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Interleukin-8 reduces post-surgical lymphedema formation by promoting lymphatic vessel regeneration.

Identifieur interne : 001A86 ( PubMed/Checkpoint ); précédent : 001A85; suivant : 001A87

Interleukin-8 reduces post-surgical lymphedema formation by promoting lymphatic vessel regeneration.

Auteurs : Inho Choi [États-Unis] ; Yong Suk Lee ; Hee Kyoung Chung ; Dongwon Choi ; Tatiana Ecoiffier ; Ha Neul Lee ; Kyu Eui Kim ; Sunju Lee ; Eun Kyung Park ; Yong Sun Maeng ; Nam Yun Kim ; Robert D. Ladner ; Nicos A. Petasis ; Chester J. Koh ; Lu Chen ; Heinz-Josef Lenz ; Young-Kwon Hong

Source :

RBID : pubmed:22945845

Descripteurs français

English descriptors

Abstract

Lymphedema is mainly caused by lymphatic obstruction and manifested as tissue swelling, often in the arms and legs. Lymphedema is one of the most common post-surgical complications in breast cancer patients and presents a painful and disfiguring chronic illness that has few treatment options. Here, we evaluated the therapeutic potential of interleukin (IL)-8 in lymphatic regeneration independent of its pro-inflammatory activity. We found that IL-8 promoted proliferation, tube formation, and migration of lymphatic endothelial cells (LECs) without activating the VEGF signaling. Additionally, IL-8 suppressed the major cell cycle inhibitor CDKN1C/p57(KIP2) by downregulating its positive regulator PROX1, which is known as the master regulator of LEC-differentiation. Animal-based studies such as matrigel plug and cornea micropocket assays demonstrated potent efficacy of IL-8 in activating lymphangiogenesis in vivo. Moreover, we have generated a novel transgenic mouse model (K14-hIL8) that expresses human IL-8 in the skin and then crossed with lymphatic-specific fluorescent (Prox1-GFP) mouse. The resulting double transgenic mice showed that a stable expression of IL-8 could promote embryonic lymphangiogenesis. Moreover, an immunodeficient IL-8-expressing mouse line that was established by crossing K14-hIL8 mice with athymic nude mice displayed an enhanced tumor-associated lymphangiogenesis. Finally, when experimental lymphedema was introduced, K14-hIL8 mice showed an improved amelioration of lymphedema with an increased lymphatic regeneration. Together, we report that IL-8 can activate lymphangiogenesis in vitro and in vivo with a therapeutic efficacy in post-surgical lymphedema.

DOI: 10.1007/s10456-012-9297-6
PubMed: 22945845


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<term>Animals</term>
<term>Cell Proliferation (drug effects)</term>
<term>Cells, Cultured</term>
<term>Cyclin-Dependent Kinase Inhibitor p57 (metabolism)</term>
<term>Down-Regulation (drug effects)</term>
<term>Embryonic Development (drug effects)</term>
<term>Endothelial Cells (drug effects)</term>
<term>Endothelial Cells (metabolism)</term>
<term>Homeodomain Proteins (metabolism)</term>
<term>Humans</term>
<term>Interleukin-8 (metabolism)</term>
<term>Interleukin-8 (pharmacology)</term>
<term>Interleukin-8 (therapeutic use)</term>
<term>Lymphangiogenesis (drug effects)</term>
<term>Lymphatic Vessels (drug effects)</term>
<term>Lymphatic Vessels (pathology)</term>
<term>Lymphatic Vessels (physiopathology)</term>
<term>Lymphedema (drug therapy)</term>
<term>Lymphedema (etiology)</term>
<term>Lymphedema (pathology)</term>
<term>Lymphedema (physiopathology)</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Neovascularization, Physiologic (drug effects)</term>
<term>Postoperative Complications (drug therapy)</term>
<term>Postoperative Complications (etiology)</term>
<term>Postoperative Complications (pathology)</term>
<term>Postoperative Complications (physiopathology)</term>
<term>Receptors, Interleukin-8 (metabolism)</term>
<term>Receptors, Interleukin-8A (metabolism)</term>
<term>Receptors, Interleukin-8B (metabolism)</term>
<term>Regeneration (drug effects)</term>
<term>Tretinoin (pharmacology)</term>
<term>Tumor Microenvironment (drug effects)</term>
<term>Tumor Necrosis Factor-alpha (pharmacology)</term>
<term>Tumor Suppressor Proteins (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Animaux</term>
<term>Cellules cultivées</term>
<term>Cellules endothéliales ()</term>
<term>Cellules endothéliales (métabolisme)</term>
<term>Complications postopératoires (anatomopathologie)</term>
<term>Complications postopératoires (physiopathologie)</term>
<term>Complications postopératoires (traitement médicamenteux)</term>
<term>Complications postopératoires (étiologie)</term>
<term>Développement embryonnaire ()</term>
<term>Facteur de nécrose tumorale alpha (pharmacologie)</term>
<term>Humains</term>
<term>Inhibiteur p57 de kinase cycline-dépendante (métabolisme)</term>
<term>Interleukine-8 (métabolisme)</term>
<term>Interleukine-8 (pharmacologie)</term>
<term>Interleukine-8 (usage thérapeutique)</term>
<term>Lymphangiogenèse ()</term>
<term>Lymphoedème (anatomopathologie)</term>
<term>Lymphoedème (physiopathologie)</term>
<term>Lymphoedème (traitement médicamenteux)</term>
<term>Lymphoedème (étiologie)</term>
<term>Microenvironnement tumoral ()</term>
<term>Néovascularisation physiologique ()</term>
<term>Prolifération cellulaire ()</term>
<term>Protéines suppresseurs de tumeurs (métabolisme)</term>
<term>Protéines à homéodomaine (métabolisme)</term>
<term>Récepteurs à l'interleukine-8 (métabolisme)</term>
<term>Récepteurs à l'interleukine-8A (métabolisme)</term>
<term>Récepteurs à l'interleukine-8B (métabolisme)</term>
<term>Régulation négative ()</term>
<term>Régénération ()</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Trétinoïne (pharmacologie)</term>
<term>Vaisseaux lymphatiques ()</term>
<term>Vaisseaux lymphatiques (anatomopathologie)</term>
<term>Vaisseaux lymphatiques (physiopathologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Cyclin-Dependent Kinase Inhibitor p57</term>
<term>Homeodomain Proteins</term>
<term>Interleukin-8</term>
<term>Receptors, Interleukin-8</term>
<term>Receptors, Interleukin-8A</term>
<term>Receptors, Interleukin-8B</term>
<term>Tumor Suppressor Proteins</term>
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<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr">
<term>Complications postopératoires</term>
<term>Lymphoedème</term>
<term>Vaisseaux lymphatiques</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Cell Proliferation</term>
<term>Down-Regulation</term>
<term>Embryonic Development</term>
<term>Endothelial Cells</term>
<term>Lymphangiogenesis</term>
<term>Lymphatic Vessels</term>
<term>Neovascularization, Physiologic</term>
<term>Regeneration</term>
<term>Tumor Microenvironment</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en">
<term>Lymphedema</term>
<term>Postoperative Complications</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en">
<term>Lymphedema</term>
<term>Postoperative Complications</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Endothelial Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Cellules endothéliales</term>
<term>Inhibiteur p57 de kinase cycline-dépendante</term>
<term>Interleukine-8</term>
<term>Protéines suppresseurs de tumeurs</term>
<term>Protéines à homéodomaine</term>
<term>Récepteurs à l'interleukine-8</term>
<term>Récepteurs à l'interleukine-8A</term>
<term>Récepteurs à l'interleukine-8B</term>
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<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Lymphatic Vessels</term>
<term>Lymphedema</term>
<term>Postoperative Complications</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr">
<term>Facteur de nécrose tumorale alpha</term>
<term>Interleukine-8</term>
<term>Trétinoïne</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en">
<term>Interleukin-8</term>
<term>Tretinoin</term>
<term>Tumor Necrosis Factor-alpha</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr">
<term>Complications postopératoires</term>
<term>Lymphoedème</term>
<term>Vaisseaux lymphatiques</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en">
<term>Lymphatic Vessels</term>
<term>Lymphedema</term>
<term>Postoperative Complications</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en">
<term>Interleukin-8</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr">
<term>Complications postopératoires</term>
<term>Lymphoedème</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr">
<term>Interleukine-8</term>
</keywords>
<keywords scheme="MESH" qualifier="étiologie" xml:lang="fr">
<term>Complications postopératoires</term>
<term>Lymphoedème</term>
</keywords>
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<term>Animals</term>
<term>Cells, Cultured</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
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<term>Cellules cultivées</term>
<term>Cellules endothéliales</term>
<term>Développement embryonnaire</term>
<term>Humains</term>
<term>Lymphangiogenèse</term>
<term>Microenvironnement tumoral</term>
<term>Néovascularisation physiologique</term>
<term>Prolifération cellulaire</term>
<term>Régulation négative</term>
<term>Régénération</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Vaisseaux lymphatiques</term>
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<front>
<div type="abstract" xml:lang="en">Lymphedema is mainly caused by lymphatic obstruction and manifested as tissue swelling, often in the arms and legs. Lymphedema is one of the most common post-surgical complications in breast cancer patients and presents a painful and disfiguring chronic illness that has few treatment options. Here, we evaluated the therapeutic potential of interleukin (IL)-8 in lymphatic regeneration independent of its pro-inflammatory activity. We found that IL-8 promoted proliferation, tube formation, and migration of lymphatic endothelial cells (LECs) without activating the VEGF signaling. Additionally, IL-8 suppressed the major cell cycle inhibitor CDKN1C/p57(KIP2) by downregulating its positive regulator PROX1, which is known as the master regulator of LEC-differentiation. Animal-based studies such as matrigel plug and cornea micropocket assays demonstrated potent efficacy of IL-8 in activating lymphangiogenesis in vivo. Moreover, we have generated a novel transgenic mouse model (K14-hIL8) that expresses human IL-8 in the skin and then crossed with lymphatic-specific fluorescent (Prox1-GFP) mouse. The resulting double transgenic mice showed that a stable expression of IL-8 could promote embryonic lymphangiogenesis. Moreover, an immunodeficient IL-8-expressing mouse line that was established by crossing K14-hIL8 mice with athymic nude mice displayed an enhanced tumor-associated lymphangiogenesis. Finally, when experimental lymphedema was introduced, K14-hIL8 mice showed an improved amelioration of lymphedema with an increased lymphatic regeneration. Together, we report that IL-8 can activate lymphangiogenesis in vitro and in vivo with a therapeutic efficacy in post-surgical lymphedema.</div>
</front>
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<DateCreated>
<Year>2012</Year>
<Month>12</Month>
<Day>20</Day>
</DateCreated>
<DateCompleted>
<Year>2013</Year>
<Month>05</Month>
<Day>30</Day>
</DateCompleted>
<DateRevised>
<Year>2017</Year>
<Month>07</Month>
<Day>26</Day>
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<JournalIssue CitedMedium="Internet">
<Volume>16</Volume>
<Issue>1</Issue>
<PubDate>
<Year>2013</Year>
<Month>Jan</Month>
</PubDate>
</JournalIssue>
<Title>Angiogenesis</Title>
<ISOAbbreviation>Angiogenesis</ISOAbbreviation>
</Journal>
<ArticleTitle>Interleukin-8 reduces post-surgical lymphedema formation by promoting lymphatic vessel regeneration.</ArticleTitle>
<Pagination>
<MedlinePgn>29-44</MedlinePgn>
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<ELocationID EIdType="doi" ValidYN="Y">10.1007/s10456-012-9297-6</ELocationID>
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<AbstractText>Lymphedema is mainly caused by lymphatic obstruction and manifested as tissue swelling, often in the arms and legs. Lymphedema is one of the most common post-surgical complications in breast cancer patients and presents a painful and disfiguring chronic illness that has few treatment options. Here, we evaluated the therapeutic potential of interleukin (IL)-8 in lymphatic regeneration independent of its pro-inflammatory activity. We found that IL-8 promoted proliferation, tube formation, and migration of lymphatic endothelial cells (LECs) without activating the VEGF signaling. Additionally, IL-8 suppressed the major cell cycle inhibitor CDKN1C/p57(KIP2) by downregulating its positive regulator PROX1, which is known as the master regulator of LEC-differentiation. Animal-based studies such as matrigel plug and cornea micropocket assays demonstrated potent efficacy of IL-8 in activating lymphangiogenesis in vivo. Moreover, we have generated a novel transgenic mouse model (K14-hIL8) that expresses human IL-8 in the skin and then crossed with lymphatic-specific fluorescent (Prox1-GFP) mouse. The resulting double transgenic mice showed that a stable expression of IL-8 could promote embryonic lymphangiogenesis. Moreover, an immunodeficient IL-8-expressing mouse line that was established by crossing K14-hIL8 mice with athymic nude mice displayed an enhanced tumor-associated lymphangiogenesis. Finally, when experimental lymphedema was introduced, K14-hIL8 mice showed an improved amelioration of lymphedema with an increased lymphatic regeneration. Together, we report that IL-8 can activate lymphangiogenesis in vitro and in vivo with a therapeutic efficacy in post-surgical lymphedema.</AbstractText>
</Abstract>
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<LastName>Lee</LastName>
<ForeName>Yong Suk</ForeName>
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<LastName>Chung</LastName>
<ForeName>Hee Kyoung</ForeName>
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<LastName>Choi</LastName>
<ForeName>Dongwon</ForeName>
<Initials>D</Initials>
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<LastName>Ecoiffier</LastName>
<ForeName>Tatiana</ForeName>
<Initials>T</Initials>
</Author>
<Author ValidYN="Y">
<LastName>Lee</LastName>
<ForeName>Ha Neul</ForeName>
<Initials>HN</Initials>
</Author>
<Author ValidYN="Y">
<LastName>Kim</LastName>
<ForeName>Kyu Eui</ForeName>
<Initials>KE</Initials>
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<ForeName>Yong Sun</ForeName>
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<ForeName>Nam Yun</ForeName>
<Initials>NY</Initials>
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   |flux=    PubMed
   |étape=   Checkpoint
   |type=    RBID
   |clé=     pubmed:22945845
   |texte=   Interleukin-8 reduces post-surgical lymphedema formation by promoting lymphatic vessel regeneration.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/RBID.i   -Sk "pubmed:22945845" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd   \
       | NlmPubMed2Wicri -a LymphedemaV1 

Wicri

This area was generated with Dilib version V0.6.31.
Data generation: Sat Nov 4 17:40:35 2017. Site generation: Tue Feb 13 16:42:16 2024