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KMID : 0921620070370010011
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Journal of Bacteriology and Virology
2007 Volume.37 No. 1 p.11 ~ p.21
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Differential Roles of Toll-like Receptor (TLR) 2 and 4 between PPD- and 38-kDa-induced Proinflammatory Cytokine Productions in Human Monocytes
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Jung Saet-Byel
Lee Ji-Sook
Yang Chul-Su
Song Chang-Hwa
Lee Kil-Soo
Kim Hwa-Jung
Park Jung-Kyu
Paik Tae-Hyun
Jo Eun-Kyung
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Abstract
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In this study, we investigated the role of toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) pathways involved in the tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 expression after stimulation with purified protein derivatives (PPD) or native 38-kDa protein antigen (Ag) of Mycobacterium tuberculosis H37Rv in human primary monocytes. Both PPD and 38-kDa Ag significantly induced TNF-alpha and IL-6 in human primary monocytes. MAPK [extracellular signal-regulated kinase (ERK) 1/2 and p38] are rapidly phosphorylated in human monocytes stimulated with the PPD or 38-kDa Ag. Both p38 and ERK 1/2 activation are essential for PPD- or 38-kDa-induced TNF-alpha and IL-6 production. The inhibition of TLR2 and TLR4 by specific antibodies significantly abrogated the 38-kDa-induced secretion of TNF-alpha and IL-6, whereas blockade of TLR2, but not TLR4, was responsible for the PPD-induced TNF-alpha and IL-6 production in human monocytes. Collectively, these data suggest that the PPD and 38-kDa Ag differentially interact with TLR2 and TLR4, which in turn mediate an essential role for the early inflammatory immune responses during human tuberculosis.
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KEYWORD
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PPD antigen, 38-kDa antigen, Monocyte, TNF-alpha, IL-6, MAPK, Mycobacterium tuberculosis
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