IL-6 regulates adipose deposition and homeostasis in lymphedema
Identifieur interne : 002A14 ( Main/Exploration ); précédent : 002A13; suivant : 002A15IL-6 regulates adipose deposition and homeostasis in lymphedema
Auteurs : Daniel A. Cuzzone [États-Unis] ; Evan S. Weitman [États-Unis] ; Nicholas J. Albano [États-Unis] ; Swapna Ghanta [États-Unis] ; Ira L. Savetsky [États-Unis] ; Jason C. Gardenier [États-Unis] ; Walter J. Joseph [États-Unis] ; Jeremy S. Torrisi [États-Unis] ; Jacqueline F. Bromberg [États-Unis] ; Waldemar L. Olszewski [Pologne] ; Stanley G. Rockson [États-Unis] ; Babak J. Mehrara [États-Unis]Source :
- American Journal of Physiology - Heart and Circulatory Physiology [ 0363-6135 ] ; 2014.
Descripteurs français
- KwdFr :
- Adiposité (physiologie), Animaux, Biopsie, Femelle, Homéostasie (physiologie), Humains, Interleukine-6 (déficit), Interleukine-6 (génétique), Interleukine-6 (physiologie), Lymphocytes T CD4+ (anatomopathologie), Lymphoedème (anatomopathologie), Lymphoedème (physiopathologie), Modèles animaux de maladie humaine, Souris, Souris de lignée C57BL, Souris knockout, Tissu adipeux (anatomopathologie), Tissu adipeux (physiopathologie), Tissu lymphoïde (anatomopathologie), Tissu lymphoïde (physiopathologie), Tissu lymphoïde (traumatismes), Études cas-témoins.
- MESH :
- anatomopathologie : Lymphocytes T CD4+, Lymphoedème, Tissu adipeux, Tissu lymphoïde.
- déficit : Interleukine-6.
- génétique : Interleukine-6.
- physiologie : Adiposité, Homéostasie, Interleukine-6.
- physiopathologie : Lymphoedème, Tissu adipeux, Tissu lymphoïde.
- traumatismes : Tissu lymphoïde.
- Animaux, Biopsie, Femelle, Humains, Modèles animaux de maladie humaine, Souris, Souris de lignée C57BL, Souris knockout, Études cas-témoins.
English descriptors
- KwdEn :
- Adipose Tissue (pathology), Adipose Tissue (physiopathology), Adiposity (physiology), Animals, Biopsy, CD4-Positive T-Lymphocytes (pathology), Case-Control Studies, Disease Models, Animal, Female, Homeostasis (physiology), Humans, Interleukin-6 (deficiency), Interleukin-6 (genetics), Interleukin-6 (physiology), Lymphedema (pathology), Lymphedema (physiopathology), Lymphoid Tissue (injuries), Lymphoid Tissue (pathology), Lymphoid Tissue (physiopathology), Mice, Mice, Inbred C57BL, Mice, Knockout.
- MESH :
- chemical , deficiency : Interleukin-6.
- chemical , genetics : Interleukin-6.
- injuries : Lymphoid Tissue.
- pathology : Adipose Tissue, CD4-Positive T-Lymphocytes, Lymphedema, Lymphoid Tissue.
- physiology : Adiposity, Homeostasis, Interleukin-6.
- physiopathology : Adipose Tissue, Lymphedema, Lymphoid Tissue.
- Animals, Biopsy, Case-Control Studies, Disease Models, Animal, Female, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout.
Abstract
Lymphedema (LE) is a morbid disease characterized by chronic limb swelling and adipose deposition. Although it is clear that lymphatic injury is necessary for this pathology, the mechanisms that underlie lymphedema remain unknown. IL-6 is a known regulator of adipose homeostasis in obesity and has been shown to be increased in primary and secondary models of lymphedema. Therefore, the purpose of this study was to determine the role of IL-6 in adipose deposition in lymphedema. The expression of IL-6 was analyzed in clinical tissue specimens and serum from patients with or without LE, as well as in two mouse models of lymphatic injury. In addition, we analyzed IL-6 expression/adipose deposition in mice deficient in CD4+ cells (CD4KO) or IL-6 expression (IL-6KO) or mice treated with a small molecule inhibitor of IL-6 or CD4 depleting antibodies to determine how IL-6 expression is regulated and the effect of changes in IL-6 expression on adipose deposition after lymphatic injury. Patients with LE and mice treated with lymphatic excision of the tail had significantly elevated tissue and serum expression of IL-6 and its downstream mediator. The expression of IL-6 was associated with adipose deposition and CD4+ inflammation and was markedly decreased in CD4KO mice. Loss of IL-6 function resulted in significantly increased adipose deposition after tail lymphatic injury. Our findings suggest that IL-6 is increased as a result of adipose deposition and CD4+ cell inflammation in lymphedema. In addition, our study suggests that IL-6 expression in lymphedema acts to limit adipose accumulation.
Url:
DOI: 10.1152/ajpheart.01019.2013
PubMed: 24633552
PubMed Central: 4024716
Affiliations:
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Cuzzone</name><affiliation wicri:level="2"><nlm:aff id="aff1">The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York</wicri:cityArea></affiliation></author><author><name sortKey="Weitman, Evan S" sort="Weitman, Evan S" uniqKey="Weitman E" first="Evan S." last="Weitman">Evan S. Weitman</name><affiliation wicri:level="2"><nlm:aff id="aff1">The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York</wicri:cityArea></affiliation></author><author><name sortKey="Albano, Nicholas J" sort="Albano, Nicholas J" uniqKey="Albano N" first="Nicholas J." last="Albano">Nicholas J. Albano</name><affiliation wicri:level="2"><nlm:aff id="aff1">The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York</wicri:cityArea></affiliation></author><author><name sortKey="Ghanta, Swapna" sort="Ghanta, Swapna" uniqKey="Ghanta S" first="Swapna" last="Ghanta">Swapna Ghanta</name><affiliation wicri:level="2"><nlm:aff id="aff1">The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York</wicri:cityArea></affiliation></author><author><name sortKey="Savetsky, Ira L" sort="Savetsky, Ira L" uniqKey="Savetsky I" first="Ira L." last="Savetsky">Ira L. Savetsky</name><affiliation wicri:level="2"><nlm:aff id="aff1">The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York</wicri:cityArea></affiliation></author><author><name sortKey="Gardenier, Jason C" sort="Gardenier, Jason C" uniqKey="Gardenier J" first="Jason C." last="Gardenier">Jason C. Gardenier</name><affiliation wicri:level="2"><nlm:aff id="aff1">The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York</wicri:cityArea></affiliation></author><author><name sortKey="Joseph, Walter J" sort="Joseph, Walter J" uniqKey="Joseph W" first="Walter J." last="Joseph">Walter J. Joseph</name><affiliation wicri:level="2"><nlm:aff id="aff1">The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York</wicri:cityArea></affiliation></author><author><name sortKey="Torrisi, Jeremy S" sort="Torrisi, Jeremy S" uniqKey="Torrisi J" first="Jeremy S." last="Torrisi">Jeremy S. Torrisi</name><affiliation wicri:level="2"><nlm:aff id="aff1">The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York</wicri:cityArea></affiliation></author><author><name sortKey="Bromberg, Jacqueline F" sort="Bromberg, Jacqueline F" uniqKey="Bromberg J" first="Jacqueline F." last="Bromberg">Jacqueline F. Bromberg</name><affiliation wicri:level="2"><nlm:aff id="aff2">The Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>The Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York</wicri:cityArea></affiliation></author><author><name sortKey="Olszewski, Waldemar L" sort="Olszewski, Waldemar L" uniqKey="Olszewski W" first="Waldemar L." last="Olszewski">Waldemar L. Olszewski</name><affiliation wicri:level="1"><nlm:aff id="aff3">The Department of Surgical Research and Transplantology, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland;</nlm:aff><country xml:lang="fr">Pologne</country><wicri:regionArea>The Department of Surgical Research and Transplantology, Medical Research Centre, Polish Academy of Sciences, Warsaw</wicri:regionArea><wicri:noRegion>Warsaw</wicri:noRegion></affiliation></author><author><name sortKey="Rockson, Stanley G" sort="Rockson, Stanley G" uniqKey="Rockson S" first="Stanley G." last="Rockson">Stanley G. Rockson</name><affiliation wicri:level="2"><nlm:aff id="aff4">The Department of Medicine, Division of Cardiology, Stanford University Medical Center, Stanford, California</nlm:aff><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>The Department of Medicine, Division of Cardiology, Stanford University Medical Center, Stanford</wicri:cityArea></affiliation></author><author><name sortKey="Mehrara, Babak J" sort="Mehrara, Babak J" uniqKey="Mehrara B" first="Babak J." last="Mehrara">Babak J. Mehrara</name><affiliation wicri:level="2"><nlm:aff id="aff1">The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York</wicri:cityArea></affiliation></author></analytic><series><title level="j">American Journal of Physiology - Heart and Circulatory Physiology</title><idno type="ISSN">0363-6135</idno><idno type="eISSN">1522-1539</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adipose Tissue (pathology)</term><term>Adipose Tissue (physiopathology)</term><term>Adiposity (physiology)</term><term>Animals</term><term>Biopsy</term><term>CD4-Positive T-Lymphocytes (pathology)</term><term>Case-Control Studies</term><term>Disease Models, Animal</term><term>Female</term><term>Homeostasis (physiology)</term><term>Humans</term><term>Interleukin-6 (deficiency)</term><term>Interleukin-6 (genetics)</term><term>Interleukin-6 (physiology)</term><term>Lymphedema (pathology)</term><term>Lymphedema (physiopathology)</term><term>Lymphoid Tissue (injuries)</term><term>Lymphoid Tissue (pathology)</term><term>Lymphoid Tissue (physiopathology)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adiposité (physiologie)</term><term>Animaux</term><term>Biopsie</term><term>Femelle</term><term>Homéostasie (physiologie)</term><term>Humains</term><term>Interleukine-6 (déficit)</term><term>Interleukine-6 (génétique)</term><term>Interleukine-6 (physiologie)</term><term>Lymphocytes T CD4+ (anatomopathologie)</term><term>Lymphoedème (anatomopathologie)</term><term>Lymphoedème (physiopathologie)</term><term>Modèles animaux de maladie humaine</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris knockout</term><term>Tissu adipeux (anatomopathologie)</term><term>Tissu adipeux (physiopathologie)</term><term>Tissu lymphoïde (anatomopathologie)</term><term>Tissu lymphoïde (physiopathologie)</term><term>Tissu lymphoïde (traumatismes)</term><term>Études cas-témoins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>Interleukin-6</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Interleukin-6</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Lymphocytes T CD4+</term><term>Lymphoedème</term><term>Tissu adipeux</term><term>Tissu lymphoïde</term></keywords><keywords scheme="MESH" qualifier="déficit" xml:lang="fr"><term>Interleukine-6</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Interleukine-6</term></keywords><keywords scheme="MESH" qualifier="injuries" xml:lang="en"><term>Lymphoid Tissue</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Adipose Tissue</term><term>CD4-Positive T-Lymphocytes</term><term>Lymphedema</term><term>Lymphoid Tissue</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Adiposité</term><term>Homéostasie</term><term>Interleukine-6</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Adiposity</term><term>Homeostasis</term><term>Interleukin-6</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Lymphoedème</term><term>Tissu adipeux</term><term>Tissu lymphoïde</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Adipose Tissue</term><term>Lymphedema</term><term>Lymphoid Tissue</term></keywords><keywords scheme="MESH" qualifier="traumatismes" xml:lang="fr"><term>Tissu lymphoïde</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Biopsy</term><term>Case-Control Studies</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Biopsie</term><term>Femelle</term><term>Humains</term><term>Modèles animaux de maladie humaine</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris knockout</term><term>Études cas-témoins</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Lymphedema (LE) is a morbid disease characterized by chronic limb swelling and adipose deposition. Although it is clear that lymphatic injury is necessary for this pathology, the mechanisms that underlie lymphedema remain unknown. IL-6 is a known regulator of adipose homeostasis in obesity and has been shown to be increased in primary and secondary models of lymphedema. Therefore, the purpose of this study was to determine the role of IL-6 in adipose deposition in lymphedema. The expression of IL-6 was analyzed in clinical tissue specimens and serum from patients with or without LE, as well as in two mouse models of lymphatic injury. In addition, we analyzed IL-6 expression/adipose deposition in mice deficient in CD4<sup>+</sup> cells (CD4KO) or IL-6 expression (IL-6KO) or mice treated with a small molecule inhibitor of IL-6 or CD4 depleting antibodies to determine how IL-6 expression is regulated and the effect of changes in IL-6 expression on adipose deposition after lymphatic injury. Patients with LE and mice treated with lymphatic excision of the tail had significantly elevated tissue and serum expression of IL-6 and its downstream mediator. The expression of IL-6 was associated with adipose deposition and CD4<sup>+</sup> inflammation and was markedly decreased in CD4KO mice. Loss of IL-6 function resulted in significantly increased adipose deposition after tail lymphatic injury. Our findings suggest that IL-6 is increased as a result of adipose deposition and CD4<sup>+</sup> cell inflammation in lymphedema. In addition, our study suggests that IL-6 expression in lymphedema acts to limit adipose accumulation.</p></div></front></TEI><affiliations><list><country><li>Pologne</li><li>États-Unis</li></country><region><li>Californie</li><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Cuzzone, Daniel A" sort="Cuzzone, Daniel A" uniqKey="Cuzzone D" first="Daniel A." last="Cuzzone">Daniel A. Cuzzone</name></region><name sortKey="Albano, Nicholas J" sort="Albano, Nicholas J" uniqKey="Albano N" first="Nicholas J." last="Albano">Nicholas J. Albano</name><name sortKey="Bromberg, Jacqueline F" sort="Bromberg, Jacqueline F" uniqKey="Bromberg J" first="Jacqueline F." last="Bromberg">Jacqueline F. Bromberg</name><name sortKey="Gardenier, Jason C" sort="Gardenier, Jason C" uniqKey="Gardenier J" first="Jason C." last="Gardenier">Jason C. Gardenier</name><name sortKey="Ghanta, Swapna" sort="Ghanta, Swapna" uniqKey="Ghanta S" first="Swapna" last="Ghanta">Swapna Ghanta</name><name sortKey="Joseph, Walter J" sort="Joseph, Walter J" uniqKey="Joseph W" first="Walter J." last="Joseph">Walter J. Joseph</name><name sortKey="Mehrara, Babak J" sort="Mehrara, Babak J" uniqKey="Mehrara B" first="Babak J." last="Mehrara">Babak J. Mehrara</name><name sortKey="Rockson, Stanley G" sort="Rockson, Stanley G" uniqKey="Rockson S" first="Stanley G." last="Rockson">Stanley G. Rockson</name><name sortKey="Savetsky, Ira L" sort="Savetsky, Ira L" uniqKey="Savetsky I" first="Ira L." last="Savetsky">Ira L. Savetsky</name><name sortKey="Torrisi, Jeremy S" sort="Torrisi, Jeremy S" uniqKey="Torrisi J" first="Jeremy S." last="Torrisi">Jeremy S. Torrisi</name><name sortKey="Weitman, Evan S" sort="Weitman, Evan S" uniqKey="Weitman E" first="Evan S." last="Weitman">Evan S. Weitman</name></country><country name="Pologne"><noRegion><name sortKey="Olszewski, Waldemar L" sort="Olszewski, Waldemar L" uniqKey="Olszewski W" first="Waldemar L." last="Olszewski">Waldemar L. Olszewski</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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