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Unexpected protective role for Toll-like receptor 3 in the arterial wall
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , |
| In: | Proceedings of the National Academy of Sciences, 108, 2011, 6, S. 2372-2377 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| author_facet |
Cole, Jennifer E. Navin, Tina J. Cross, Amanda J. Goddard, Michael E. Alexopoulou, Lena Mitra, Anuja T. Davies, Alun H. Flavell, Richard A. Feldmann, Marc Monaco, Claudia Cole, Jennifer E. Navin, Tina J. Cross, Amanda J. Goddard, Michael E. Alexopoulou, Lena Mitra, Anuja T. Davies, Alun H. Flavell, Richard A. Feldmann, Marc Monaco, Claudia |
|---|---|
| author |
Cole, Jennifer E. Navin, Tina J. Cross, Amanda J. Goddard, Michael E. Alexopoulou, Lena Mitra, Anuja T. Davies, Alun H. Flavell, Richard A. Feldmann, Marc Monaco, Claudia |
| spellingShingle |
Cole, Jennifer E. Navin, Tina J. Cross, Amanda J. Goddard, Michael E. Alexopoulou, Lena Mitra, Anuja T. Davies, Alun H. Flavell, Richard A. Feldmann, Marc Monaco, Claudia Proceedings of the National Academy of Sciences Unexpected protective role for Toll-like receptor 3 in the arterial wall Multidisciplinary |
| author_sort |
cole, jennifer e. |
| spelling |
Cole, Jennifer E. Navin, Tina J. Cross, Amanda J. Goddard, Michael E. Alexopoulou, Lena Mitra, Anuja T. Davies, Alun H. Flavell, Richard A. Feldmann, Marc Monaco, Claudia 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.1018515108 <jats:p> The critical role of Toll-like receptors (TLRs) in mammalian host defense has been extensively explored in recent years. The capacity of about 10 TLRs to recognize conserved patterns on many bacterial and viral pathogens is remarkable. With so few receptors, cross-reactivity with self-tissue components often occurs. Previous studies have frequently assigned detrimental roles to TLRs, in particular to TLR2 and TLR4, in immune and cardiovascular disease. Using human and murine systems, we have investigated the consequence of TLR3 signaling in vascular disease. We compared the responses of human atheroma-derived smooth muscle cells (AthSMC) and control aortic smooth muscle cells (AoSMC) to various TLR ligands. AthSMC exhibited a specific increase in TLR3 expression and TLR3-dependent functional responses. Intriguingly, exposure to dsRNA in vitro and in vivo induced increased expression of both pro- and anti-inflammatory genes in vascular cells and tissues. Therefore, we sought to assess the contribution of TLR3 signaling in vivo in mechanical and hypercholesterolemia-induced arterial injury. Surprisingly, neointima formation in a perivascular collar-induced injury model was reduced by the systemic administration of the dsRNA analog Poly(I:C) in a TLR3-dependent manner. Furthermore, genetic deletion of TLR3 dramatically enhanced the development of elastic lamina damage after collar-induced injury. Accordingly, deficiency of TLR3 accelerated the onset of atherosclerosis in hypercholesterolemic ApoE <jats:sup>−/−</jats:sup> mice. Collectively, our data describe a protective role for TLR signaling in the vessel wall. </jats:p> Unexpected protective role for Toll-like receptor 3 in the arterial wall Proceedings of the National Academy of Sciences |
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| title |
Unexpected protective role for Toll-like receptor 3 in the arterial wall |
| title_unstemmed |
Unexpected protective role for Toll-like receptor 3 in the arterial wall |
| title_full |
Unexpected protective role for Toll-like receptor 3 in the arterial wall |
| title_fullStr |
Unexpected protective role for Toll-like receptor 3 in the arterial wall |
| title_full_unstemmed |
Unexpected protective role for Toll-like receptor 3 in the arterial wall |
| title_short |
Unexpected protective role for Toll-like receptor 3 in the arterial wall |
| title_sort |
unexpected protective role for toll-like receptor 3 in the arterial wall |
| topic |
Multidisciplinary |
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http://dx.doi.org/10.1073/pnas.1018515108 |
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2011 |
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2372-2377 |
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<jats:p>
The critical role of Toll-like receptors (TLRs) in mammalian host defense has been extensively explored in recent years. The capacity of about 10 TLRs to recognize conserved patterns on many bacterial and viral pathogens is remarkable. With so few receptors, cross-reactivity with self-tissue components often occurs. Previous studies have frequently assigned detrimental roles to TLRs, in particular to TLR2 and TLR4, in immune and cardiovascular disease. Using human and murine systems, we have investigated the consequence of TLR3 signaling in vascular disease. We compared the responses of human atheroma-derived smooth muscle cells (AthSMC) and control aortic smooth muscle cells (AoSMC) to various TLR ligands. AthSMC exhibited a specific increase in TLR3 expression and TLR3-dependent functional responses. Intriguingly, exposure to dsRNA in vitro and in vivo induced increased expression of both pro- and anti-inflammatory genes in vascular cells and tissues. Therefore, we sought to assess the contribution of TLR3 signaling in vivo in mechanical and hypercholesterolemia-induced arterial injury. Surprisingly, neointima formation in a perivascular collar-induced injury model was reduced by the systemic administration of the dsRNA analog Poly(I:C) in a TLR3-dependent manner. Furthermore, genetic deletion of TLR3 dramatically enhanced the development of elastic lamina damage after collar-induced injury. Accordingly, deficiency of TLR3 accelerated the onset of atherosclerosis in hypercholesterolemic ApoE
<jats:sup>−/−</jats:sup>
mice. Collectively, our data describe a protective role for TLR signaling in the vessel wall.
</jats:p> |
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| author | Cole, Jennifer E., Navin, Tina J., Cross, Amanda J., Goddard, Michael E., Alexopoulou, Lena, Mitra, Anuja T., Davies, Alun H., Flavell, Richard A., Feldmann, Marc, Monaco, Claudia |
| author_facet | Cole, Jennifer E., Navin, Tina J., Cross, Amanda J., Goddard, Michael E., Alexopoulou, Lena, Mitra, Anuja T., Davies, Alun H., Flavell, Richard A., Feldmann, Marc, Monaco, Claudia, Cole, Jennifer E., Navin, Tina J., Cross, Amanda J., Goddard, Michael E., Alexopoulou, Lena, Mitra, Anuja T., Davies, Alun H., Flavell, Richard A., Feldmann, Marc, Monaco, Claudia |
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| description | <jats:p> The critical role of Toll-like receptors (TLRs) in mammalian host defense has been extensively explored in recent years. The capacity of about 10 TLRs to recognize conserved patterns on many bacterial and viral pathogens is remarkable. With so few receptors, cross-reactivity with self-tissue components often occurs. Previous studies have frequently assigned detrimental roles to TLRs, in particular to TLR2 and TLR4, in immune and cardiovascular disease. Using human and murine systems, we have investigated the consequence of TLR3 signaling in vascular disease. We compared the responses of human atheroma-derived smooth muscle cells (AthSMC) and control aortic smooth muscle cells (AoSMC) to various TLR ligands. AthSMC exhibited a specific increase in TLR3 expression and TLR3-dependent functional responses. Intriguingly, exposure to dsRNA in vitro and in vivo induced increased expression of both pro- and anti-inflammatory genes in vascular cells and tissues. Therefore, we sought to assess the contribution of TLR3 signaling in vivo in mechanical and hypercholesterolemia-induced arterial injury. Surprisingly, neointima formation in a perivascular collar-induced injury model was reduced by the systemic administration of the dsRNA analog Poly(I:C) in a TLR3-dependent manner. Furthermore, genetic deletion of TLR3 dramatically enhanced the development of elastic lamina damage after collar-induced injury. Accordingly, deficiency of TLR3 accelerated the onset of atherosclerosis in hypercholesterolemic ApoE <jats:sup>−/−</jats:sup> mice. Collectively, our data describe a protective role for TLR signaling in the vessel wall. </jats:p> |
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| institution | DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1 |
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| spelling | Cole, Jennifer E. Navin, Tina J. Cross, Amanda J. Goddard, Michael E. Alexopoulou, Lena Mitra, Anuja T. Davies, Alun H. Flavell, Richard A. Feldmann, Marc Monaco, Claudia 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.1018515108 <jats:p> The critical role of Toll-like receptors (TLRs) in mammalian host defense has been extensively explored in recent years. The capacity of about 10 TLRs to recognize conserved patterns on many bacterial and viral pathogens is remarkable. With so few receptors, cross-reactivity with self-tissue components often occurs. Previous studies have frequently assigned detrimental roles to TLRs, in particular to TLR2 and TLR4, in immune and cardiovascular disease. Using human and murine systems, we have investigated the consequence of TLR3 signaling in vascular disease. We compared the responses of human atheroma-derived smooth muscle cells (AthSMC) and control aortic smooth muscle cells (AoSMC) to various TLR ligands. AthSMC exhibited a specific increase in TLR3 expression and TLR3-dependent functional responses. Intriguingly, exposure to dsRNA in vitro and in vivo induced increased expression of both pro- and anti-inflammatory genes in vascular cells and tissues. Therefore, we sought to assess the contribution of TLR3 signaling in vivo in mechanical and hypercholesterolemia-induced arterial injury. Surprisingly, neointima formation in a perivascular collar-induced injury model was reduced by the systemic administration of the dsRNA analog Poly(I:C) in a TLR3-dependent manner. Furthermore, genetic deletion of TLR3 dramatically enhanced the development of elastic lamina damage after collar-induced injury. Accordingly, deficiency of TLR3 accelerated the onset of atherosclerosis in hypercholesterolemic ApoE <jats:sup>−/−</jats:sup> mice. Collectively, our data describe a protective role for TLR signaling in the vessel wall. </jats:p> Unexpected protective role for Toll-like receptor 3 in the arterial wall Proceedings of the National Academy of Sciences |
| spellingShingle | Cole, Jennifer E., Navin, Tina J., Cross, Amanda J., Goddard, Michael E., Alexopoulou, Lena, Mitra, Anuja T., Davies, Alun H., Flavell, Richard A., Feldmann, Marc, Monaco, Claudia, Proceedings of the National Academy of Sciences, Unexpected protective role for Toll-like receptor 3 in the arterial wall, Multidisciplinary |
| title | Unexpected protective role for Toll-like receptor 3 in the arterial wall |
| title_full | Unexpected protective role for Toll-like receptor 3 in the arterial wall |
| title_fullStr | Unexpected protective role for Toll-like receptor 3 in the arterial wall |
| title_full_unstemmed | Unexpected protective role for Toll-like receptor 3 in the arterial wall |
| title_short | Unexpected protective role for Toll-like receptor 3 in the arterial wall |
| title_sort | unexpected protective role for toll-like receptor 3 in the arterial wall |
| title_unstemmed | Unexpected protective role for Toll-like receptor 3 in the arterial wall |
| topic | Multidisciplinary |
| url | http://dx.doi.org/10.1073/pnas.1018515108 |