Role of ROS and MAPK in TPA-induced ICAM-1 expression in the myeloid ML-1 cell line

Kassim Traore, Rajni B. Sharma, C. Lynne Burek, Michael A. Trush

Research output: Contribution to journalArticlepeer-review

Abstract

Intercellular adhesion molecule 1 (ICAM-1) has been implicated in playing a key role in the mechanism of inflammatory process initiated in response to environ mental agents, and during normal hematopoietic cell differentiation. Though induction of ICAM-1 by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in myeloid cells has been reported, the molecular mechanism by which TPA upregulates ICAM-1 expression remains unclear. In the present study, we investigated the signaling mechanism associated with TPA-induced ICAM-1 expression in ML-1 cells. Herein, our microarray, flow cytometry, and Western blot analysis indicated that ICAM-1 was constitutively expressed at a low level in ML-1 cells, but its expression was further upregulated at both the mRNA and protein levels in response to TPA. ICAM-1 expression in response to TPA was inhibited by pretreatment with GF109203X [a specific inhibitor of protein kinase C (PKC)], or with PD98059 and U0126 (specific inhibitors of MEK), suggesting the importance of PKC, and Erk1/2 signaling cascades in this response. Interestingly, ICAM-1 expression in response to TPA-induced PKC activation was linked to the generation of reactive oxygen species (ROS), as pretreatment with NAC (an ROS scavenger) blocked both ErK1/2 activation and ICAM-1 expression induced by TPA. In addition, TPA-induced ICAM-1 expression was blocked by inhibition of nuclear factor-κB (NF-κB) activation following pretreatment with BAY11-7085 (a specific inhibitor of NF-κB activation). TPA-induced NF-κB activation was shown by increased degradation of IkB (NF-κB specific inhibitory protein). Together, these observations demonstrated that TPA, a potent activator of PKC, induces ICAM-1 expression via a ROS- and ERK1/2-dependent signaling mechanism in ML-1 cells.

Original languageEnglish (US)
Pages (from-to)1010-1021
Number of pages12
JournalJournal of cellular biochemistry
Volume100
Issue number4
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Keywords

  • Extracellular signal-regulated kinase
  • Intercellular adhesion molecule
  • ML-1 cells
  • Phorbol 12-myristate 13-acetate
  • Protein kinase C
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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