Comparative study of gp130 cytokine effects on corticotroph AtT-20 cells - Redundancy or specificity of neuroimmunoendocrine modulators?

Auernhammer, Christoph J.; Kopp, F. B.; Vlotides, G.; Dorn, F.; Isele, N. B.; Spottl, G.; Cengic, N.; Weber, M. M.; Senaldi, G. and Engelhardt, D. (2004): Comparative study of gp130 cytokine effects on corticotroph AtT-20 cells - Redundancy or specificity of neuroimmunoendocrine modulators? In: Neuroimmunomodulation, No. 4: pp. 224-232

Abstract

Objective: This comparative in vitro study examined the effects of all known gp130 cytokines on murine corticotroph AtT-20 cell function. Methods: Cytokines were tested at equimolar concentrations from 0.078 to 10 nM. Tyrosine phosphorylation of the signal transducer and activator of transcription ( STAT) 3 and STAT1, the STAT-dependent suppressor of cytokine signaling (SOCS)-3 promoter activity, SOCS-3 gene expression, STAT-dependent POMC promoter activity and adrenocorticotropic hormone ( ACTH) secretion were determined. Results: Leukemia inhibitory factor (LIF), human oncostatin M (OSM) and cardiotrophin (CT)-1 (LIFR/gp130 ligands), as well as ciliary neurotrophic factor ( CNTF) and novel neurotrophin1/B-cell stimulating factor-3 (CNTFRalpha/LIFR/gp130 ligands) are potent stimuli of corticotroph cells in vitro. In comparison, interleukin (IL)-6 (IL-6R/gp130 ligand) and IL-11 (IL-11R/gp130 ligand) exhibited only modest direct effects on corticotrophs, while murine OSM (OSMR/gp130 ligand) showed no effect. Conclusion: (i) CNTFR complex ligands are potent stimuli of corticotroph function, comparable to LIFR complex ligands; (ii) IL-6 and IL-11 are relatively weak direct stimuli of corticotroph function; (iii) differential effects of human and murine OSM suggest that LIFR/gp130 (OSMR type I) but not OSMR/gp130 (OSMR type II) are involved in corticotroph signaling. (iv) CT-1 has the hitherto unknown ability to stimulate corticotroph function, and (v) despite redundant immuno-neuroendocrine effects of different gp130 cytokines, corticotroph cells are preferably activated through the LIFR and CNTFR complexes. Copyright (C) 2004 S. Karger AG, Basel.

• Item Type: Journal article
• Form of publication: Publisher's Version
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1021-7401
• Alliance/National Licence: This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
• Language: English