Extracellular Nampt (eNampt/Visfatin/PBEF) directly and indirectly stimulates ACTH and CCL2 protein secretion from isolated rat corticotropes

Celichowski P. Jopek K. Szyszka M. Milecka P. Tyczewska M. Sakhanova S. Szaflarski W. Malendowicz L.K. Ruciński M.
August 2021 Wroclaw Medical University

Advances in Clinical and Experimental Medicine
2021 #30 Issue 9

Background. Nicotinamide phosphoribosyltransferase (Nampt/Visfatin/PBEF) acts both as an enzyme in the nicotinamide adenine dinucleotide (NAD) synthesis pathway as well as an extracellular hormone (eNampt). Among its effects, eNampt exerts potent pro-inflammatory effects. We have recently shown that, in rats, eNampt stimulates corticosterone secretion by acting through the pituitary rather than the hypothalamus. Objectives. To investigate the mechanism of action of eNampt on the secretion of adrenocorticotropic hormone (ACTH) and chemokine (C-C motif) ligand 2 (CCL2), which are cytokines secreted by pituitary neuroendocrine tumors. Materials and methods. The research was carried out on the AtT-20 murine cell line, primary rat pituitary cell culture, isolated pituitary corticotropes, and in vivo. The effects of the performed experiments were examined using the following methods: gene expression profiling using microarrays, quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Results. The results suggest that eNampt stimulates ACTH secretion from rat corticotropes both directly and indirectly. Indirect action most likely occurs through interleukin (IL)-6 secreted by folliculostellate cells of the pituitary gland. In isolated ACTH cells of the rat pituitary gland, eNampt stimulates the expression of genes involved in the immune response. Among them, the protein encoded by the CCL2 gene seems to also be involved in the regulation of corticotropin-releasing hormone (CRH)-dependent metabolism. Unlike rat corticotropes, murine AtT-20 corticotropic cells do not react to either eNampt or Fk866 (the inhibitor of Nampt enzymatic action). Conclusions. eNampt stimulates the secretion of ACTH from rat corticotropes indirectly and directly, likely by stimulating IL-6 secretion from folliculostellate cells of the pituitary gland. This effect was not observed in the AtT-20 corticotropic cell cancer cell line.

ACTH , CCL2 , IL-6 , Nampt , Pituitary gland

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Department of Histology and Embryology, Poznan University of Medical Sciences, Poland
Regional Blood Center, Poznan University of Medical Sciences, Poland
Department of Anatomy and Histology, University of Zielona Góra, Poland
Scientific-Practical Center, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan

Department of Histology and Embryology
Regional Blood Center
Department of Anatomy and Histology
Scientific-Practical Center

10 лет помогаем публиковать статьи Международный издатель

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