Cudrania tricuspidata Bureau (CTB) is one of the Korean herbal plants and has been used traditionally for treating tumor, gastritis, liver damage, and inflammation in Korea. Recently, many researchers have tried to find bioactive compounds having immunopharmacological ability from natural sources an...
Cudrania tricuspidata Bureau (CTB) is one of the Korean herbal plants and has been used traditionally for treating tumor, gastritis, liver damage, and inflammation in Korea. Recently, many researchers have tried to find bioactive compounds having immunopharmacological ability from natural sources and to investigate a possible therapeutic application of traditional medicines in allergic disease, because compounds of natural products do not have cytotoxicity and side effects onto body tissues. From this standpoint, this study was carried out to investigate the immunomodultory role of a glycoprotein isolated from CTB (CTB glycoprotein, 75 kDa) in immune cells and in vivo. Di(2-ethylhexyl) phthalate (DEHP) is an environmental chemical used in polyvinyl chloride (PVC) products including vinyl flooring, and children?s toys that displays an allergic inflammatory potential in human and animals. Moreover, concerning about allergic potential of environmental chemicals among children has been steadily increased. Allergic immune response is a hypersensitive reaction that is characterized by predominant T helper type 2 (Th2) response, immunoglobulin (Ig)E production from B lymphocytes, and activation of mast cells through cross-linking of antigen and IgE/Fc?RI complex. So far, this study has focused the immunomodulatory function of the CTB glycoprotein on T lymphocytes, B lymphocytes, and mast cells by stages. In the present study, the results showed that the CTB glycoprotein contributes to the inhibition of Th2 response, B lymphocytes proliferation, and mast cell activation caused by DEHP. For inhibitory activity of the CTB glycoprotein on Th2 response, the results showed that 100 ?g/ml of CTB glycoprotein has inhibitory effects on the production of intracellular ROS, the activities of p38 mitogen-activated protein kinase (MAPK) and GATA-binding protein 3 (GATA 3), and the expressions of interleukin (IL)-4 and IL-10 induced by DEHP in thymocytes. For anti-proliferative activity of the CTB glycoprotein, the results indicated that the CTB glycoprotein has dose-dependent blocking effects on the expressions of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin-dependent kinase (CDK)-4 in B lymphocytes. Furthermore, the CTB glycoprotein reduces Ca2+ level, activations of PKC/MAPK, NF-?B, cyclin D1, and CDK-4 in DEHP-treated cells. The activation of NF-?B was collectively blocked by pretreatment with PKC inhibitor (staurosporine) and ERK1/2 inhibitor (PD98059), respectively. For anti-inflammatory activity of the CTB glycoprotein, the results revealed that the CTB glycoprotein has dose dependent suppressive effects on DEHP-induced degranulation of mast cells in RBL-2H3 cells. The results showed that the CTB glycoprotein in the presence of DEHP inhibits the release of histamine and arachidonic acid, and expressions of cyclooxygenase (COX)-2, interleukin (IL)-4, IL-6, and TNF-? in RBL-2H3 cells. It has been found that the CTB glycoprotein inhibits the intracellular Ca2+ level, translocation of PKC from cytosol to membrane and the phosphorylation of ERK1/2 in cells. Moreover, the CTB glycoprotein (100 ?g/ml) has suppressive effects on transcriptional activation of NF-?B in DEHP-treated RBL-2H3 cells. The activation of NF-?B was collectively blocked by treatment with PKC inhibitor (staurosporine) as well as ERK1/2 inhibitor (PD98059), respectively. For anti-allergic inflammatory property of the CTB glycoprotein, the results showed that the CTB glycoprotein has dose-dependent inhibitory effects either on compound 48/80- or DEHP-mediated allergic inflammatory factors in mice. The results showed that 10 mg/kg CTB glycoprotein in the presence of DEHP inhibits the activity of ?-hexosaminidase, and production of IgE and IL-4 in mice. From obtained findings, the CTB glycoprotein exerts its anti-oxidative, anti-proliferative, and anti-inflammatory properties via modulation of MAPK phosphorylation and inflammation-related factors in immune cells and in vivo. Especially, their inhibitory action was deduced from down-regulation of ERK1/2 and p38 MAPK phosphorylation on the each stage in the present study, thereby suppressing allergic inflammatory mediators including IL-4, -6, -10, TNF-?, and IgE in cells and mice. As investigate those signaling pathway in an allergic inflammatory response evoked by DEHP, it may constitute a novel therapeutic approach for the treatment and prevention of allergy-related immune diseases.
Cudrania tricuspidata Bureau (CTB) is one of the Korean herbal plants and has been used traditionally for treating tumor, gastritis, liver damage, and inflammation in Korea. Recently, many researchers have tried to find bioactive compounds having immunopharmacological ability from natural sources and to investigate a possible therapeutic application of traditional medicines in allergic disease, because compounds of natural products do not have cytotoxicity and side effects onto body tissues. From this standpoint, this study was carried out to investigate the immunomodultory role of a glycoprotein isolated from CTB (CTB glycoprotein, 75 kDa) in immune cells and in vivo. Di(2-ethylhexyl) phthalate (DEHP) is an environmental chemical used in polyvinyl chloride (PVC) products including vinyl flooring, and children?s toys that displays an allergic inflammatory potential in human and animals. Moreover, concerning about allergic potential of environmental chemicals among children has been steadily increased. Allergic immune response is a hypersensitive reaction that is characterized by predominant T helper type 2 (Th2) response, immunoglobulin (Ig)E production from B lymphocytes, and activation of mast cells through cross-linking of antigen and IgE/Fc?RI complex. So far, this study has focused the immunomodulatory function of the CTB glycoprotein on T lymphocytes, B lymphocytes, and mast cells by stages. In the present study, the results showed that the CTB glycoprotein contributes to the inhibition of Th2 response, B lymphocytes proliferation, and mast cell activation caused by DEHP. For inhibitory activity of the CTB glycoprotein on Th2 response, the results showed that 100 ?g/ml of CTB glycoprotein has inhibitory effects on the production of intracellular ROS, the activities of p38 mitogen-activated protein kinase (MAPK) and GATA-binding protein 3 (GATA 3), and the expressions of interleukin (IL)-4 and IL-10 induced by DEHP in thymocytes. For anti-proliferative activity of the CTB glycoprotein, the results indicated that the CTB glycoprotein has dose-dependent blocking effects on the expressions of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin-dependent kinase (CDK)-4 in B lymphocytes. Furthermore, the CTB glycoprotein reduces Ca2+ level, activations of PKC/MAPK, NF-?B, cyclin D1, and CDK-4 in DEHP-treated cells. The activation of NF-?B was collectively blocked by pretreatment with PKC inhibitor (staurosporine) and ERK1/2 inhibitor (PD98059), respectively. For anti-inflammatory activity of the CTB glycoprotein, the results revealed that the CTB glycoprotein has dose dependent suppressive effects on DEHP-induced degranulation of mast cells in RBL-2H3 cells. The results showed that the CTB glycoprotein in the presence of DEHP inhibits the release of histamine and arachidonic acid, and expressions of cyclooxygenase (COX)-2, interleukin (IL)-4, IL-6, and TNF-? in RBL-2H3 cells. It has been found that the CTB glycoprotein inhibits the intracellular Ca2+ level, translocation of PKC from cytosol to membrane and the phosphorylation of ERK1/2 in cells. Moreover, the CTB glycoprotein (100 ?g/ml) has suppressive effects on transcriptional activation of NF-?B in DEHP-treated RBL-2H3 cells. The activation of NF-?B was collectively blocked by treatment with PKC inhibitor (staurosporine) as well as ERK1/2 inhibitor (PD98059), respectively. For anti-allergic inflammatory property of the CTB glycoprotein, the results showed that the CTB glycoprotein has dose-dependent inhibitory effects either on compound 48/80- or DEHP-mediated allergic inflammatory factors in mice. The results showed that 10 mg/kg CTB glycoprotein in the presence of DEHP inhibits the activity of ?-hexosaminidase, and production of IgE and IL-4 in mice. From obtained findings, the CTB glycoprotein exerts its anti-oxidative, anti-proliferative, and anti-inflammatory properties via modulation of MAPK phosphorylation and inflammation-related factors in immune cells and in vivo. Especially, their inhibitory action was deduced from down-regulation of ERK1/2 and p38 MAPK phosphorylation on the each stage in the present study, thereby suppressing allergic inflammatory mediators including IL-4, -6, -10, TNF-?, and IgE in cells and mice. As investigate those signaling pathway in an allergic inflammatory response evoked by DEHP, it may constitute a novel therapeutic approach for the treatment and prevention of allergy-related immune diseases.
주제어
#allergy-related immune diseases
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