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

✍ Scribed by Kassim Traore; Rajni B. Sharma; C. Lynne Burek; Michael A. Trush

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 424 KB
• Volume: 100
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21101

✦ Synopsis

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 environmental 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. J. Cell. Biochem. 100: 1010–1021, 2007. © 2006 Wiley‐Liss, Inc.