Hypoxia, but not reoxygenation, induces interleukin 6 gene expression through NF-κB activation

Kei Ichi Muraoka, Kouichi Shimizu, Xiangao Sun, Yong Kang Zhang, Takashi Tani, Tetsuo Hashimoto, Masao Yagi, Itsuo Miyazaki, Ken Ichi Yamamoto

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)


Interleukin (IL) 6 is one of major mediators of inflammation, and IL-6 gene activation during hypoxia/reoxygenation has been implicated in the pathogenesis of ischemia/reperfusion injury. However, molecular events involved in IL-6 gene expression during hypoxia/reoxygenation remain to be identified. We have previously shown that NF-κB plays an essential and indispensable role in the transcriptional activation of the IL-6 gene induced by various stimuli, including IL-1 and tumor necrosis factor-α. We show here that hypoxia, but not reoxygenation, induces the activation of NF-κB through the degradation of a major inhibitor of NF-κB, IκBα. This hypoxia-induced NF-κB activation resulted in the κB-dependent transcriptional activation of the IL-6 gene. Interestingly, the time course of hypoxia-induced NF-κB activation was rather slow as compared with those of NF-κB activation induced by other stimuli, such as IL-1: a significant NF-κB activation was not observed before 1 hr of hypoxia treatment and persisted fur up to 7 hr of hypoxia treatment. However, hypoxia-induced NF-κB activation was not inhibited by cycloheximide, which indicates that hypoxia directly triggers NF-κB activation. Furthermore, while hypoxia is unlikely to generate reactive oxygene intermediates, pretreatment of cells with antioxidants such as N-acetyl cysteine and α-tocopherol inhibited NF-κB activation induced by hypoxia. Thus, we discuss possible implications of these results for a postulated role of reactive oxygene intermediates in NF-κB activation.

Original languageEnglish
Pages (from-to)466-470
Number of pages5
Issue number3
Publication statusPublished - Feb 15 1997
Externally publishedYes

ASJC Scopus subject areas

  • Transplantation


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