Details:

Alternative Title:
PLoS Negl Trop Dis
Personal Author:
Anuradha, Rajamanickam ; George, Jovvian P. ; Pavankumar, Nathella ; Kumaraswami, Vasanthapuram ; Nutman, Thomas B. ; ... More +
Anuradha, Rajamanickam ; George, Jovvian P. ; Pavankumar, Nathella ; Kumaraswami, Vasanthapuram ; Nutman, Thomas B. ; Babu, Subash Less -
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.


Subject:
[+]
Adolescent
Adult
Aged
Animals
Biology
Cytokines
Elephantiasis, Filarial
Female
Humans
Male
Matrix Metalloproteinases
Medicine
Middle Aged
Plasma
Research Article
Tissue Inhibitor Of Metalloproteinases
Young Adult

Source:
PLoS Negl Trop Dis. 2012; 6(6).
Document Type:
Journal Article
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:47f69ee3430a635b60ee234a8d88be4fb01978adaf25fdfd7c65cfb530857fc1
File Type:

Supporting Files

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