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Neuroimmunoendocrine Regulation of the Prion Protein in Neutrophils

Mariante, Rafael M. ; Nóbrega, Alberto ; Martins, Rodrigo A.P. ; Areal, Rômulo B. ; Bellio, Maria ; Linden, Rafael

The Journal of biological chemistry, 2012-10, Vol.287 (42), p.35506-35515 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Neuroimmunoendocrine Regulation of the Prion Protein in Neutrophils
Autor: Mariante, Rafael M. ; Nóbrega, Alberto ; Martins, Rodrigo A.P. ; Areal, Rômulo B. ; Bellio, Maria ; Linden, Rafael
Assuntos: Animals ; Gene Expression Regulation ; Glucocorticoids ; Glucocorticoids - genetics ; Glucocorticoids - immunology ; Glucocorticoids - metabolism ; Hypothalamo-Hypophyseal System - immunology ; Hypothalamo-Hypophyseal System - metabolism ; Hypothalamo-Hypophyseal System - pathology ; Immunology ; Inflammation ; Inflammation - chemically induced ; Inflammation - genetics ; Inflammation - immunology ; Inflammation - metabolism ; Inflammation - pathology ; Lipopolysaccharides - pharmacology ; Mice ; Mice, Knockout ; Neutrophil ; Neutrophils - immunology ; Neutrophils - metabolism ; Neutrophils - pathology ; Pituitary-Adrenal System - immunology ; Pituitary-Adrenal System - metabolism ; Pituitary-Adrenal System - pathology ; Prion Diseases - genetics ; Prion Diseases - immunology ; Prion Diseases - metabolism ; Prions ; Protein Biosynthesis - drug effects ; Protein Biosynthesis - genetics ; Protein Biosynthesis - immunology ; PrPC Proteins - biosynthesis ; PrPC Proteins - genetics ; PrPC Proteins - immunology ; Stress ; Stress, Physiological ; Transcription, Genetic - drug effects ; Transcription, Genetic - genetics ; Transcription, Genetic - immunology ; Transforming Growth Factor beta - genetics ; Transforming Growth Factor beta - immunology ; Transforming Growth Factor beta - metabolism
É parte de: The Journal of biological chemistry, 2012-10, Vol.287 (42), p.35506-35515
Notas: Present address: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Descrição: The prion protein (PrPC) is a cell surface protein expressed mainly in the nervous system. In addition to the role of its abnormal conformer in transmissible spongiform encephalopathies, normal PrPC may be implicated in other degenerative conditions often associated with inflammation. PrPC is also present in cells of hematopoietic origin, including T cells, dendritic cells, and macrophages, and it has been shown to modulate their functions. Here, we investigated the impact of inflammation and stress on the expression and function of PrPC in neutrophils, a cell type critically involved in both acute and chronic inflammation. We found that systemic injection of LPS induced transcription and translation of PrPC in mouse neutrophils. Up-regulation of PrPC was dependent on the serum content of TGF-β and glucocorticoids (GC), which, in turn, are contingent on the activation of the hypothalamic-pituitary-adrenal axis in response to systemic inflammation. GC and TGF-β, either alone or in combination, directly up-regulated PrPC in neutrophils, and accordingly, the blockade of GC receptors in vivo curtailed the LPS-induced increase in the content of PrPC. Moreover, GC also mediated up-regulation of PrPC in neutrophils following noninflammatory restraint stress. Finally, neutrophils with up-regulated PrPC presented enhanced peroxide-dependent cytotoxicity to endothelial cells. The data demonstrate a novel interplay of the nervous, endocrine, and immune systems upon both the expression and function of PrPC in neutrophils, which may have a broad impact upon the physiology and pathology of various organs and systems. Background: Prion protein (PrPC) modulates inflammation, and prion diseases affect neutrophil numbers and functions, but the regulation of PrPC in neutrophils is unknown. Results: Inflammation and stress massively up-regulated PrPC in neutrophils via glucocorticoids and TGF-β. Conclusion: We show a novel pathway of regulation of PrPC, with functional consequences for neutrophils. Significance: Systemic control of the expression and function of PrPC broadly modulates cellular physiology and pathology.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Neuroimmunoendocrine Regulation of the Prion Protein in Neutrophils

Mariante, Rafael M. ; Nóbrega, Alberto ; Martins, Rodrigo A.P. ; Areal, Rômulo B. ; Bellio, Maria ; Linden, Rafael

United States: Elsevier Inc

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