intestinal mucosa of infants with neonatal NEC after surgery.METHODS Forty-eight postoperative intestinal mucosal specimens from children with NEC(NEC group)and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia(control group)were collected in our hospital.Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups.The serum levels of tumor necrosis factor-α(TNF-α)and IL-1βin the two groups were measured by enzyme-linked immunosorbent assay,and the relationship between MUC-1 and IL-11 protein expression and serum TNF-αand IL-1βlevels was analyzed by the linear correlation method.RESULTS The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group,and the difference was statistically significant(P<0.05).The levels of serum TNF-αand IL-1βin the NEC group were significantly higher than those in the control group(P<0.05).The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-αand IL-1βlevels(P<0.05).There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-αand IL-1βin the NEC group.CONCLUSION The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery.This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.
文摘Objective： To evaluate the efficacy and safety of recombinant human interleukin-11 （rhIL-11） for the chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer. Methods： It was an opened and non-randomized controlled clinical study. When the platelet counts was under 75 × 10^9/L after chemotherapy, rhlL-11 was administered 25 μg/（kg·d） as a daily SC injection last for 7-14 days, or discontinued when platelet counts 〉 100 × 10^9/L. Results： Seventysix patients were enrolled into this study. The treatment group and the control group had thirty-eight cases, respectively. The mean recovery time to PLT ≥ 100 × 10^9/L was 8.1 days in treatment group, while in control group was 12.2 days （P 〈 0.01）. Moreover, the mean recovery time from PLT 〈_ 50 × 10^9/L to 〉 100 × 10^9/L was 8.9 days in treatment group, while in control group was 12.9 days （P 〈 0.05）. There was a statistical difference between the two groups. Major side effects included edema, fever, articular muscle soreness, but they were all mild and well tolerable. Conclusion： rhIL-11 can be safely and effectively used for the treatment of chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer.
文摘AIM： There is strong evidence that interleukin-11 （IL-11） is involved in the regulation of tumor progression, cellular growth and differentiation. Recently, interleukin-11 receptor （IL-11R） has been detected on some cancer cells. In this study, we investigated the expression of IL-11 and IL-11R in colorectal adenocarcinoma. METHODS： To elucidate the involvement of IL-11 and IL-11Rα in human intestinal adenocarcinomas, we examined 115 cases of surgically resected human colonic adenocarcinoma and 11 cases of adenoma by immunohistochemistry and Western blotting. RESULTS： Among 115 cases of adenocarcinoma, 100 cases （87.0%） showed positive staining in the cytoplasm of carcinoma cells for the IL-11, and 87 cases （75.6%） were positive for the IL-11Ra. Six cases （54.5%） and four cases （36.4%） of 11 adenomas were positive for IL-11 and IL-11Ra, respectively. The expression of IL- 11Ra correlated with the histological differentiation （P=0.033503）, the depth of tumor invasion （P= 0.006395）, Dukes＇ classification （P= 0.015648） and lymphatic invasion （P= 0.003865）. However, the expression of IL- 11Rα was not correlated with the venous invasion and the presence of lymph node metastasis. The expression of IL-11 was not correlated with any clinicopathological factors. In Western blot analysis, two human colorectal carcinoma cell lines and four tissues of surgically resected human carcinoma expressed both IL-11 and IL-11Rα proteins. CONCLUSION： IL-11 and IL-11Rα are highly expressed in human colorectal adenocarcinoma and the IL-11Rα expression is correlated with clinicopathological factors, These findings suggest that the expression of IL-11Rα is an important factor for the invasion of human colorectal adenocarcinoma.
文摘Interleukin-11 （IL-11） is a cytokine of IL-6 family that mediates signal transduction through a common signal transduction molecule glycoprotein 130gp130. JAK/STAT, Ras/Erk and PI3K-mediated pathways are involved in the IL-11 signaling pathway. IL-11 has traditionally been thought to be an anti-inflammatory cytokine that has a complex role in the body＇s immune response. Simultaneously, the activation of STAT3 by IL-11 provides a functional link to support the survival and growth of cancer cells. There is also evidence that IL-11 may play a role in promoting liver cancer through wound healing mechanisms. In recent years, studies have found that IL-11 could stimulate the development of tumors via promoting the proliferation and inhibiting the apoptosis of cancer cells, mediating the tolerance of cancer cells to radiotherapy and chemotherapy, and mediating the growth and survival of early microtransferred colonies. Sustained activation of JAK-STAT and PI3K-AKT signaling pathway, up-regulating the expression of IL-11 receptor and hypoxia microenvironment mediated by HIF-1a and AP-1 transcription factors are involved in the progression of cancer. Therefore, targeted therapies that treat the over expression of IL-11 or IL-11 receptors and IL-11 signaling pathway such as the JAK 1/2 and STAT3 inhibitor in cancer patients has the potential to completely relieve the tumor, which may provide us a new idea for the treatment of cancer.
