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10.3389/fimmu.2018.00537 http://scihub22266oqcxt.onion/10.3389/fimmu.2018.00537 C5879126!5879126 !29632528     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29632528 &cmd=llinks): Failed to open stream: HTTP request failed! 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PKC?-Mediated Nox2 Activation Promotes Fluid-Phase Pinocytosis of Antigens by Immature Dendritic Cells |pdf=|usr=}}{{29632528 }} gab.com Text PKC -Mediated Nox2 Activation Promotes Fluid-Phase Pinocytosis of Antigens by Immature Dendritic Cells JO: Front Immunol http://www.kidney.de/pget.php?&tw=1&pmid=29632528 #FOAvip AIMS: Macropinocytosis is a major endocytic pathway by which dendritic cells (DCs) internalize antigens in the periphery. Despite the importance of DCs in the initiation and control of adaptive immune responses, the signaling mechanisms mediating DC macropinocytosis of antigens remain largely unknown. The goal of the present study was to investigate whether protein kinase C (PKC) is involved in stimulation of DC macropinocytosis and, if so, to identify the specific PKC isoform(s) and downstream signaling mechanisms involved. METHODS: Various cellular, molecular and immunological techniques, pharmacological approaches and genetic knockout mice were utilized to investigate the signaling mechanisms mediating DC macropinocytosis. RESULTS: Confocal laser scanning microscopy confirmed that DCs internalize fluorescent antigens (ovalbumin) using macropinocytosis. Pharmacological blockade of classical and novel PKC isoforms using calphostin C abolished both phorbol ester- and hepatocyte growth factor-induced antigen macropinocytosis in DCs. The qRT-PCR experiments identified PKC? as the dominant PKC isoform in DCs. Genetic studies demonstrated the functional role of PKC? in DC macropinocytosis of antigens, their subsequent maturation, and secretion of various T-cell stimulatory cytokines, including IL-1?, TNF-? and IFN-?. Additional mechanistic studies identified NADPH oxidase 2 (Nox2) and intracellular superoxide anion as important players in DC macropinocytosis of antigens downstream of PKC? activation. CONCLUSION: The findings of the present study demonstrate a novel mechanism by which PKC? activation via stimulation of Nox2 activity and downstream redox signaling promotes DC macropinocytosis of antigens. PKC?/Nox2-mediated antigen macropinocytosis stimulates maturation of DCs and secretion of T-cell stimulatory cytokines. These findings may contribute to a better understanding of the regulatory mechanisms in DC macropinocytosis and downstream regulation of T-cell-mediated responses. Twit Text FOAVip PKC -Mediated Nox2 Activation Promotes Fluid-Phase Pinocytosis of Antigens by Immature Dendritic Cells ????Front Immunol http://www.kidney.de/pget.php?&tw=1&pmid=29632528 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29632528 #FOAvip English Wikipedia <ref>{{Cite pmid|29632528 }}</ref> PKC?-Mediated Nox2 Activation Promotes Fluid-Phase Pinocytosis of Antigens by Immature Dendritic Cells #MMPMID29632528 Singla B ; Ghoshal P ; Lin H ; Wei Q ; Dong Z ; Csányi G Front Immunol 2018[]; 9 (ä): 537 PMID29632528 show ga AIMS: Macropinocytosis is a major endocytic pathway by which dendritic cells (DCs) internalize antigens in the periphery. Despite the importance of DCs in the initiation and control of adaptive immune responses, the signaling mechanisms mediating DC macropinocytosis of antigens remain largely unknown. The goal of the present study was to investigate whether protein kinase C (PKC) is involved in stimulation of DC macropinocytosis and, if so, to identify the specific PKC isoform(s) and downstream signaling mechanisms involved. METHODS: Various cellular, molecular and immunological techniques, pharmacological approaches and genetic knockout mice were utilized to investigate the signaling mechanisms mediating DC macropinocytosis. RESULTS: Confocal laser scanning microscopy confirmed that DCs internalize fluorescent antigens (ovalbumin) using macropinocytosis. Pharmacological blockade of classical and novel PKC isoforms using calphostin C abolished both phorbol ester- and hepatocyte growth factor-induced antigen macropinocytosis in DCs. The qRT-PCR experiments identified PKC? as the dominant PKC isoform in DCs. Genetic studies demonstrated the functional role of PKC? in DC macropinocytosis of antigens, their subsequent maturation, and secretion of various T-cell stimulatory cytokines, including IL-1?, TNF-? and IFN-?. Additional mechanistic studies identified NADPH oxidase 2 (Nox2) and intracellular superoxide anion as important players in DC macropinocytosis of antigens downstream of PKC? activation. CONCLUSION: The findings of the present study demonstrate a novel mechanism by which PKC? activation via stimulation of Nox2 activity and downstream redox signaling promotes DC macropinocytosis of antigens. PKC?/Nox2-mediated antigen macropinocytosis stimulates maturation of DCs and secretion of T-cell stimulatory cytokines. These findings may contribute to a better understanding of the regulatory mechanisms in DC macropinocytosis and downstream regulation of T-cell-mediated responses. |*Pinocytosis [MESH] |Animals [MESH] |Antigens [MESH] |Cytokines/physiology [MESH] |Dendritic Cells/*physiology [MESH] |Male [MESH] |Mice, Inbred C57BL [MESH] |Mice, Knockout [MESH] |NADPH Oxidase 2/*physiology [MESH] |Ovalbumin [MESH]PKC?-Mediated Nox2 Activation Promotes Fluid-Phase Pinocytosis of Anti(epmc).pdf DeepDyve Pubget Overpricing