Crosstalk between JNK and NF-κB in the KDO2-mediated production of TNFα in HAPI cells.

Xuexing Zheng, Wenwen Zheng, Shue Liu, Harshil M. Patel, Xianzhu Xia, Hongsheng Ouyang, Roy C Levitt, Keith A Candiotti, Shuanglin Hao

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Both nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases mediate production of proinflammatory cytokines in many types of cells. c-Jun N-terminal kinases (JNK) is a key regulator of many cellular events including cell inflammation and/or programmed cell death (apoptosis). In addition to mediating immune and inflammatory responses, NF-κB transcription factors control cell survival. It is reported that activation of NF-κB antagonizes apoptosis or programmed cell death by numerous triggers. It has been reported that NF-κB activation results in rapid inactivation of JNK in tumor necrosis factor alpha (TNFα)-treated murine embryonic fibroblasts. It is not clear about the relationship of JNK and NF-κB in the microglial cells induced by TLR4 activity. In the present study, we investigated the relationship of JNK and NF-κB in the highly aggressively proliferating immortalized microglial cell line treated with KDO2 (a TLR4 agonist). KDO2 treatment significantly induced the phosphorylation of JNK and NF-κB, and released TNFα. Knockdown of TLR4 with TLR4 siRNA significantly reduced phosphorylation of JNK (pJNK), phosphorylation of NF-κB, and release of TNFα. Inhibition of JNK reduced the release of TNFα, but not phosphorylation of NF-κB. Unexpectedly, inhibition of NF-κB enhanced pJNK and the release of TNFα. These results showed that TNFα induced by KDO2 was JNK-dependent, and that NF-κB negatively modulated both pJNK and TNFα in the cultured microglial cell line. The current study may provide a new insight in the modulation of TNFα in the microglial cell line.

Original languageEnglish (US)
Pages (from-to)1375-1383
Number of pages9
JournalCellular and Molecular Neurobiology
Volume32
Issue number8
StatePublished - 2012
Externally publishedYes

Fingerprint

Tumor Necrosis Factor-alpha
NF-kappa B
Phosphorylation
Cell Line
Cell Death
Phosphotransferases
Apoptosis
NF-kappa B kinase
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Small Interfering RNA
Cultured Cells
Cell Survival
Transcription Factors
Fibroblasts
Cytokines
Inflammation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Zheng, X., Zheng, W., Liu, S., Patel, H. M., Xia, X., Ouyang, H., ... Hao, S. (2012). Crosstalk between JNK and NF-κB in the KDO2-mediated production of TNFα in HAPI cells. Cellular and Molecular Neurobiology, 32(8), 1375-1383.

Crosstalk between JNK and NF-κB in the KDO2-mediated production of TNFα in HAPI cells. / Zheng, Xuexing; Zheng, Wenwen; Liu, Shue; Patel, Harshil M.; Xia, Xianzhu; Ouyang, Hongsheng; Levitt, Roy C; Candiotti, Keith A; Hao, Shuanglin.

In: Cellular and Molecular Neurobiology, Vol. 32, No. 8, 2012, p. 1375-1383.

Research output: Contribution to journalArticle

Zheng X, Zheng W, Liu S, Patel HM, Xia X, Ouyang H et al. Crosstalk between JNK and NF-κB in the KDO2-mediated production of TNFα in HAPI cells. Cellular and Molecular Neurobiology. 2012;32(8):1375-1383.
Zheng, Xuexing ; Zheng, Wenwen ; Liu, Shue ; Patel, Harshil M. ; Xia, Xianzhu ; Ouyang, Hongsheng ; Levitt, Roy C ; Candiotti, Keith A ; Hao, Shuanglin. / Crosstalk between JNK and NF-κB in the KDO2-mediated production of TNFα in HAPI cells. In: Cellular and Molecular Neurobiology. 2012 ; Vol. 32, No. 8. pp. 1375-1383.
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