Journal of Clinical Immunology

, Volume 25, Issue 5, pp 482–490 | Cite as

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

  • Saet-Byel Jung
  • Chang-Hwa Song
  • Chul-Su Yang
  • Su-Young Kim
  • Kil-Soo Lee
  • A-Rum Shin
  • Ji-Sook Lee
  • Hae Sung Nam
  • Hwa-Jung Kim
  • Jeong-Kyu Park
  • Tae-Hyun Paik
  • Eun-Kyeong Jo


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.


PPD antigen MAPK PI 3-K tumor necrosis factor-α interleukin-10 


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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Saet-Byel Jung
    • 1
  • Chang-Hwa Song
    • 1
  • Chul-Su Yang
    • 1
  • Su-Young Kim
    • 1
  • Kil-Soo Lee
    • 1
  • A-Rum Shin
    • 1
  • Ji-Sook Lee
    • 2
  • Hae Sung Nam
    • 3
  • Hwa-Jung Kim
    • 1
  • Jeong-Kyu Park
    • 1
  • Tae-Hyun Paik
    • 2
  • Eun-Kyeong Jo
    • 1
    • 4
  1. 1.Department of Microbiology, College of MedicineChungnam National UniversityDaejeonSouth Korea
  2. 2.Department of Microbiology, College of MedicineKonyang UniversityNonsan, ChungnamSouth Korea
  3. 3.Department of Preventive Medicine, College of MedicineChungnam National UniversityDaejeonSouth Korea
  4. 4.Department of Microbiology, College of MedicineChungnam National UniversityDaejeonSouth Korea

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