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Comparison of leptin- and interleukin-6-regulated expression of the rPAP gene family: evidence for differential co-regulatory signals

Daniël Broekaert (UGent) , Sven Eyckerman (UGent) , Delphine Lavens (UGent) , Annick Verhee (UGent) , Wim Waelput (UGent) , Joël Vandekerckhove (UGent) and Jan Tavernier (UGent)
(2002) EUROPEAN CYTOKINE NETWORK. 13(1). p.78-85
Author
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

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Chicago
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.
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.
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.
MLA
Broekaert, Daniël, Sven Eyckerman, Delphine Lavens, et al. “Comparison of Leptin- and Interleukin-6-regulated Expression of the rPAP Gene Family: Evidence for Differential Co-regulatory Signals.” EUROPEAN CYTOKINE NETWORK 13.1 (2002): 78–85. Print.
@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, Dani{\"e}l and Eyckerman, Sven and Lavens, Delphine and Verhee, Annick and Waelput, Wim and Vandekerckhove, Jo{\"e}l and Tavernier, Jan},
  issn         = {1148-5493},
  journal      = {EUROPEAN CYTOKINE NETWORK},
  keyword      = {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},
}

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