RGD Reference Report - Therapeutic failure in American cutaneous leishmaniasis is associated with gelatinase activity and cytokine expression. - Rat Genome Database

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Therapeutic failure in American cutaneous leishmaniasis is associated with gelatinase activity and cytokine expression.

Authors: Maretti-Mira, AC  De Oliveira-Neto, MP  Da-Cruz, AM  De Oliveira, MP  Craft, N  Pirmez, C 
Citation: Maretti-Mira AC, etal., Clin Exp Immunol. 2011 Feb;163(2):207-14. doi: 10.1111/j.1365-2249.2010.04285.x. Epub 2010 Nov 22.
RGD ID: 8657030
Pubmed: PMID:21091666   (View Abstract at PubMed)
PMCID: PMC3043311   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1365-2249.2010.04285.x   (Journal Full-text)

Cutaneous lesions caused by Leishmania braziliensis infection occasionally heal spontaneously, but with antimonials therapy heal rapidly in approximately 3 weeks. However, about 15% of the cases require several courses of therapy. Matrix metalloproteinase-2 (MMP-2) and MMP-9 are gelatinases that have been implicated in other chronic cutaneous diseases and skin re-epithelialization. These enzymes are controlled by their natural inhibitors [tissue inhibitors of metalloproteinase (TIMPs)] and by some cytokines. Uncontrolled gelatinase activity may result in intense tissue degradation and, consequently, poorly healing wounds. The present study correlates gelatinase activity to therapeutic failure of cutaneous leishmaniasis (CL) lesions. Our results demonstrate an association between gelatinase activity and increased numbers of cells making interferon (IFN)-gamma, interleukin (IL)-10 and transforming growth factor (TGF)-beta in lesions from poor responders. Conversely, high levels of MMP-2 mRNA and enhanced MMP-2 : TIMP-2 ratios were associated with a satisfactory response to antimonials treatment. Additionally, high gelatinolytic activity was found in the wound beds, necrotic areas in the dermis and within some granulomatous infiltrates. These results indicate the importance of gelatinase activity in the skin lesions caused by CL. Thus, we hypothesize that the immune response profile may be responsible for the gelatinase activity pattern and may ultimately influence the persistence or cure of CL lesions.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cutaneous leishmaniasis treatmentIEP 8657030 RGD 
cutaneous leishmaniasis treatmentISOMMP2 (Homo sapiens)8657030; 8657030 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp2  (matrix metallopeptidase 2)

Genes (Mus musculus)
Mmp2  (matrix metallopeptidase 2)

Genes (Homo sapiens)
MMP2  (matrix metallopeptidase 2)


Additional Information