VCAM-1 is a cytokine inducible, endothelial leukocyte adhesion molecule. It specifically binds the integrin VLA4, which is restricted to monocytes, lymphocytes, eosinophils and basophils but is not present on neutrophils. Immunohistochemical techniques reveal endothelial VCAM-1 expression associated with a variety of inflammatory processes including vasculitic lesions, chronic vascular graft rejection, and early atherosclerosis. The laboratory has begun preliminary efforts to elucidate the molecular mechanisms controlling VCAM-1 response to cytokine and tissue specific expression. This proposal involves three lines of investigation and will expand upon previous experiments. First, analysis of novel functional elements in the promoter region of the VCAM1 gene to better understand the DNA-protein interactions that mediate the transcriptional regulation of VCAM1. Second, characterization of the DNA binding and transactivating properties of a novel transcription factor. The candidate factor was obtained by screening an expression library with a recognition site sequence contained within the VCAM1 promoter. Third, utilization of characterized promoter sequences as transgenes to allow a more stringent evaluation of the temporal and spatial (cell-type specific) expression pattern of VCAM1. Elucidation of the mechanisms governing VCAM-1 expression will further our understanding of the inflammatory response and possibly suggest points of intervention.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003011-06
Application #
2776532
Study Section
Research Training Review Committee (RTR)
Project Start
1994-03-01
Project End
2000-02-29
Budget Start
1998-03-01
Budget End
2000-02-29
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Emory University
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Neish, A S; Anderson, S F; Schlegel, B P et al. (1998) Factors associated with the mammalian RNA polymerase II holoenzyme. Nucleic Acids Res 26:847-53
Neish, A S; Read, M A; Thanos, D et al. (1995) Endothelial interferon regulatory factor 1 cooperates with NF-kappa B as a transcriptional activator of vascular cell adhesion molecule 1. Mol Cell Biol 15:2558-69
Collins, T; Read, M A; Neish, A S et al. (1995) Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J 9:899-909
Read, M A; Neish, A S; Luscinskas, F W et al. (1995) The proteasome pathway is required for cytokine-induced endothelial-leukocyte adhesion molecule expression. Immunity 2:493-506
Neish, A S; Khachigian, L M; Park, A et al. (1995) Sp1 is a component of the cytokine-inducible enhancer in the promoter of vascular cell adhesion molecule-1. J Biol Chem 270:28903-9