Comparison of leptin- and interleukin-6-regulated expression of the rPAP gene family: evidence for differential co-regulatory signals
- Author
- Daniël Broekaert (UGent) , Sven Eyckerman (UGent) , Delphine Lavens (UGent) , Annick Verhee (UGent) , Wim Waelput (UGent) , Joël Vandekerckhove (UGent) and Jan Tavernier (UGent)
- Organization
- Abstract
- The pancreatitis-associated protein (PAP)/regenerating protein (REG) family represents a complex group of small secretory proteins, which can function as acute phase reactants, lectins, antiapoptotic factors or growth factors for pancreatic beta-cells and neural cells. Transcriptional induction of rPAP/Reg genes was studied here in PC12 cells made responsive to leptin. Northern-blots showed quantitative differences in induction of four major family members by leptin and IL-6. Surprisingly, induction by leptin was strongly enhanced upon forskolin co-treatment whereas induction by IL-6 was counteracted. Functional studies involving progressive rPAP I promoter deletions showed, in the case of leptin, a clear correlation with predicted cis-regulatory elements. Leptin-induced stimulation was dependent on STAT3, since over-expression of dominant-negative STAT3, but not of dominant-negative STAT1, completely blocked transcriptional activation. In case of IL-6, an enhancer element outside the cloned promoter fragment is required for full stimulation. The effects of forskolin in a leptin and IL-6 context could not be explained at the promoter level, but rather events occurring upstream in the signalling cascade must be postulated to explain the differential co-regulatory effects.
- Keywords
- forskolin, IL-6, leptin, rPAP/Reg gene family, signal transduction, PANCREATITIS-ASSOCIATED-PROTEIN, TUMOR-NECROSIS-FACTOR, I PAP-I, MESSENGER-RNA, CHROMOSOMAL LOCALIZATION, STRUCTURAL ORGANIZATION, INSULIN-SECRETION, EARLY-RESPONSE, CELL-LINE, IDENTIFICATION
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-156258
- MLA
- Broekaert, Daniël, et al. “Comparison of Leptin- and Interleukin-6-Regulated Expression of the RPAP Gene Family: Evidence for Differential Co-Regulatory Signals.” EUROPEAN CYTOKINE NETWORK, vol. 13, no. 1, 2002, pp. 78–85.
- APA
- Broekaert, D., Eyckerman, S., Lavens, D., Verhee, A., Waelput, W., Vandekerckhove, J., & Tavernier, J. (2002). Comparison of leptin- and interleukin-6-regulated expression of the rPAP gene family: evidence for differential co-regulatory signals. EUROPEAN CYTOKINE NETWORK, 13(1), 78–85.
- Chicago author-date
- Broekaert, Daniël, Sven Eyckerman, Delphine Lavens, Annick Verhee, Wim Waelput, Joël Vandekerckhove, and Jan Tavernier. 2002. “Comparison of Leptin- and Interleukin-6-Regulated Expression of the RPAP Gene Family: Evidence for Differential Co-Regulatory Signals.” EUROPEAN CYTOKINE NETWORK 13 (1): 78–85.
- Chicago author-date (all authors)
- Broekaert, Daniël, Sven Eyckerman, Delphine Lavens, Annick Verhee, Wim Waelput, Joël Vandekerckhove, and Jan Tavernier. 2002. “Comparison of Leptin- and Interleukin-6-Regulated Expression of the RPAP Gene Family: Evidence for Differential Co-Regulatory Signals.” EUROPEAN CYTOKINE NETWORK 13 (1): 78–85.
- Vancouver
- 1.Broekaert D, Eyckerman S, Lavens D, Verhee A, Waelput W, Vandekerckhove J, et al. Comparison of leptin- and interleukin-6-regulated expression of the rPAP gene family: evidence for differential co-regulatory signals. EUROPEAN CYTOKINE NETWORK. 2002;13(1):78–85.
- IEEE
- [1]D. Broekaert et al., “Comparison of leptin- and interleukin-6-regulated expression of the rPAP gene family: evidence for differential co-regulatory signals,” EUROPEAN CYTOKINE NETWORK, vol. 13, no. 1, pp. 78–85, 2002.
@article{156258,
abstract = {{The pancreatitis-associated protein (PAP)/regenerating protein (REG) family represents a complex group of small secretory proteins, which can function as acute phase reactants, lectins, antiapoptotic factors or growth factors for pancreatic beta-cells and neural cells. Transcriptional induction of rPAP/Reg genes was studied here in PC12 cells made responsive to leptin. Northern-blots showed quantitative differences in induction of four major family members by leptin and IL-6. Surprisingly, induction by leptin was strongly enhanced upon forskolin co-treatment whereas induction by IL-6 was counteracted. Functional studies involving progressive rPAP I promoter deletions showed, in the case of leptin, a clear correlation with predicted cis-regulatory elements. Leptin-induced stimulation was dependent on STAT3, since over-expression of dominant-negative STAT3, but not of dominant-negative STAT1, completely blocked transcriptional activation. In case of IL-6, an enhancer element outside the cloned promoter fragment is required for full stimulation. The effects of forskolin in a leptin and IL-6 context could not be explained at the promoter level, but rather events occurring upstream in the signalling cascade must be postulated to explain the differential co-regulatory effects.}},
author = {{Broekaert, Daniël and Eyckerman, Sven and Lavens, Delphine and Verhee, Annick and Waelput, Wim and Vandekerckhove, Joël and Tavernier, Jan}},
issn = {{1148-5493}},
journal = {{EUROPEAN CYTOKINE NETWORK}},
keywords = {{forskolin,IL-6,leptin,rPAP/Reg gene family,signal transduction,PANCREATITIS-ASSOCIATED-PROTEIN,TUMOR-NECROSIS-FACTOR,I PAP-I,MESSENGER-RNA,CHROMOSOMAL LOCALIZATION,STRUCTURAL ORGANIZATION,INSULIN-SECRETION,EARLY-RESPONSE,CELL-LINE,IDENTIFICATION}},
language = {{eng}},
number = {{1}},
pages = {{78--85}},
title = {{Comparison of leptin- and interleukin-6-regulated expression of the rPAP gene family: evidence for differential co-regulatory signals}},
volume = {{13}},
year = {{2002}},
}