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Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes
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Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes

Published on: May 31, 2018

Mitogen-activated protein kinases are involved in tumor necrosis factor alpha production in macrophages infected with

Ji-Hyun Yun1, Jung-Eun Koo, Young-Sang Koh

  • 1Department of Microbiology, School of Medicine, BK21 Program, and Institute of Medical Science, Cheju National University, Jeju 690-756, Republic of Korea.

Microbiology and Immunology
|June 5, 2009
PubMed

Insights

Mitogen-activated protein kinase (MAPK) signaling is crucial for tumor necrosis factor-alpha (TNF-alpha) production in macrophages infected with Orientia tsutsugamushi, the bacteria causing scrub typhus.

Area of Science:

  • Immunology
  • Microbiology
  • Cellular Biology

Background:

  • Orientia tsutsugamushi is the bacterium responsible for scrub typhus.
  • Tumor necrosis factor-alpha (TNF-alpha) plays a key role in the host immune response to bacterial infections.
  • Mitogen-activated protein kinases (MAPKs) are critical signaling pathways involved in cellular responses to stimuli.

Purpose of the Study:

  • To investigate the role of MAPK signaling pathways in TNF-alpha production by macrophages following O. tsutsugamushi infection.
  • To elucidate the specific MAPK pathways involved and their regulatory mechanisms (transcriptional vs. post-transcriptional).

Main Methods:

  • Macrophages were infected with O. tsutsugamushi.
  • Phosphorylation of ERK1/2, JNK, and p38 MAPK was assessed.
  • Selective MAPK inhibitors were used to evaluate their effect on TNF-alpha production.
  • Mechanisms of TNF-alpha regulation (transcriptional and post-transcriptional) were analyzed.

Main Results:

  • O. tsutsugamushi infection led to the phosphorylation of ERK1/2, JNK, and p38 MAPK in macrophages.
  • Inhibition of these MAPK pathways significantly reduced O. tsutsugamushi-induced TNF-alpha production.
  • The p38 and JNK pathways regulated TNF-alpha production via post-transcriptional mechanisms.
  • The ERK pathway primarily controlled the transcriptional regulation of TNF-alpha gene expression.

Conclusions:

  • MAPK signaling pathways are essential for maximal TNF-alpha production in macrophages during O. tsutsugamushi infection.
  • Different MAPK pathways (ERK, JNK, p38) contribute distinctly to TNF-alpha regulation at both transcriptional and post-transcriptional levels.
  • Understanding these mechanisms could inform therapeutic strategies against scrub typhus.

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