Matrix metalloproteinase 9 production by monocytes is enhanced by TNF and participates in the pathology of human cutaneous Leishmaniasis.

Abstract

INTRODUCTION:

Cutaneous leishmaniasis (CL) due to L.braziliensis infection is characterized by a strong inflammatory response with high levels of TNF and ulcer development. Less attention has been given to the role of mononuclear phagocytes to this process. Monocytes constitute a heterogeneous population subdivided into classical, intermediate and non-classical, and are known to migrate to inflammatory sites and secrete inflammatory mediators. TNF participates in the induction of matrix metalloproteinases (MMPs). MMP-9 is an enzyme that degrades basal membrane and its activity is controlled by the tissue inhibitor of metalloproteinase.

METHODS:

Mononuclear cells were obtained from ex-vivo labeling sub-populations of monocytes and MMP-9, and the frequency was determined by flow cytometry. Culture was performed during 72 hours, stimulating the cells with SLA, levels of MMP-9 and TIMP-1 in the supernatants were determined by ELISA.

RESULTS:

We observed that cells from CL lesions secrete high amounts of MMP-9 when compared to healthy subjects. Although MMP-9 was produced by monocytes, non-classical ones were the main source of this enzyme. We also observed that TNF produced in high level during CL contributes to MMP-9 production.

CONCLUSIONS:

These observations emphasize the role of monocytes, TNF and MMP-9 in the pathogenesis of L. braziliensis infection.

• Authors: Taís M Campos, Sara T Passos, Fernanda O Novais, Daniel P Beiting, Rúbia S Costa, Adriano Queiroz, David Mosser, Phillip Scott, Edgar M Carvalho, Lucas P Carvalho
• Journal: PLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 8 Issue 11 Pg. e3282 ( 2014) ISSN: 1935-2735 [Electronic] United States
• PMID: 25393535 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Matrix Metalloproteinase Inhibitors
• TIMP1 protein, human
• TNF protein, human
• Tissue Inhibitor of Metalloproteinase-1
• Tumor Necrosis Factor-alpha
• Matrix Metalloproteinase 9

Topics

• Gene Expression Profiling
• Gene Expression Regulation, Enzymologic
• Humans
• Leishmaniasis, Cutaneous (enzymology, metabolism, pathology)
• Leukocytes, Mononuclear (enzymology)
• Matrix Metalloproteinase 9 (metabolism)
• Matrix Metalloproteinase Inhibitors (metabolism)
• Monocytes (enzymology)
• Oligonucleotide Array Sequence Analysis
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation