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Role of the Phosphatidylinositol 3-Kinase and Mitogen-Activated Protein Kinase Pathways in the Secretion of Tumor Necrosis Factor-α and Interleukin-10 by the PPD Antigen of Mycobacterium tuberculosis

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Abstract

Here we investigated the role of the phosphatidylinositol 3-kinase (PI 3-K) and mitogen-activated protein kinase (MAPK) pathways in the secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-10 in human primary monocytes after stimulation with the PPD antigen of Mycobacterium tuberculosis. MAPK [extracellular signal-regulated kinase (ERK) 1/2 and p38] and Akt are rapidly phosphorylated in human monocytes stimulated with PPD. We found that the PI 3-K-Akt pathway stimulated by PPD is essential for both IL-10 and TNF-α production, although the inhibition of IL-10 production was more pronounced. The analysis of cytokine production using specific inhibitors of the MAPK pathway revealed that both p38 and ERK activation are essential for PPD-induced TNF-α production, whereas p38, but not ERK, activation is essential for IL-10 secretion. The inhibition of PI 3-K did not significantly activate p38 MAPK or ERK 1/2 in PPD-stimulated human monocytes. Further, the Src inhibitor PP2 inhibited the release of TNF-α but enhanced IL-10 release, suggesting the differential regulation of Src kinase in upstream signaling. Collectively, these data suggest that the PI 3-K and MAPK pathways play a central role in the regulation of both pro- and anti-inflammatory cytokines by the PPD antigen of M. tuberculosis.

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Authors and Affiliations

  1. Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, South Korea

    Saet-Byel Jung, Chang-Hwa Song, Chul-Su Yang, Su-Young Kim, Kil-Soo Lee, A-Rum Shin, Hwa-Jung Kim, Jeong-Kyu Park & Eun-Kyeong Jo

  2. Department of Microbiology, College of Medicine, Konyang University, Nonsan, Chungnam, South Korea

    Ji-Sook Lee & Tae-Hyun Paik

  3. Department of Preventive Medicine, College of Medicine, Chungnam National University, Daejeon, South Korea

    Hae Sung Nam

  4. Department of Microbiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jungku, Daejeon, 301-747, South Korea

    Eun-Kyeong Jo

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  1. Saet-Byel Jung
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Correspondence to Eun-Kyeong Jo.

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Jung, SB., Song, CH., Yang, CS. et al. Role of the Phosphatidylinositol 3-Kinase and Mitogen-Activated Protein Kinase Pathways in the Secretion of Tumor Necrosis Factor-α and Interleukin-10 by the PPD Antigen of Mycobacterium tuberculosis. J Clin Immunol 25, 482–490 (2005). https://doi.org/10.1007/s10875-005-5431-1

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  • DOI: https://doi.org/10.1007/s10875-005-5431-1

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