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Neuroimmunomodulation. 2004;11(4):224-32.

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

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1
Medizinische Klinik II, Klinikum Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany. Christoph.Auernhammer@med2.med.uni-muenchen.de

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 neurotrophin-1/B-cell stimulating factor-3 (CNTFR alpha/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.

PMID:
15249728
DOI:
10.1159/000078440
[Indexed for MEDLINE]

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