Regulation of human airway epithelial cell IL-8 expression by MAP kinases

Jing Li, Sreedharan Kartha, Svetlana Iasvovskaia, Alan Tan, Rajesh K. Bhat, Joel M. Manaligod, Kristen Page, Allan R. Brasier, Marc B. Hershenson

Research output: Contribution to journalReview article

122 Scopus citations

Abstract

Recent studies indicate that maximal IL-8 protein expression requires activation of NF-κB as well as activation of the MAP kinases ERK, JNK, and p38. However, the precise relationship between NF-κB transactivation and MAP kinase activation remains unclear. We examined the requirements of NF-κB, ERK, JNK, and p38 for TNF-α-induced transcription from the IL-8 promoter in a human bronchial epithelial cell line. Treatment with TNF-α induced activation of all three MAP kinases. Using a combination of chemical and dominant-negative inhibitors, we found that inhibition of NF-κB, ERK, and JNK, but not p38, each decreased TNF-α-induced transcription from the IL-8 promoter. Inhibition of JNK signaling also substantially reduced TNF-α-induced NF-κB transactivation, whereas inhibition of ERK and p38 had no effect. On the other hand, ERK was required and sufficient for TNF-α-induced activation of activator protein (AP)-1 promoter sequences, which together function as a basal level enhancer. JNK activation was also required for AP-1 transactivation. Finally, inhibition of p38 attenuated IL-8 protein abundance, suggesting that p38 regulates IL-8 expression in a posttranscriptional manner. We conclude that, in human airway epithelial cells, MAP kinases may regulate IL-8 promoter activity by NF-κB-dependent (in the case of JNK) and -independent (ERK) processes, as well as by posttranscriptional mechanisms (p38).

Original languageEnglish (US)
Pages (from-to)L690-L699
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume283
Issue number4 27-4
StatePublished - Oct 1 2002

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Keywords

  • Cytokines
  • Inflammation
  • Interleukin 8
  • Mitogen-activated protein
  • Signal transduction
  • Transcription factors

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Li, J., Kartha, S., Iasvovskaia, S., Tan, A., Bhat, R. K., Manaligod, J. M., Page, K., Brasier, A. R., & Hershenson, M. B. (2002). Regulation of human airway epithelial cell IL-8 expression by MAP kinases. American Journal of Physiology - Lung Cellular and Molecular Physiology, 283(4 27-4), L690-L699.