Evidence for involvement of TNFR1 and TIMPs in pathogenesis of post-kala-azar dermal leishmaniasis.
Semi-quantitative RT-PCR was exploited to analyse the intralesional cytokine gene expression in 14 post-kala-azar dermal leishmaniasis (PKDL) and 10 kala-azar (KA) patients. The data provided evidence for both inflammatory and non-inflammatory responses, as reflected by elevated tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 in PKDL lesions compared with normal skin tissue (n = 6). The ratio of TNF-alpha : IL-10 message was 2.66 in PKDL cases, substantially higher than in KA (1.18). Investigation of TNF-alpha receptors (TNFR1 and TNFR2) revealed a significant down-regulation of TNFR1 transcript in both PKDL and KA compared with control. In the presence of elevated levels of TNF-alpha transcript, interference with type 1 effector activity in PKDL may be due to minimal expression of the TNFR1 gene. Investigation of matrix metalloproteinases, known to be induced by TNF-alpha, and the tissue inhibitors of matrix metalloproteinases (TIMPs), provided evidence for the roles of TIMP-1 and TIMP-3 in the pathogenesis of PKDL.
Ansari
N A
NA
Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Dehli, India.
Katara
G K
GK
Ramesh
V
V
Salotra
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C088390:TIMP3 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D020780:Matrix Metalloproteinase 9