Regulation of interleukin-6 secretion in murine pituicytes

Abstract

Pituicytes, the astrocytic glial cells of the neural lobe, are known to secrete interleukin-6 and nitric oxide upon stimulation with various inflammatory mediators, i.e. interleukin-1β. Nitric oxide is described to modulate the secretion of interleukin-6 in various cell types. The aim of the present study was to investigate the effect of nitric oxide on interleukin-1β induced interleukin-6 secretion. Furthermore the effect of interferon-γ on interleukin-6 and nitric oxide release was investigated. Cultures of pituicytes were prepared of neural lobes from male mice. The effect of interleukin-1β and interferon-γ on interleukin-6 and nitric oxide secretion was investigated in pituicytes cultured for 14 days. The secretion of interleukin-6 and nitric oxide was determined after 24 h of stimulation. Pituicytes secrete interleukin-6 upon stimulation with interleukin-1β dose dependently but did not induce any detectable nitric oxide release. Co-stimulation with interferon-γ and interleukin-1β induced a significant nitric oxide release. In addition interferon-γ inhibits interleukin-1β induced interleukin-6 secretion dose dependently. The observed effect of interferon-γ on interleukin-6 secretion was not affected by the specific inducible nitric oxide synthase inhibitor 1400W (N-(3-[aminomethyl]benzyl)acetamidine). Furthermore interferon-γ dose dependently inhibits unstimulated interleukin-6 secretion. Use of the nitric oxide releaser DETA/NO (2,2′-(hydroxynitrosohydrazono)bis-ethanimine) demonstrated that nitric oxide does not inhibit interleukin-1β induced interleukin-6 secretion.These results demonstrated that nitric oxide has no influence on interleukin-1β induced interleukin-6 secretion in cultured pituicytes. However the results are showing that interferon-γ has an inhibitory effect on interleukin-6 secretion.