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- Newly Identified CpG ODNs, M5-30 and M6-395, Stimulate MouseNewly Identified CpG ODNs, M5-30 and M6-395, Stimulate Mouse Immune Cells to Secrete TNF-α and Enhance Th1-Mediated Immunity
- Sun-Shim Choi , Eunkyung Chung , Yu-Jin Jung
- J. Microbiol. 2010;48(4):512-517. Published online August 20, 2010
- DOI: https://doi.org/10.1007/s12275-010-0053-6
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- 13 Citations
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Abstract
- Bacterial CpG motifs are known to induce both innate and adaptive immunity in infected hosts via toll-like receptor 9 (TLR9). Because small oligonucleotides (ODNs) mimicking bacterial CpG motifs are easily synthesized, they have found use as immunomodulatory agents in a number of disease models. We have developed a novel bioinformatics approach to identify effective CpG ODN sequences and evaluate their function as TLR9 ligands in a murine system. Among the CpG ODNs we identified, M5-30 and M6-395 showed significant ability to stimulate TNF-α and IFN-γ production in a mouse macrophage cell line and mouse splenocytes, respectively. We also found that these CpG ODNs activated cells through the canonical NF-κB signaling pathway. Moreover, both CpG ODNs were able to induce Th1-mediated immunity in Mycobacterium tuberculosis (Mtb)-infected mice. Our results demonstrate that M5-30 and M6-395 function as TLR9-specific ligands, making them useful in the study of TLR9 functionality and signaling in mice.
- Tumor Necrosis Factor Receptor (TNFR)-associated factor 2 (TRAF2) is not Involved in GM-CSF mRNA Induction and TNF-Mediated Cytotoxicity
- Kim, Jung Hyun , Cha, Myung Hoon , Lee, Tae Kon , Seung, Hyo Jun , Park, Choon Sik , Chung, Il Yup
- J. Microbiol. 1999;37(2):111-116.
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Abstract
- Tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) is known to act as a signal transducer that connects TNFR2 to its downstream effector functions such as proliferation of thymocytes, regulation of gene expression, and cell death. TRAF2 consists of largely two domains, the N-terminal half that contains a signal-emanating region and the C-terminal half that is responsible for binding to the intracellular region of TNFR2. In this study, we examined the possible roles of TRAF2 in granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression and cell death. A truncated mutant of TRAF2 (Δ2-263) that contains only a C-terminal half was generated, and transiently transfected to the A549 cell, a human lung cancer cell line, and L929 cell, a murine TNF-sensitive cell line. GM-CSF mRNA was induced in untransfected A540 cells both in dose- and time-dependent manner upon the exposure of TNF. However, neither the full length TRAF2 nor the mutant altered GM-CSF mRNA production regardless of the presence or absence of TNF. Furthermore, neither TRAF2 versions significantly changed the cytotoxic effect of TNF on L929 cells. These data suggest that TRAF2 may not be involved in the signal transduction pathway for GM-CSF gene induction and cell death mediated by TNF.
- Expression of Chemokine and Tumor Necrosis Factor Alpha Genes in Murine Peritoneal Macrophages Infected with Orientia tsutsugamushi
- Young-Sang Koh
- J. Microbiol. 2001;39(3):186-194.
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Abstract
- Scrub typhus, caused by Orientia tsutsugamushi infection, is clinically and histopathologically characterized by local as well as systemic inflammatory reactions, indicating that orientiae induce mechanisms that amplify the inflammatory response. To reveal underlying mechanisms of chemoattraction and activation of responding leukocytes, expression of chemokine and tumor necrosis factor alpha (TNF-[alpha]) genes in murine peritoneal macrophages after infection with the obligate intracellular bacterium O. tsutsugamushi was investigated. The genes that were upregulated included macrophage inflammatory proteins 1[alpha]/[beta] (MIP-1[alpha]/[beta]), MIP-2, monocyte chemoattractant protein 1 (MCP-1), RANTES (regulated upon activation, normal T-cell expressed and secreted), gamma-interferon-inducible protein 10 (IP-10), and TNF-[alpha]. Peak expression of these chemokines and TNF-[alpha] was observed between 1 and 3 h after infection. These responses returned to or approached baseline preinfection levels 6 h after challenge. Semiquantitative reverse transcription (RT)-PCR analysis revealed dramatic increases during infection in the steady-state levels of mRNA coding for the inhibitory subunit of NF-[kappa]B (I[kappa]B[alpha]), whose transcription is enhanced by binding of NF-[kappa]B within the I[kappa]B[alpha] promoter region. Thus, O. tsutsugamushi appears to be a strong inducer of chemokines and TNF-[alpha] which may significantly contribute to inflammation and tissue damage observed in scrub typhus by attracting and activating phagocytic leukocytes.
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