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

被引:13
作者
Anuradha, Rajamanickam [1 ]
George, Jovvian P. [1 ]
Pavankumar, Nathella [1 ]
Kumaraswami, Vasanthapuram [2 ]
Nutman, Thomas B. [3 ]
Babu, Subash [1 ,4 ]
机构
[1] Natl Inst Hlth, Int Ctr Excellence Res, Chennai, Tamil Nadu, India
[2] TB Res Ctr, Chennai, Tamil Nadu, India
[3] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA
[4] SAIC Frederick Inc, NCI Frederick, Frederick, MD USA
来源
PLOS NEGLECTED TROPICAL DISEASES | 2012年 / 6卷 / 06期
关键词
TISSUE INHIBITORS; BANCROFTIAN FILARIASIS; RHEUMATOID-ARTHRITIS; WUCHERERIA-BANCROFTI; CEREBROSPINAL-FLUID; GENE-EXPRESSION; FIBROSIS; TIMP-1; SERUM; MMP-9;
D O I
10.1371/journal.pntd.0001681
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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-beta). 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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页数:9
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