AIM： To investigate how macrophage inducible C-type lectin（Mincle） influences inflammation in mice fungal keratitis induced by Aspergillus fumigatus（A. fumigatus）.METHODS： C57 BL/6 mice were infected with A. fum...AIM： To investigate how macrophage inducible C-type lectin（Mincle） influences inflammation in mice fungal keratitis induced by Aspergillus fumigatus（A. fumigatus）.METHODS： C57 BL/6 mice were infected with A. fumigatus after pretreated with Mincle agonist TDB or Mincle neutralizing antibody（MincleAb）, taking DMSO or IgG as control group respectively. The cornea lesions were monitored with slit-lamp microscope and evaluated by clinical score. Mincle expression was assessed using reverse transcriptionploymerase chain reaction（RT-PCR） and immunostaining. The expression of cytokines（IL-1β, TNF-α and IL-6） chemokines（CXCL-1 and MIP-2） was determined by RTPCR and ELISA. Neutrophil infiltration was observed by immunostaining. The levels of nitric oxide（NO） generated by corneas were tested by Griess reaction. RESULTS： Mincle mRNA and protein levels were higher in infected corneas than normal corneas of C57 BL/6 mice, saving clinical scores revealed differences. When pretreated with Mincle agonist TDB, the mRNA and protein levels of IL-1β, TNF-α and IL-6 in infected corneas were significantly increased compared with the control group（P〈0.01）. Results of the counterpart in corneas pretreated with Mincle neutralizing antibody was decreased consistently（P〈0.01）. Expression of CXCL1 and MIP-2 mRNA levels were upregulated in TDB group and down-regulated in Mincle Ab group（P〈0.01）, coincide with neutrophil aggregation degree in corneas showed by immunostaining. As for the concentration of NO, it was promoted in TDB group compared with DMSO control group, and decreased in Mincle Ab group compared with Ig G control group.CONCLUSION： Mincle plays a dual role in mice fungal keratitis. It participates in the innate immune system by enhancing inflammation. What＇s more, Mincle can mediate cytotoxic effects by regulating the formation of NO.展开更多
The development of novel adjuvants constitutes a new strategy for the research of tumor vaccines.Immunomodulatory molecule adjuvants are one of the novel adjuvants that can effectively stimulate the pattern recognitio...The development of novel adjuvants constitutes a new strategy for the research of tumor vaccines.Immunomodulatory molecule adjuvants are one of the novel adjuvants that can effectively stimulate the pattern recognition receptors to activate the downstream pathways of immune cells.However,there are few studies on immunomodulatory molecular adjuvants associated with C-type lectin.It has been reported that GlcC_(14)C_(18)is a Mincle ligand with a relatively simple structure and strong adjuvant activity in vivo.Herein,we coupled GlcC_(14)C_(18)with MUC1 glycopeptide and evaluated its immune effect.In addition,we also synthesized α-GlcC_(14)C_(18)-MUC1 and β-GlcC_(14)C_(18)-MUC1 based on the two configurations of GlcC_14C_(18)and compared their immune effects.The results show that both of the two configurations of the vaccine have a good immune effect,but to a certain extent,the immune effect of β-GlcC_(14)C_(18)-MUC1 is better than that of α-GlcC_(14)C_(18)-MUC1.展开更多
Inflammation plays an important role in nerve defects caused by intracerebral hemorrhage. Repairing brain damage by inhibiting the macrophage-inducible C-type lectin/spleen tyrosine kinase （Mincle/Syk） signaling pat...Inflammation plays an important role in nerve defects caused by intracerebral hemorrhage. Repairing brain damage by inhibiting the macrophage-inducible C-type lectin/spleen tyrosine kinase （Mincle/Syk） signaling pathway is a potential new target for treating cerebral hemorrhage. In this study, we aimed to determine whether acupuncture through Baihui （DU20） to Qubin （GBT） is an effective treatment for intracerebral hemorrhage through the Mincle/Syk signaling pathway. An intracerebral hemorrhage rat model was established by autol- ogous blood infusion into the caudate nucleus. Acupuncture through Baihui to Qubin was performed for 30 minutes, once every 12 hours, for a total of three times. Piceatannol （34.62 mg/kg）, a Syk inhibitor, was intraperitoneally injected as a control. Modified neurological severity score was used to assess neurological function. Brain water content was measured. Immunohistochemistry and western blot assay were used to detect immunoreactivity and protein expression levels of Minde, Syk, and CARD9. Real-time polymerase chain reaction was used to determine interleukin-1[~ mRNA levels. Hematoxylin-eosin staining was performed to observe histopathological changes. Our re- suits showed that acupuncture through Baihui to Qubin remarkably improved neurological function and brain water content, and inhibited immunoreactivity and expression of Mincle, Syk, CARDg, and interkeukin-1β Moreover, this effect was similar to piceatannol. These find- ings suggest that acupuncture through Baihui to Qubin can improve neurological impairment after cerebral hemorrhage by inhibiting the Mincle/Syk signaling pathway.展开更多
基金Supported by the National Natural Science Foundation of China(No.81470609No.81500695)
文摘AIM： To investigate how macrophage inducible C-type lectin（Mincle） influences inflammation in mice fungal keratitis induced by Aspergillus fumigatus（A. fumigatus）.METHODS： C57 BL/6 mice were infected with A. fumigatus after pretreated with Mincle agonist TDB or Mincle neutralizing antibody（MincleAb）, taking DMSO or IgG as control group respectively. The cornea lesions were monitored with slit-lamp microscope and evaluated by clinical score. Mincle expression was assessed using reverse transcriptionploymerase chain reaction（RT-PCR） and immunostaining. The expression of cytokines（IL-1β, TNF-α and IL-6） chemokines（CXCL-1 and MIP-2） was determined by RTPCR and ELISA. Neutrophil infiltration was observed by immunostaining. The levels of nitric oxide（NO） generated by corneas were tested by Griess reaction. RESULTS： Mincle mRNA and protein levels were higher in infected corneas than normal corneas of C57 BL/6 mice, saving clinical scores revealed differences. When pretreated with Mincle agonist TDB, the mRNA and protein levels of IL-1β, TNF-α and IL-6 in infected corneas were significantly increased compared with the control group（P〈0.01）. Results of the counterpart in corneas pretreated with Mincle neutralizing antibody was decreased consistently（P〈0.01）. Expression of CXCL1 and MIP-2 mRNA levels were upregulated in TDB group and down-regulated in Mincle Ab group（P〈0.01）, coincide with neutrophil aggregation degree in corneas showed by immunostaining. As for the concentration of NO, it was promoted in TDB group compared with DMSO control group, and decreased in Mincle Ab group compared with Ig G control group.CONCLUSION： Mincle plays a dual role in mice fungal keratitis. It participates in the innate immune system by enhancing inflammation. What＇s more, Mincle can mediate cytotoxic effects by regulating the formation of NO.
基金supported by the National Natural Science Foundation of China (Nos. 22077068, 82103984)the Fundamental Research Funds for the Central Universities。
文摘The development of novel adjuvants constitutes a new strategy for the research of tumor vaccines.Immunomodulatory molecule adjuvants are one of the novel adjuvants that can effectively stimulate the pattern recognition receptors to activate the downstream pathways of immune cells.However,there are few studies on immunomodulatory molecular adjuvants associated with C-type lectin.It has been reported that GlcC_(14)C_(18)is a Mincle ligand with a relatively simple structure and strong adjuvant activity in vivo.Herein,we coupled GlcC_(14)C_(18)with MUC1 glycopeptide and evaluated its immune effect.In addition,we also synthesized α-GlcC_(14)C_(18)-MUC1 and β-GlcC_(14)C_(18)-MUC1 based on the two configurations of GlcC_14C_(18)and compared their immune effects.The results show that both of the two configurations of the vaccine have a good immune effect,but to a certain extent,the immune effect of β-GlcC_(14)C_(18)-MUC1 is better than that of α-GlcC_(14)C_(18)-MUC1.
基金supported by the National Natural Science Foundation of China,No.81473764,81273824the Key Project of Natural Science Foundation of Heilongjiang Province of China,No.ZD201204the Doctoral Fund Program of Ministry of Education of China,No.20102327110003
文摘Inflammation plays an important role in nerve defects caused by intracerebral hemorrhage. Repairing brain damage by inhibiting the macrophage-inducible C-type lectin/spleen tyrosine kinase （Mincle/Syk） signaling pathway is a potential new target for treating cerebral hemorrhage. In this study, we aimed to determine whether acupuncture through Baihui （DU20） to Qubin （GBT） is an effective treatment for intracerebral hemorrhage through the Mincle/Syk signaling pathway. An intracerebral hemorrhage rat model was established by autol- ogous blood infusion into the caudate nucleus. Acupuncture through Baihui to Qubin was performed for 30 minutes, once every 12 hours, for a total of three times. Piceatannol （34.62 mg/kg）, a Syk inhibitor, was intraperitoneally injected as a control. Modified neurological severity score was used to assess neurological function. Brain water content was measured. Immunohistochemistry and western blot assay were used to detect immunoreactivity and protein expression levels of Minde, Syk, and CARD9. Real-time polymerase chain reaction was used to determine interleukin-1[~ mRNA levels. Hematoxylin-eosin staining was performed to observe histopathological changes. Our re- suits showed that acupuncture through Baihui to Qubin remarkably improved neurological function and brain water content, and inhibited immunoreactivity and expression of Mincle, Syk, CARDg, and interkeukin-1β Moreover, this effect was similar to piceatannol. These find- ings suggest that acupuncture through Baihui to Qubin can improve neurological impairment after cerebral hemorrhage by inhibiting the Mincle/Syk signaling pathway.
