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Gerelchuluun, Turmunkh,Lee, Young-Hee,Lee, Young-Ran,Im, Sun-A,Song, Suk-Gil,Park, Jeong-Sook,Han, Kun,Kim, Kyung-Jae,Lee, Chong-Kil 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.11
Biodegradable nanospheres generated from a biocompatible polymer, poly(D,L-lactide-co-glycolide) (PLGA), have been studied extensively as implantable reservoirs for sustained-release drug delivery. PLGA-nanospheres have also been studied as vehicles to deliver antigens to phagocytes. The intracellular ar processing pathway of antigens delivered to phagocytes by PLGA particles was studied in the present study. Ovalbumin (OVA) encapsulated with PLGA (OVA-nanosphere) was efficiently captured, processed and presented on class I major histocompatibility complex (MHC-I) by dendritic cells (DCs). The MHC-I processing of OVA-nano-spheres was resistant to lactacystin, a proteosome inhibitor, and brefeldin A, which blocks anterograde transport from the endoplasmic reticulum (ER) through the Golgi apparatus. Chloroquine, which inhibits phagolysosomal enzymes by increasing ph ago lysosomal pH, inhibited MHC-I processing of OVA-nanospheres. In addition, DCs generated from TAP-/- mice were markedly suppressed in MHC-I processing of OVA-nanospheres. These results demonstrate that DCs process phagocytosed OVA-nanospheres via a vacuolar alternate MHC-I pathway for presentation of OVA peptides to T lymphocytes.
Turmunkh Gerelchuluun,이영희,이영란,임선아,송석길,박정숙,한건,김경제,이종길 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.11
Biodegradable nanospheres generated from a biocompatible polymer, poly(D,L-lactide-co-glycolide) (PLGA), have been studied extensively as implantable reservoirs for sustained-release drug delivery. PLGA-nanospheres have also been studied as vehicles to deliver antigens to phagocytes. The intracellular ar processing pathway of antigens delivered to phagocytes by PLGA particles was studied in the present study. Ovalbumin (OVA) encapsulated with PLGA (OVA-nanosphere) was efficiently captured, processed and presented on class I major histocompatibility complex (MHC-I) by dendritic cells (DCs). The MHC-I processing of OVA-nano-spheres was resistant to lactacystin, a proteosome inhibitor, and brefeldin A, which blocks anterograde transport from the endoplasmic reticulum (ER) through the Golgi apparatus. Chloroquine, which inhibits phagolysosomal enzymes by increasing ph ago lysosomal pH, inhibited MHC-I processing of OVA-nanospheres. In addition, DCs generated from TAP-/- mice were markedly suppressed in MHC-I processing of OVA-nanospheres. These results demonstrate that DCs process phagocytosed OVA-nanospheres via a vacuolar alternate MHC-I pathway for presentation of OVA peptides to T lymphocytes.
Evidence for Direct Inhibition of MHC-Restricted Antigen Processing by Dexamethasone
임선아,Turmunkh Gerelchuluun,이종길 대한면역학회 2014 Immune Network Vol.14 No.6
Dexamethasone (Dex) was shown to inhibit the differentiation,maturation, and antigen-presenting function ofdendritic cells (DC) when added during DC generation ormaturation stages. Here, we examined the direct effects ofDex on MHC-restricted antigen processing. Macrophageswere incubated with microencapsulated ovalbumin (OVA) inthe presence of different concentrations of Dex for 2 h, andthe efficacy of OVA peptide presentation was evaluated usingOVA-specific CD8 and CD4 T cells. Dex inhibited bothclass I- and class II-restricted presentation of OVA to T cells;this inhibitory effect on antigen presentation was much morepotent in immature macrophages than in mature macrophages. The presentation of the exogenously added OVApeptide SIINFEKL was not blocked by Dex. In addition,short-term treatment of macrophages with Dex had no discernibleeffects on the phagocytic activity, total expressionlevels of MHC molecules or co-stimulatory molecules. Theseresults demonstrate that Dex inhibits intracellular processingevents of phagocytosed antigens in macrophages
Evidence for Direct Inhibition of MHC-Restricted Antigen Processing by Dexamethasone
Im, Sun-A,Gerelchuluun, Turmunkh,Lee, Chong-Kil The Korean Association of Immunobiologists 2014 Immune Network Vol.14 No.6
Dexamethasone (Dex) was shown to inhibit the differentiation, maturation, and antigen-presenting function of dendritic cells (DC) when added during DC generation or maturation stages. Here, we examined the direct effects of Dex on MHC-restricted antigen processing. Macrophages were incubated with microencapsulated ovalbumin (OVA) in the presence of different concentrations of Dex for 2 h, and the efficacy of OVA peptide presentation was evaluated using OVA-specific CD8 and CD4 T cells. Dex inhibited both class I- and class II-restricted presentation of OVA to T cells; this inhibitory effect on antigen presentation was much more potent in immature macrophages than in mature macrophages. The presentation of the exogenously added OVA peptide SIINFEKL was not blocked by Dex. In addition, short-term treatment of macrophages with Dex had no discernible effects on the phagocytic activity, total expression levels of MHC molecules or co-stimulatory molecules. These results demonstrate that Dex inhibits intracellular processing events of phagocytosed antigens in macrophages.
Hyunjin Kim,Kyung-Mi Cho,Turmunkh Gerelchuluun,Ji-Seon Lee,정경수,이종길 대한면역학회 2007 Immune Network Vol.7 No.4
Background: Immunomodulators enhancing MHC-restricted antigen presentation would affect many cellular immune reactions mediated by T cells or T cell products. However, modulation of MHC-restricted antigen presentation has received little attention as a target for therapeutic immunoregulation. Here, we report that lectins isolated from mushroom Fomitella fraxinea enhance MHC-restricted exogenous antigen presentation in professional antigen presenting cells (APCs). Methods: Lectins, termed FFrL, were isolated from the carpophores of Fomitella fraxinea, and its effects on the class I and class II MHC-restricted presentation of exogenous ovalbumin (OVA) were examined in mouse dendritic cells (DCs) and mouse peritoneal macrophages. The effects of FFrL on the expression of total MHC molecules and the phagocytic activity were also examined in mouse DCs. Results: DCs cultured in the presence of FFrL overnight exhibited enhanced capacity in presenting exogenous OVA in association with class I and class II MHC molecules. FFrL increased slightly the total expression levels of both class I (H-$2K^b$) and class II (I-$A^b$) MHC molecules and the phagocytic activity of DCs. Antigen presentation-enhancing activity of FFrL was also observed in macrophages isolated from mouse peritoneum. Conclusion: Lectins isolated from the carpophores of Fomitella fraxinea increase MHC-restricted exogenous antigen presentation by enhancing intracellular processing events of phagocytosed antigens.
Kim, Hyun-Jin,Cho, Kyung-Mi,Gerelchuluun, Turmunkh,Lee, Ji-Seon,Chung, Kyeong-Soo,Lee, Chong-Kil The Korean Association of Immunobiologists 2007 Immune Network Vol.7 No.4
Background: Immunomodulators enhancing MHC-restricted antigen presentation would affect many cellular immune reactions mediated by T cells or T cell products. However, modulation of MHC-restricted antigen presentation has received little attention as a target for therapeutic immunoregulation. Here, we report that lectins isolated from mushroom Fomitella fraxinea enhance MHC-restricted exogenous antigen presentation in professional antigen presenting cells (APCs). Methods: Lectins, termed FFrL, were isolated from the carpophores of Fomitella fraxinea, and its effects on the class I and class II MHC-restricted presentation of exogenous ovalbumin (OVA) were examined in mouse dendritic cells (DCs) and mouse peritoneal macrophages. The effects of FFrL on the expression of total MHC molecules and the phagocytic activity were also examined in mouse DCs. Results: DCs cultured in the presence of FFrL overnight exhibited enhanced capacity in presenting exogenous OVA in association with class I and class II MHC molecules. FFrL increased slightly the total expression levels of both class I (H-$2K^b$) and class II (I-$A^b$) MHC molecules and the phagocytic activity of DCs. Antigen presentation-enhancing activity of FFrL was also observed in macrophages isolated from mouse peritoneum. Conclusion: Lectins isolated from the carpophores of Fomitella fraxinea increase MHC-restricted exogenous antigen presentation by enhancing intracellular processing events of phagocytosed antigens.