OBJECTIVE: Endothelial cells comprise a key component of the inflammatory response. We set out to obtain a comprehensive overview of the immediate-early to early gene expression program of interleukin-1 (IL-1)-stimulated endothelial cells and to identify novel transcription factors and regulatory elements. METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were stimulated with IL-1 for 0, 0.5, 1, 2.5, and 6 hours and analyzed using Affymetrix U133 microarrays. A total of 137 genes were found to be regulated >4-fold, including 18 transcription factors. The expression of selected genes was confirmed by real-time polymerase chain reaction. Cluster analysis was performed in order to group genes according to their expression profiles. To identify novel transcription factor-binding sites, the corresponding promoters were extracted from databases and analyzed for regulatory elements that were over-represented in specific clusters. Several potentially novel DNA binding sites were identified, and one was shown to specifically bind an IL-1-inducible protein from HUVEC. CONCLUSIONS: These results demonstrate that in the early phase after stimulation, IL-1 evokes a complex gene expression program that includes positive but also negative (feedback) regulators of diverse endothelial cell functions. Furthermore, the identification of a new promoter regulatory element demonstrates the feasibility of the bioinformatics-driven approach to discover novel regulatory mechanisms.
OBJECTIVE: Endothelial cells comprise a key component of the inflammatory response. We set out to obtain a comprehensive overview of the immediate-early to early gene expression program of interleukin-1 (IL-1)-stimulated endothelial cells and to identify novel transcription factors and regulatory elements. METHODS AND RESULTS:Human umbilical vein endothelial cells (HUVECs) were stimulated with IL-1 for 0, 0.5, 1, 2.5, and 6 hours and analyzed using Affymetrix U133 microarrays. A total of 137 genes were found to be regulated >4-fold, including 18 transcription factors. The expression of selected genes was confirmed by real-time polymerase chain reaction. Cluster analysis was performed in order to group genes according to their expression profiles. To identify novel transcription factor-binding sites, the corresponding promoters were extracted from databases and analyzed for regulatory elements that were over-represented in specific clusters. Several potentially novel DNA binding sites were identified, and one was shown to specifically bind an IL-1-inducible protein from HUVEC. CONCLUSIONS: These results demonstrate that in the early phase after stimulation, IL-1 evokes a complex gene expression program that includes positive but also negative (feedback) regulators of diverse endothelial cell functions. Furthermore, the identification of a new promoter regulatory element demonstrates the feasibility of the bioinformatics-driven approach to discover novel regulatory mechanisms.
Authors: C Hamid; K Norgate; D P D'Cruz; M A Khamashta; M Arno; J D Pearson; G Frampton; J J Murphy Journal: Ann Rheum Dis Date: 2007-01-12 Impact factor: 19.103
Authors: Mark A Rainey; Manju George; GuoGuang Ying; Reiko Akakura; Daniel J Burgess; Ed Siefker; Tom Bargar; Lynn Doglio; Susan E Crawford; Gordon L Todd; Venkatesh Govindarajan; Rex A Hess; Vimla Band; Mayumi Naramura; Hamid Band Journal: BMC Dev Biol Date: 2010-04-02 Impact factor: 1.978
Authors: Lee W Ott; Katheryn A Resing; Alecia W Sizemore; Joshua W Heyen; Ross R Cocklin; Nathan M Pedrick; H Cary Woods; Jake Y Chen; Mark G Goebl; Frank A Witzmann; Maureen A Harrington Journal: J Proteome Res Date: 2007-05-16 Impact factor: 4.466
Authors: Florian Gruber; Herbert Mayer; Barbara Lengauer; Veronika Mlitz; John M Sanders; Alexandra Kadl; Martin Bilban; Rainer de Martin; Oswald Wagner; Thomas W Kensler; Masayuki Yamamoto; Norbert Leitinger; Erwin Tschachler Journal: FASEB J Date: 2009-08-31 Impact factor: 5.191