02979nas a2200457 4500000000100000008004100001260001300042653001000055653001800065653001100083653003000094653001100124653002500135653002400160653001700184653002700201653001200228653001500240653000900255653003000264653002500294653001600319653002500335653000900360653001600369100001200385700001200397700001400409700001200423700002100435700001500456700001800471700001200489700001200501700001400513245013400527300001200661490000700673520182700680022001402507 2010 d c2010 Mar10aAdult10aCell Movement10aFemale10aGene Expression Profiling10aHumans10aImmunohistochemistry10aIn Vitro Techniques10aInflammation10aInflammation Mediators10aleprosy10aLeukocytes10aMale10aMatrix Metalloproteinases10aMicroscopy, Confocal10aMiddle Aged10aMycobacterium leprae10aSkin10aYoung Adult1 aTeles R1 aTeles R1 aAmadeu TP1 aMoura D1 aMendonça-Lima L1 aFerreira H1 aSantos IM C F1 aNery JA1 aSarno E1 aSampaio E00aHigh matrix metalloproteinase production correlates with immune activation and leukocyte migration in leprosy reactional lesions. a1012-210 v783 a
Gelatinases A and B (matrix metalloproteinase 2 [MMP-2] and MMP-9, respectively) can induce basal membrane breakdown and leukocyte migration, but their role in leprosy skin inflammation remains unclear. In this study, we analyzed clinical specimens from leprosy patients taken from stable, untreated skin lesions and during reactional episodes (reversal reaction [RR] and erythema nodosum leprosum [ENL]). The participation of MMPs in disease was suggested by (i) increased MMP mRNA expression levels in skin biopsy specimens correlating with the expression of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), (ii) the detection of the MMP protein and enzymatic activity within the inflammatory infiltrate, (iii) increased MMP levels in patient sera, and (iv) the in vitro induction of MMP-9 by Mycobacterium leprae and/or TNF-alpha. It was observed that IFN-gamma, TNF-alpha, MMP-2, and MMP-9 mRNA levels were higher in tuberculoid than lepromatous lesions. In contrast, interleukin-10 and tissue inhibitor of MMP (TIMP-1) message were not differentially modulated. These data correlated with the detection of the MMP protein evidenced by immunohistochemistry and confocal microscopy. When RR and ENL lesions were analyzed, an increase in TNF-alpha, MMP-2, and MMP-9, but not TIMP-1, mRNA levels was observed together with stronger MMP activity (zymography/in situ zymography). Moreover, following in vitro stimulation of peripheral blood cells, M. leprae induced the expression of MMP-9 (mRNA and protein) in cultured cells. Overall, the present data demonstrate an enhanced MMP/TIMP-1 ratio in the inflammatory states of leprosy and point to potential mechanisms for tissue damage. These results pave the way toward the application of new therapeutic interventions for leprosy reactions.
a1098-5522