Objective To obtain precise data on the changes in the levels of 29 cytokines in mice after high or low linear energy transfer(LET)irradiation and to develop an accurate model of radiation exposure based on the cytoki...Objective To obtain precise data on the changes in the levels of 29 cytokines in mice after high or low linear energy transfer(LET)irradiation and to develop an accurate model of radiation exposure based on the cytokine levels after irradiation.Methods Plasma samples harvested from mice at different time points after carbon-ion or X-ray irradiation were analyzed using meso-scale discovery(MSD),a high-throughput and sensitive electrochemiluminescence measurement technique.Dose estimation equations were set up using multiple linear regression analysis.Results The relative levels of IL-6 at 1 h,IL-5 and IL-6 at 24 h,and IL-5,IL-6 and IL-15 at 7 d after irradiation with two intensities increased dose-dependently.The minimum measured levels of IL-5,IL-6 and IL-15 were up to 4.0076 pg/mL,16.4538 pg/mL and 0.4150 pg/mL,respectively.In addition,dose estimation models were established and verified.Conclusions The MSD assay can provide more accurate data regarding the changes in the levels of the cytokines IL-5,IL-6 and IL-15.These cytokines could meet the essential criteria for radiosensitive biomarkers and can be used as radiation indicators.Our prediction models can conveniently and accurately estimate the exposure dose in irradiated organism.展开更多
AIM: To investigate if an immune imbalance may account for the development and progression of chronic radiation enteritis. We analyzed the Th1/Th2 immune response profile early and 6 mo after fractionated colorectal ...AIM: To investigate if an immune imbalance may account for the development and progression of chronic radiation enteritis. We analyzed the Th1/Th2 immune response profile early and 6 mo after fractionated colorectal irradiation. METHODS: A rat model of fractionated colorectal γ-irradiation (4-Gy fractions, 3 fractions per week) was designed to investigate the effects of cumulative dose on inflammatory mediators (cytokines and chemo- kines) and immune response (Th1/Th2 profile and immunosuppressive mediator IL-10) during acute (early) response and 6 mo after the end of fractionated irradiation (chronic response). Analyses were performed 1 d after the cumulative doses of 16 Gy and 36 Gy and 1 d, 3 d, and 26 wk after the cumulative dose of 52 Gy. RESULTS: Without causing histological damage, fractionated radiation induced elevated expression of IL-1β, TNFα, MCP-1, and iNOS in distal colonic mucosa during the early post-irradiation phase. At that time, a Th2 profile was confirmed by expression of both the Th2- specific transcription factor GATA-3 and the chemokine receptor CCR4 and by suppression of the Thl cytokine IFNγ/IP-10 throughout the irradiation protocol. After 6 mo, despite the 2-fold reduction of iNOS and MCP-1 levels, the Th2 profile persisted, as shown by a 50% reduction in the expression of the Thl transcription factor T-bet, the chemokine receptor CCXCR3, and the IFNγ/ STAT1 pathway. At the same time-point, the immunosuppressive IL-10/STAT3 pathway, known to regulate the Th1/Th2 balance, was expressed, in irradiated rats, at approximately half its level as compared to controls.This suppression was associated with an overexpression of SOCS3, which inhibits the feedback of the Thl polarization and regulates IL-10 production. CONCLUSION: Colorectal irradiation induces Th2 polarization, defective IL-10/STAT3 pathway activation and SOCS3 overexpression. These changes, in turn, maintain a immunological imbalance that persists in the long term.展开更多
AIM: To investigate their expression and activity in the rat ileum after exposure to ionizing radiation along with that of the cellular effectors and molecular mediators involved in the regulation of MMPs. METHODS: ...AIM: To investigate their expression and activity in the rat ileum after exposure to ionizing radiation along with that of the cellular effectors and molecular mediators involved in the regulation of MMPs. METHODS: Rats were exposed to a single 10-Gy dose of X-rays delivered to the abdomen. A combination of methods, such as zymography, immunohistochemistry and real time reverse transcriptase-polymerase chain reaction, were used to localize and quantify MMPs and the molecules involved in MMP activating and inhibitory pathways (plasmin/ plasminogen, TIMPs), CD^8+, as well as inflammatory (interleukin (IL)-1β, IL-8, tumor necrosis factor-s, TNF-α) and fibrogenic mediators (transforming growth factor- β1-3) within ileal tissue at 1, 3, and 7 d after irradiation. RESULTS: A marked increase in MMP-2 and -14 mRNA and protein levels associated with an increased activity of MMP-2 was observed in irradiated ileal tissue. MMP-2 and -14 expression was mainly observed in inflammatory, epithelial, and mesenchymal cells, whereas a slight increase in MMP-3 expression was detected in the few infiltrating macrophages at d i after irradiation. Conversely, MMP-1, -7, and -9 mRNA levels were not found to be affected by abdominal irradiation. Irradiation was found to induce disappearance of CD^8+ cells. Furthermore, we have observed that TNF-α and IL-1β protein levels increased 6 h after irradiation, whereas those of IL-8 only increased after 3 d and was concomitant with neutrophil infiltration. In addition, the expressions of molecules involved in MMP activating and inhibitory pathways (urokinase-type plasminogen activator andtissue-type plasminogen activator; TIMP-1, TIMP-2, and plasminogen activator-inhibitor-i) were found to be increased after abdominal irradiation. CONCLUSION: This study showed that abdominal irradiation induces an acute remodeling of the ileum associated with an increased expression of MMPs and TIMPs that do not involve CD^8+ T cells but involve mesenchymal and epithelial cells, although to a lesser extent, and probably even soluble inflammatory and fibrogenic mediators.展开更多
To investigate a possible therapeutic mechanism of cell therapy in the field of cerebral palsy using granulocyte-colony stimulating factor(G-CSF)-mobilized peripheral blood mononuclear cells(m PBMCs),we compared t...To investigate a possible therapeutic mechanism of cell therapy in the field of cerebral palsy using granulocyte-colony stimulating factor(G-CSF)-mobilized peripheral blood mononuclear cells(m PBMCs),we compared the expression of inflammatory cytokines and neurotrophic factors in PBMCs and m PBMCs from children with cerebral palsy to those from healthy adult donors and to cord blood mononuclear cells donated from healthy newborns.No significant differences in expression of neurotrophic factors were found between PBMCs and m PBMCs.However,in cerebral palsy children,the expression of interleukin-6 was significantly increased in m PBMCs as compared to PBMCs,and the expression of interleukin-3 was significantly decreased in m PBMCs as compared to PBMCs.In healthy adults,the expression levels of both interleukin-1βand interleukin-6 were significantly increased in m PBMCs as compared to PBMCs.The expression of brain-derived neurotrophic factors in m PBMC from cerebral palsy children was significantly higher than that in the cord blood or m PBMCs from healthy adults.The expression of G-CSF in m PBMCs from cerebral palsy children was comparable to that in the cord blood but significantly higher than that in m PBMCs from healthy adults.Lower expression of pro-inflammatory cytokines(interleukin-1β,interleukin-3,and-6)and higher expression of anti-inflammatory cytokines(interleukin-8 and interleukin-9)were observed from the cord blood and m PBMCs from cerebral palsy children rather than from healthy adults.These findings indicate that m PBMCs from cerebral palsy and cord blood mononuclear cells from healthy newborns have the potential to become seed cells for treatment of cerebral palsy.展开更多
基金supported by the National Natural Science Foundation of China[11635013,11705248,U1832101]National Key Research and Development Program of China[2017YFC0108605]the Science and Technology Research Project of Gansu Province[No.145RTSA012 and 17JR5RA307]。
文摘Objective To obtain precise data on the changes in the levels of 29 cytokines in mice after high or low linear energy transfer(LET)irradiation and to develop an accurate model of radiation exposure based on the cytokine levels after irradiation.Methods Plasma samples harvested from mice at different time points after carbon-ion or X-ray irradiation were analyzed using meso-scale discovery(MSD),a high-throughput and sensitive electrochemiluminescence measurement technique.Dose estimation equations were set up using multiple linear regression analysis.Results The relative levels of IL-6 at 1 h,IL-5 and IL-6 at 24 h,and IL-5,IL-6 and IL-15 at 7 d after irradiation with two intensities increased dose-dependently.The minimum measured levels of IL-5,IL-6 and IL-15 were up to 4.0076 pg/mL,16.4538 pg/mL and 0.4150 pg/mL,respectively.In addition,dose estimation models were established and verified.Conclusions The MSD assay can provide more accurate data regarding the changes in the levels of the cytokines IL-5,IL-6 and IL-15.These cytokines could meet the essential criteria for radiosensitive biomarkers and can be used as radiation indicators.Our prediction models can conveniently and accurately estimate the exposure dose in irradiated organism.
文摘AIM: To investigate if an immune imbalance may account for the development and progression of chronic radiation enteritis. We analyzed the Th1/Th2 immune response profile early and 6 mo after fractionated colorectal irradiation. METHODS: A rat model of fractionated colorectal γ-irradiation (4-Gy fractions, 3 fractions per week) was designed to investigate the effects of cumulative dose on inflammatory mediators (cytokines and chemo- kines) and immune response (Th1/Th2 profile and immunosuppressive mediator IL-10) during acute (early) response and 6 mo after the end of fractionated irradiation (chronic response). Analyses were performed 1 d after the cumulative doses of 16 Gy and 36 Gy and 1 d, 3 d, and 26 wk after the cumulative dose of 52 Gy. RESULTS: Without causing histological damage, fractionated radiation induced elevated expression of IL-1β, TNFα, MCP-1, and iNOS in distal colonic mucosa during the early post-irradiation phase. At that time, a Th2 profile was confirmed by expression of both the Th2- specific transcription factor GATA-3 and the chemokine receptor CCR4 and by suppression of the Thl cytokine IFNγ/IP-10 throughout the irradiation protocol. After 6 mo, despite the 2-fold reduction of iNOS and MCP-1 levels, the Th2 profile persisted, as shown by a 50% reduction in the expression of the Thl transcription factor T-bet, the chemokine receptor CCXCR3, and the IFNγ/ STAT1 pathway. At the same time-point, the immunosuppressive IL-10/STAT3 pathway, known to regulate the Th1/Th2 balance, was expressed, in irradiated rats, at approximately half its level as compared to controls.This suppression was associated with an overexpression of SOCS3, which inhibits the feedback of the Thl polarization and regulates IL-10 production. CONCLUSION: Colorectal irradiation induces Th2 polarization, defective IL-10/STAT3 pathway activation and SOCS3 overexpression. These changes, in turn, maintain a immunological imbalance that persists in the long term.
文摘AIM: To investigate their expression and activity in the rat ileum after exposure to ionizing radiation along with that of the cellular effectors and molecular mediators involved in the regulation of MMPs. METHODS: Rats were exposed to a single 10-Gy dose of X-rays delivered to the abdomen. A combination of methods, such as zymography, immunohistochemistry and real time reverse transcriptase-polymerase chain reaction, were used to localize and quantify MMPs and the molecules involved in MMP activating and inhibitory pathways (plasmin/ plasminogen, TIMPs), CD^8+, as well as inflammatory (interleukin (IL)-1β, IL-8, tumor necrosis factor-s, TNF-α) and fibrogenic mediators (transforming growth factor- β1-3) within ileal tissue at 1, 3, and 7 d after irradiation. RESULTS: A marked increase in MMP-2 and -14 mRNA and protein levels associated with an increased activity of MMP-2 was observed in irradiated ileal tissue. MMP-2 and -14 expression was mainly observed in inflammatory, epithelial, and mesenchymal cells, whereas a slight increase in MMP-3 expression was detected in the few infiltrating macrophages at d i after irradiation. Conversely, MMP-1, -7, and -9 mRNA levels were not found to be affected by abdominal irradiation. Irradiation was found to induce disappearance of CD^8+ cells. Furthermore, we have observed that TNF-α and IL-1β protein levels increased 6 h after irradiation, whereas those of IL-8 only increased after 3 d and was concomitant with neutrophil infiltration. In addition, the expressions of molecules involved in MMP activating and inhibitory pathways (urokinase-type plasminogen activator andtissue-type plasminogen activator; TIMP-1, TIMP-2, and plasminogen activator-inhibitor-i) were found to be increased after abdominal irradiation. CONCLUSION: This study showed that abdominal irradiation induces an acute remodeling of the ileum associated with an increased expression of MMPs and TIMPs that do not involve CD^8+ T cells but involve mesenchymal and epithelial cells, although to a lesser extent, and probably even soluble inflammatory and fibrogenic mediators.
基金supported by the Research Fund of Hanyang University(HY-2012)
文摘To investigate a possible therapeutic mechanism of cell therapy in the field of cerebral palsy using granulocyte-colony stimulating factor(G-CSF)-mobilized peripheral blood mononuclear cells(m PBMCs),we compared the expression of inflammatory cytokines and neurotrophic factors in PBMCs and m PBMCs from children with cerebral palsy to those from healthy adult donors and to cord blood mononuclear cells donated from healthy newborns.No significant differences in expression of neurotrophic factors were found between PBMCs and m PBMCs.However,in cerebral palsy children,the expression of interleukin-6 was significantly increased in m PBMCs as compared to PBMCs,and the expression of interleukin-3 was significantly decreased in m PBMCs as compared to PBMCs.In healthy adults,the expression levels of both interleukin-1βand interleukin-6 were significantly increased in m PBMCs as compared to PBMCs.The expression of brain-derived neurotrophic factors in m PBMC from cerebral palsy children was significantly higher than that in the cord blood or m PBMCs from healthy adults.The expression of G-CSF in m PBMCs from cerebral palsy children was comparable to that in the cord blood but significantly higher than that in m PBMCs from healthy adults.Lower expression of pro-inflammatory cytokines(interleukin-1β,interleukin-3,and-6)and higher expression of anti-inflammatory cytokines(interleukin-8 and interleukin-9)were observed from the cord blood and m PBMCs from cerebral palsy children rather than from healthy adults.These findings indicate that m PBMCs from cerebral palsy and cord blood mononuclear cells from healthy newborns have the potential to become seed cells for treatment of cerebral palsy.