Tumor necrosis factor ? down-regulates expression of the ?1(I) collagen gene in rat hepatic stellate cells through a p20C/EBP?- and C/EBP?-dependent mechanism

Tumor necrosis factor ? (TNF-?) is one of the key cytokines of the acute phase response and of many inflammatory processes. This cytokine has several antifibrogenic actions and down-regulates the expression of the type I collagen genes and induces the expression of metalloproteinases. Because TNF-? directly antagonizes some fibrogenic actions of transforming growth factor ?1 (TGF-?1), we considered it important to map the cis-acting regulatory element of the ?1(I) collagen (col1a1) promoter involved in TNF- ? responsiveness in hepatic stellate cells (HSC), to investigate the transcription factors that bind to it, and to establish possible mechanisms by which TNF-? downregulates its expression. In this article, we show the presence of a functional TNF-?-responsive element (TaRE) in the -378 to -345 region of the col1a1 promoter. This element colocalizes with a previously reported TGF-?1-responsive element. We further demonstrate that TNF-? induces nuclear translocation and binding of transcriptional complexes containing p20C/EBP?, p35C/EBP?, and C/EBP? to this sequence of the promoter. Transient overexpression of C/EBP? or p20C/EBP?, the natural dominant negative form of C/EBP? in HSC, down-regulated activity of a CAT reporter vector driven by -412 to +110 of the col1a1 promoter. Taken together, these data suggest that the -378 to -340 region of the col1a1 promoter is the site of convergence of different stimuli that ultimately modulate col1a1 gene transcription

Tumor necrosis factor α down-regulates expression of the α1(I) collagen gene in rat hepatic stellate cells through a p20C/EBPβ- and C/EBPδ-dependent mechanism

Tumor necrosis factor α (TNF-α) is one of the key cytokines of the acute phase response and of many inflammatory processes. This cytokine has several antifibrogenic actions and down-regulates the expression of the type I collagen genes and induces the expression of metalloproteinases. Because TNF-α directly antagonizes some fibrogenic actions of transforming growth factor β1 (TGF-β1), we considered it important to map the cis-acting regulatory element of the α1(I) collagen (col1a1) promoter involved in TNF- α responsiveness in hepatic stellate cells (HSC), to investigate the transcription factors that bind to it, and to establish possible mechanisms by which TNF-α downregulates its expression. In this article, we show the presence of a functional TNF-α-responsive element (TaRE) in the -378 to -345 region of the col1a1 promoter. This element colocalizes with a previously reported TGF-β1-responsive element. We further demonstrate that TNF-α induces nuclear translocation and binding of transcriptional complexes containing p20C/EBPβ, p35C/EBPβ, and C/EBPδ to this sequence of the promoter. Transient overexpression of C/EBPδ or p20C/EBPβ, the natural dominant negative form of C/EBPβ in HSC, down-regulated activity of a CAT reporter vector driven by -412 to +110 of the col1a1 promoter. Taken together, these data suggest that the -378 to -340 region of the col1a1 promoter is the site of convergence of different stimuli that ultimately modulate col1a1 gene transcription

Relationship marketing and university-industry linkages: A conceptual framework

Copyright © 2005 by SAGE PublicationsRelationship marketing (RM) is a prolific area of current marketing theory development. While RM principles are relevant to a range of business-to-consumer and business-to-business contexts, their theoretical foundations have principally emerged in reference to the private sector. By contrast, this exploratory study examines RM opportunities between entities operating in different sectors, namely university and industry in Australia. Using a qualitative approach, findings led to the development of a conceptual framework of university-industry relationships, integrating variables of organizational environment difference, relationship and value. Overall, this exploratory study broadens RM theory and application to relationships involving parties from fundamentally different organizational environments and suggest opportunities for the implementation of RM in this context. The article concludes with recommendations for academics and practitioners and provides several directions for future research.Carolin Plewa, Pascale Quester and Thomas Baake