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The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF)
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
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| Personen und Körperschaften: | , , , , , , , , , , , , , , , |
| In: | Proceedings of the National Academy of Sciences, 108, 2011, 34 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| author_facet |
Merk, Melanie Zierow, Swen Leng, Lin Das, Rituparna Du, Xin Schulte, Wibke Fan, Juan Lue, Hongqi Chen, Yibang Xiong, Huabao Chagnon, Frederic Bernhagen, Jürgen Lolis, Elias Mor, Gil Lesur, Olivier Bucala, Richard Merk, Melanie Zierow, Swen Leng, Lin Das, Rituparna Du, Xin Schulte, Wibke Fan, Juan Lue, Hongqi Chen, Yibang Xiong, Huabao Chagnon, Frederic Bernhagen, Jürgen Lolis, Elias Mor, Gil Lesur, Olivier Bucala, Richard |
|---|---|
| author |
Merk, Melanie Zierow, Swen Leng, Lin Das, Rituparna Du, Xin Schulte, Wibke Fan, Juan Lue, Hongqi Chen, Yibang Xiong, Huabao Chagnon, Frederic Bernhagen, Jürgen Lolis, Elias Mor, Gil Lesur, Olivier Bucala, Richard |
| spellingShingle |
Merk, Melanie Zierow, Swen Leng, Lin Das, Rituparna Du, Xin Schulte, Wibke Fan, Juan Lue, Hongqi Chen, Yibang Xiong, Huabao Chagnon, Frederic Bernhagen, Jürgen Lolis, Elias Mor, Gil Lesur, Olivier Bucala, Richard Proceedings of the National Academy of Sciences The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) Multidisciplinary |
| author_sort |
merk, melanie |
| spelling |
Merk, Melanie Zierow, Swen Leng, Lin Das, Rituparna Du, Xin Schulte, Wibke Fan, Juan Lue, Hongqi Chen, Yibang Xiong, Huabao Chagnon, Frederic Bernhagen, Jürgen Lolis, Elias Mor, Gil Lesur, Olivier Bucala, Richard 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.1102941108 <jats:p> Macrophage migration inhibitory factor (MIF) is a pivotal regulator of the immune response. Neutralization or genetic deletion of MIF does not completely abrogate activation responses, however, and deletion of the MIF receptor, CD74, produces a more pronounced phenotype than MIF deficiency. We hypothesized that these observations may be explained by a second MIF-like ligand, and we considered a probable candidate to be the protein encoded by the homologous, <jats:italic>D</jats:italic> -dopachrome tautomerase (D-DT) gene. We show that recombinant D-DT protein binds CD74 with high affinity, leading to activation of ERK1/2 MAP kinase and downstream proinflammatory pathways. Circulating D-DT levels correlate with disease severity in sepsis or malignancy, and the specific immunoneutralization of D-DT protects mice from lethal endotoxemia by reducing the expression of downstream effector cytokines. These data indicate that D-DT is a MIF-like cytokine with an overlapping spectrum of activities that are important for our understanding of MIF-dependent physiology and pathology. </jats:p> The <i>D</i> -dopachrome tautomerase ( <i>DDT</i> ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) Proceedings of the National Academy of Sciences |
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| title |
The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) |
| title_unstemmed |
The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) |
| title_full |
The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) |
| title_fullStr |
The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) |
| title_full_unstemmed |
The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) |
| title_short |
The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) |
| title_sort |
the
<i>d</i>
-dopachrome tautomerase (
<i>ddt</i>
) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (mif) |
| topic |
Multidisciplinary |
| url |
http://dx.doi.org/10.1073/pnas.1102941108 |
| publishDate |
2011 |
| physical |
|
| description |
<jats:p>
Macrophage migration inhibitory factor (MIF) is a pivotal regulator of the immune response. Neutralization or genetic deletion of MIF does not completely abrogate activation responses, however, and deletion of the MIF receptor, CD74, produces a more pronounced phenotype than MIF deficiency. We hypothesized that these observations may be explained by a second MIF-like ligand, and we considered a probable candidate to be the protein encoded by the homologous,
<jats:italic>D</jats:italic>
-dopachrome tautomerase (D-DT) gene. We show that recombinant D-DT protein binds CD74 with high affinity, leading to activation of ERK1/2 MAP kinase and downstream proinflammatory pathways. Circulating D-DT levels correlate with disease severity in sepsis or malignancy, and the specific immunoneutralization of D-DT protects mice from lethal endotoxemia by reducing the expression of downstream effector cytokines. These data indicate that D-DT is a MIF-like cytokine with an overlapping spectrum of activities that are important for our understanding of MIF-dependent physiology and pathology.
</jats:p> |
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| author_facet | Merk, Melanie, Zierow, Swen, Leng, Lin, Das, Rituparna, Du, Xin, Schulte, Wibke, Fan, Juan, Lue, Hongqi, Chen, Yibang, Xiong, Huabao, Chagnon, Frederic, Bernhagen, Jürgen, Lolis, Elias, Mor, Gil, Lesur, Olivier, Bucala, Richard, Merk, Melanie, Zierow, Swen, Leng, Lin, Das, Rituparna, Du, Xin, Schulte, Wibke, Fan, Juan, Lue, Hongqi, Chen, Yibang, Xiong, Huabao, Chagnon, Frederic, Bernhagen, Jürgen, Lolis, Elias, Mor, Gil, Lesur, Olivier, Bucala, Richard |
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| description | <jats:p> Macrophage migration inhibitory factor (MIF) is a pivotal regulator of the immune response. Neutralization or genetic deletion of MIF does not completely abrogate activation responses, however, and deletion of the MIF receptor, CD74, produces a more pronounced phenotype than MIF deficiency. We hypothesized that these observations may be explained by a second MIF-like ligand, and we considered a probable candidate to be the protein encoded by the homologous, <jats:italic>D</jats:italic> -dopachrome tautomerase (D-DT) gene. We show that recombinant D-DT protein binds CD74 with high affinity, leading to activation of ERK1/2 MAP kinase and downstream proinflammatory pathways. Circulating D-DT levels correlate with disease severity in sepsis or malignancy, and the specific immunoneutralization of D-DT protects mice from lethal endotoxemia by reducing the expression of downstream effector cytokines. These data indicate that D-DT is a MIF-like cytokine with an overlapping spectrum of activities that are important for our understanding of MIF-dependent physiology and pathology. </jats:p> |
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| spelling | Merk, Melanie Zierow, Swen Leng, Lin Das, Rituparna Du, Xin Schulte, Wibke Fan, Juan Lue, Hongqi Chen, Yibang Xiong, Huabao Chagnon, Frederic Bernhagen, Jürgen Lolis, Elias Mor, Gil Lesur, Olivier Bucala, Richard 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.1102941108 <jats:p> Macrophage migration inhibitory factor (MIF) is a pivotal regulator of the immune response. Neutralization or genetic deletion of MIF does not completely abrogate activation responses, however, and deletion of the MIF receptor, CD74, produces a more pronounced phenotype than MIF deficiency. We hypothesized that these observations may be explained by a second MIF-like ligand, and we considered a probable candidate to be the protein encoded by the homologous, <jats:italic>D</jats:italic> -dopachrome tautomerase (D-DT) gene. We show that recombinant D-DT protein binds CD74 with high affinity, leading to activation of ERK1/2 MAP kinase and downstream proinflammatory pathways. Circulating D-DT levels correlate with disease severity in sepsis or malignancy, and the specific immunoneutralization of D-DT protects mice from lethal endotoxemia by reducing the expression of downstream effector cytokines. These data indicate that D-DT is a MIF-like cytokine with an overlapping spectrum of activities that are important for our understanding of MIF-dependent physiology and pathology. </jats:p> The <i>D</i> -dopachrome tautomerase ( <i>DDT</i> ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) Proceedings of the National Academy of Sciences |
| spellingShingle | Merk, Melanie, Zierow, Swen, Leng, Lin, Das, Rituparna, Du, Xin, Schulte, Wibke, Fan, Juan, Lue, Hongqi, Chen, Yibang, Xiong, Huabao, Chagnon, Frederic, Bernhagen, Jürgen, Lolis, Elias, Mor, Gil, Lesur, Olivier, Bucala, Richard, Proceedings of the National Academy of Sciences, The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF), Multidisciplinary |
| title | The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) |
| title_full | The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) |
| title_fullStr | The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) |
| title_full_unstemmed | The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) |
| title_short | The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) |
| title_sort | the <i>d</i> -dopachrome tautomerase ( <i>ddt</i> ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (mif) |
| title_unstemmed | The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF) |
| topic | Multidisciplinary |
| url | http://dx.doi.org/10.1073/pnas.1102941108 |