LymphedemaV1, Main, Exploration, bibRecord, 004520

Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease

Identifieur interne : 004520 ( Main/Exploration ); précédent : 004519; suivant : 004521

Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease

Auteurs : Rajamanickam Anuradha [Inde] ; Jovvian P. George [Inde] ; Nathella Pavankumar [Inde] ; Vasanthapuram Kumaraswami [Inde] ; Thomas B. Nutman [États-Unis] ; Subash Babu [Inde, États-Unis]

Source :

PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2012.

RBID : PMC:3367978

Descripteurs français

KwdFr :
- Adolescent, Adulte, Adulte d'âge moyen, Animaux, Cytokines (sang), Femelle, Filariose lymphatique (anatomopathologie), Humains, Inhibiteur tissulaire des métalloprotéinases (sang), Jeune adulte, Matrix metalloproteinases (sang), Mâle, Plasma sanguin (), Sujet âgé.
MESH :
- anatomopathologie : Filariose lymphatique.
- sang : Cytokines, Inhibiteur tissulaire des métalloprotéinases, Matrix metalloproteinases.
- Adolescent, Adulte, Adulte d'âge moyen, Animaux, Femelle, Humains, Jeune adulte, Mâle, Plasma sanguin, Sujet âgé.

English descriptors

KwdEn :
- Adolescent, Adult, Aged, Animals, Cytokines (blood), Elephantiasis, Filarial (pathology), Female, Humans, Male, Matrix Metalloproteinases (blood), Middle Aged, Plasma (chemistry), Tissue Inhibitor of Metalloproteinases (blood), Young Adult.
MESH :
- chemical , blood : Cytokines, Matrix Metalloproteinases, Tissue Inhibitor of Metalloproteinases.
- chemistry : Plasma.
- pathology : Elephantiasis, Filarial.
- Adolescent, Adult, Aged, Animals, Female, Humans, Male, Middle Aged, Young Adult.

Abstract

Background

Infection with Wuchereria bancrofti can cause severe disease characterized by subcutaneous fibrosis and extracellular matrix remodeling. Matrix metalloproteinases (MMPs) are a family of enzymes governing extracellular remodeling by regulating cellular homeostasis, inflammation, and tissue reorganization, while tissue-inhibitors of metalloproteinases (TIMPs) are endogenous regulators of MMPs. Homeostatic as well as inflammation-induced balance between MMPs and TIMPs is considered critical in mediating tissue pathology.

Methods

To elucidate the role of MMPs and TIMPs in filarial pathology, we compared the plasma levels of a panel of MMPs, TIMPs, other pro-fibrotic factors, and cytokines in individuals with chronic filarial pathology with (CP Ag+) or without (CP Ag−) active infection to those with clinically asymptomatic infections (INF) and in those without infection (endemic normal [EN]). Markers of pathogenesis were delineated based on comparisons between the two actively infected groups (CP Ag+ compared to INF) and those without active infection (CP Ag− compared to EN).

Results and Conclusion

Our data reveal that an increase in circulating levels of MMPs and TIMPs is characteristic of the filarial disease process per se and not of active infection; however, filarial disease with active infection is specifically associated with increased ratios of MMP1/TIMP4 and MMP8/TIMP4 as well as with pro-fibrotic cytokines (IL-5, IL-13 and TGF-β). Our data therefore suggest that while filarial lymphatic disease is characterized by a non-specific increase in plasma MMPs and TIMPs, the balance between MMPs and TIMPs is an important factor in regulating tissue pathology during active infection.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367978

DOI: 10.1371/journal.pntd.0001681
PubMed: 22679524
PubMed Central: 3367978

Affiliations:

Le document en format XML

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<term>Elephantiasis, Filarial (pathology)</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Matrix Metalloproteinases (blood)</term>
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<term>Femelle</term>
<term>Filariose lymphatique (anatomopathologie)</term>
<term>Humains</term>
<term>Inhibiteur tissulaire des métalloprotéinases (sang)</term>
<term>Jeune adulte</term>
<term>Matrix metalloproteinases (sang)</term>
<term>Mâle</term>
<term>Plasma sanguin ()</term>
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<term>Matrix Metalloproteinases</term>
<term>Tissue Inhibitor of Metalloproteinases</term>
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<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Filariose lymphatique</term>
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<keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Plasma</term>
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<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Elephantiasis, Filarial</term>
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<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Cytokines</term>
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<term>Matrix metalloproteinases</term>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Infection with <italic>Wuchereria bancrofti</italic>
 can cause severe disease characterized by subcutaneous fibrosis and extracellular matrix remodeling. Matrix metalloproteinases (MMPs) are a family of enzymes governing extracellular remodeling by regulating cellular homeostasis, inflammation, and tissue reorganization, while tissue-inhibitors of metalloproteinases (TIMPs) are endogenous regulators of MMPs. Homeostatic as well as inflammation-induced balance between MMPs and TIMPs is considered critical in mediating tissue pathology.</p>
</sec>
<sec><title>Methods</title>
<p>To elucidate the role of MMPs and TIMPs in filarial pathology, we compared the plasma levels of a panel of MMPs, TIMPs, other pro-fibrotic factors, and cytokines in individuals with chronic filarial pathology with (CP Ag+) or without (CP Ag−) active infection to those with clinically asymptomatic infections (INF) and in those without infection (endemic normal [EN]). Markers of pathogenesis were delineated based on comparisons between the two actively infected groups (CP Ag+ compared to INF) and those without active infection (CP Ag− compared to EN).</p>
</sec>
<sec><title>Results and Conclusion</title>
<p>Our data reveal that an increase in circulating levels of MMPs and TIMPs is characteristic of the filarial disease process <italic>per se</italic>
 and not of active infection; however, filarial disease with active infection is specifically associated with increased ratios of MMP1/TIMP4 and MMP8/TIMP4 as well as with pro-fibrotic cytokines (IL-5, IL-13 and TGF-β). Our data therefore suggest that while filarial lymphatic disease is characterized by a non-specific increase in plasma MMPs and TIMPs, the balance between MMPs and TIMPs is an important factor in regulating tissue pathology during active infection.</p>
</sec>
</div>
</front>
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Serveur d'exploration sur le lymphœdème

Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease

Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease

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