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 journalArticlepeer-review

5 Scopus citations


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
Issue number8
StatePublished - Nov 2012
Externally publishedYes

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology


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