Signal Transduction Pathways of Inflammatory Gene Expressions and Therapeutic Implications

Title: Signal Transduction Pathways of Inflammatory Gene Expressions and Therapeutic Implications

Volume: 12 Issue: 27

Author(s): Ching-Chow Chen

Affiliation:

Keywords: ICAM-1, COX-2, C-Src, tyrosine kinase inhibitors, STAT-1

Abstract: Intercellular adhesion molecule-1 (ICAM-1), an inducible cell adhesion glycoprotein of the immunoglobulin supergene family and cyclooxygenase-2 (COX-2), an inducible prostaglandin G/H synthase, are overexpressed by proinflammatory mediators in a wide variety of cell types. These stimuli increase ICAM-1 or COX-2 expression primarily through activation of ICAM-1 or COX-2 gene transcription. The architecture of the ICAM-1 or COX-2 promoter is complex, containing a large number of binding site for inducible transcription factors, the most important of which is NF-κB. NF-κB acts in concert with other transcription factors or transcriptional coactivators which facilitate the assembly of distinct stereospecific transcription complexes on the ICAM-1 or COX-2 promoter. These transcription complexes presumably mediate the induction of ICAM-1 or COX-2 expression in different cell types and in response to different stimuli. In this review, I summarize the current understanding of ICAM-1 and COX-2 gene regulation with a particular emphasis on the transcription factors or coactivators, and signal transduction pathways critical for their expression. A PKC-dependent c-Src pathway activating NF-κB or GAS to enhance ICAM-1 or COX-2 gene expression is discussed. Furthermore, natural products and novel agents targeting on the transcription factor with potential anti-inflammation and anti-tumor activity are also discussed.

Cite this article as:

Chen Ching-Chow, Signal Transduction Pathways of Inflammatory Gene Expressions and Therapeutic Implications, Current Pharmaceutical Design 2006; 12 (27) . https://dx.doi.org/10.2174/138161206778343028