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

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 tissu...

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Autores principales: Anuradha, Rajamanickam, George, Jovvian P., Pavankumar, Nathella, Kumaraswami, Vasanthapuram, Nutman, Thomas B., Babu, Subash
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367978/
https://www.ncbi.nlm.nih.gov/pubmed/22679524
http://dx.doi.org/10.1371/journal.pntd.0001681
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author Anuradha, Rajamanickam
George, Jovvian P.
Pavankumar, Nathella
Kumaraswami, Vasanthapuram
Nutman, Thomas B.
Babu, Subash
author_facet Anuradha, Rajamanickam
George, Jovvian P.
Pavankumar, Nathella
Kumaraswami, Vasanthapuram
Nutman, Thomas B.
Babu, Subash
author_sort Anuradha, Rajamanickam
collection PubMed
description 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.
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spelling pubmed-33679782012-06-07 Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease Anuradha, Rajamanickam George, Jovvian P. Pavankumar, Nathella Kumaraswami, Vasanthapuram Nutman, Thomas B. Babu, Subash PLoS Negl Trop Dis Research Article 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. Public Library of Science 2012-06-05 /pmc/articles/PMC3367978/ /pubmed/22679524 http://dx.doi.org/10.1371/journal.pntd.0001681 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Anuradha, Rajamanickam
George, Jovvian P.
Pavankumar, Nathella
Kumaraswami, Vasanthapuram
Nutman, Thomas B.
Babu, Subash
Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease
title Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease
title_full Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease
title_fullStr Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease
title_full_unstemmed Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease
title_short Altered Circulating Levels of Matrix Metalloproteinases and Inhibitors Associated with Elevated Type 2 Cytokines in Lymphatic Filarial Disease
title_sort altered circulating levels of matrix metalloproteinases and inhibitors associated with elevated type 2 cytokines in lymphatic filarial disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367978/
https://www.ncbi.nlm.nih.gov/pubmed/22679524
http://dx.doi.org/10.1371/journal.pntd.0001681
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