Spinal cord injury （SCI） is a devastating type of neurological trauma with limited therapeutic op- portunities. The pathophysiology of SCI involves primary and secondary mechanisms of injury. Among all the secondary...Spinal cord injury （SCI） is a devastating type of neurological trauma with limited therapeutic op- portunities. The pathophysiology of SCI involves primary and secondary mechanisms of injury. Among all the secondary injury mechanisms, the inflammatory response is the major contrib- utor and results in expansion of the lesion and further loss of neurologic function. Meanwhile, the inflammation directly and indirectly dominates the outcomes of SCI, including not only pain and motor dysfunction, but also preventingneuronal regeneration. Microglia and macrophages play very important roles in secondary injury. Microglia reside in spinal parenchyma and survey the microenvironment through the signals of injury or infection. Macrophages are derived from monocytes recruited to injured sites from the peripheral circulation. Activated resident microglia and monocyte-derived macrophages induce and magnify immune and inflammatory responses not only by means of their secretory moleculesand phagocytosis, but also through their influence on astrocytes, oligodendrocytes and demyelination. In this review, we focus on the roles of mi- croglia and macrophages in secondary injury and how they contribute to the sequelae of SCI.展开更多
AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated fro...AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.展开更多
AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in...AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in cancer and normal mucous membrane and SDF-1 mRNA in lymph nodes around the stomach was detected using quantitative polymerase chain reaction (PCR) (TaqMan) and immunohistochemistric assay.SGC-7901 and MGC80-3 cancer cells were used to investigate the effect of SDF-1 on cell proliferation and migration.RESULTS:Quantitative reverse transcription PCR and immunohistochemistry revealed that the expression level of CXCR4 in gastric cancer was significantly higher than that in normal mucous membrane (1.6244 ± 1.3801 vs 1.0715 ± 0.5243,P < 0.05).The expression level of CXCR4 mRNA in gastric cancer with lymph node metastasis was also significantly higher than that without lymph node metastasis (0.823 ± 0.551 vs 0.392 ± 0.338,P < 0.05).CXCR4 expression was significantly related to poorly differentiated,high tumor stage and lymph node metastasis.Significant differences in the expression level of SDF-1 mRNA were found between lymph nodes in metastatic gastric cancer and normal nodes (0.5432 ± 0.4907 vs 0.2640 ± 0.2601,P < 0.05).The positive expression of SDF-1 mRNA in lymph nodes of metastatic gastric cancer was consistent with the positive expression of CXCR4 mRNA in gastric cancer (r=0.776,P < 0.01).Additionally,human gastric cancer cell lines expressed CXCR4 and showed vigorous proliferation and migratory responses to SDF-1.AMD3100 (a specific CXCR4 antagonist) was also found to effectively reduce the migration of gastric cancer cells.CONCLUSION:The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer.CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.展开更多
AIM： To evaluate and compare the expression profiles of CXCL12 （SDF-1）, CCL19 （MIP-3β）, CCL20 （MIP-3a） and CCL21 （6Ckine, Exodus2） and their receptors on RNA and protein levels in hepatocellular carcinoma （...AIM： To evaluate and compare the expression profiles of CXCL12 （SDF-1）, CCL19 （MIP-3β）, CCL20 （MIP-3a） and CCL21 （6Ckine, Exodus2） and their receptors on RNA and protein levels in hepatocellular carcinoma （HCC） versus colorectal liver metastases （CRLM） and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases. METHODS： Chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent nontumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RT- PCR and Western blot analysis in the same cases of HCC and CRLM. RESULTS： Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20 demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly up-regulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues. CONCLUSION： Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked up-regulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.展开更多
基金supported by grants from National Institutes of Health(R01GM100474)the New Jersey Commission on Spinal Cord Research(CSCR13IRG006)
文摘Spinal cord injury （SCI） is a devastating type of neurological trauma with limited therapeutic op- portunities. The pathophysiology of SCI involves primary and secondary mechanisms of injury. Among all the secondary injury mechanisms, the inflammatory response is the major contrib- utor and results in expansion of the lesion and further loss of neurologic function. Meanwhile, the inflammation directly and indirectly dominates the outcomes of SCI, including not only pain and motor dysfunction, but also preventingneuronal regeneration. Microglia and macrophages play very important roles in secondary injury. Microglia reside in spinal parenchyma and survey the microenvironment through the signals of injury or infection. Macrophages are derived from monocytes recruited to injured sites from the peripheral circulation. Activated resident microglia and monocyte-derived macrophages induce and magnify immune and inflammatory responses not only by means of their secretory moleculesand phagocytosis, but also through their influence on astrocytes, oligodendrocytes and demyelination. In this review, we focus on the roles of mi- croglia and macrophages in secondary injury and how they contribute to the sequelae of SCI.
文摘AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.
基金Supported by The National Natural Science Foundation of China, No. 30772542
文摘AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in cancer and normal mucous membrane and SDF-1 mRNA in lymph nodes around the stomach was detected using quantitative polymerase chain reaction (PCR) (TaqMan) and immunohistochemistric assay.SGC-7901 and MGC80-3 cancer cells were used to investigate the effect of SDF-1 on cell proliferation and migration.RESULTS:Quantitative reverse transcription PCR and immunohistochemistry revealed that the expression level of CXCR4 in gastric cancer was significantly higher than that in normal mucous membrane (1.6244 ± 1.3801 vs 1.0715 ± 0.5243,P < 0.05).The expression level of CXCR4 mRNA in gastric cancer with lymph node metastasis was also significantly higher than that without lymph node metastasis (0.823 ± 0.551 vs 0.392 ± 0.338,P < 0.05).CXCR4 expression was significantly related to poorly differentiated,high tumor stage and lymph node metastasis.Significant differences in the expression level of SDF-1 mRNA were found between lymph nodes in metastatic gastric cancer and normal nodes (0.5432 ± 0.4907 vs 0.2640 ± 0.2601,P < 0.05).The positive expression of SDF-1 mRNA in lymph nodes of metastatic gastric cancer was consistent with the positive expression of CXCR4 mRNA in gastric cancer (r=0.776,P < 0.01).Additionally,human gastric cancer cell lines expressed CXCR4 and showed vigorous proliferation and migratory responses to SDF-1.AMD3100 (a specific CXCR4 antagonist) was also found to effectively reduce the migration of gastric cancer cells.CONCLUSION:The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer.CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.
文摘AIM： To evaluate and compare the expression profiles of CXCL12 （SDF-1）, CCL19 （MIP-3β）, CCL20 （MIP-3a） and CCL21 （6Ckine, Exodus2） and their receptors on RNA and protein levels in hepatocellular carcinoma （HCC） versus colorectal liver metastases （CRLM） and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases. METHODS： Chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent nontumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RT- PCR and Western blot analysis in the same cases of HCC and CRLM. RESULTS： Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20 demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly up-regulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues. CONCLUSION： Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked up-regulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.
