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

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.