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Growth factors, cytokines and their receptors as downstream targets of arylhydrocarbon receptor (AhR) signaling pathways

Authors
  • Haarmann-Stemmann, Thomas
  • Bothe, Hanno
  • Abel, Josef
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Jan 01, 2008
Accepted Date
Sep 12, 2008
Volume
77
Issue
4
Pages
508–520
Identifiers
DOI: 10.1016/j.bcp.2008.09.013
Source
Elsevier
Keywords
License
Unknown

Abstract

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is a widespread environmental pollutant, which causes a variety of severe health effects, e.g. immunosuppression, hepatotoxicity, and carcinogenesis. The main mediator of TCDD toxicity is the arylhydrocarbon receptor (AhR), which, upon activation, translocates into the nucleus and enforces gene expression. Since most of the pleiotropic effects caused by TCDD are associated with alterations in cell growth and differentiation, the analysis of the interference of the AhR with factors controlling these cellular functions seems to be a promising target regarding the prevention and treatment of chemical-provoked diseases. Cell growth and differentiation are regulated by numerous growth factors and cytokines. These multifunctional peptides promote or inhibit cell growth and regulate differentiation and other cellular processes, depending on cell-type and developmental stage. They are involved in the regulation of a broad range of physiological processes, including immune response, hematopoiesis, neurogenesis, and tissue remodeling. The complex network of growth factors and cytokines is accurately regulated and disturbances of this system are associated with adverse health effects. The molecular mechanisms by which the AhR interferes with this signaling network are multifaceted and the physiological consequences of this cross-talk are quite enigmatic. The investigation of this complex interaction is an exciting task, especially with respect to the recently described non-genomic and/or ligand-independent activities of AhR. Therefore, we summarize the current knowledge about the interaction of the AhR with three cytokine-/growth factor-related signal transducers – the epidermal growth factor (EGF) family, tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) – with regard to pathophysiological findings.

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