Biomedical Engineering Reference
In-Depth Information
6
CHAPTER
The PI3K/Akt-NF-kappa B Signaling
Pathway and Hypoxia-induced
Mitogenic Factor in Vascular Adhesion
Molecule 1 Gene Expression
Dechun Li
‡
MD, PhD, Associate Professor, Department of Internal Medicine, Division of
Pulmonary, Critical Care and Sleep Medicine, Saint Louis University, Room R110,
Doisy Hall, St. Louis, MO 63104, E-mail:
dli2@slu.edu
7th Floor, Desloge Towers, St. Louis, MO 63110-2539
ABSTRACT
h e phosphoinositide 3-kinase (PI3K) signaling transduction pathways play
critical roles in regulating cellular activation, inl ammatory responses, chemotaxis,
and apoptosis; and NF-κB has been demonstrated to be a pivotal downstream
transcription factor in adhesion molecule gene upregulation induced by cytokine
or inl ammatory agents. In particular, most of the adhesion molecule genes have
NF-κB binding site in their promoter regions, indicating the signii cance of this
signaling transduction pathway in the regulation of adhesion molecule gene
expression in inl ammatory cells and vascular endothelium. Activation of the
PI3K/Akt-NF-κB signaling pathways in response to inl ammatory stimuli will
modify the expression levels of adhesion molecules in both leukocytes and vascular
endothelium resulting in a coordinated process to facilitate the extravasation of
specialized leukocytes into the inl ammatory foci. We have discovered that the
cytokine-like protein hypoxia-induced mitogenic factor (HIMF) stimulates the
endogenous PI3K/Akt signaling pathways and promotes the activation of NF-κB.
h e latter directly binds to the VCAM-1 promoter and signii cantly enhances
Key terms are dei ned at the end of the chapter.
