Proinflammatory cytokines (tumor necrosis factor and interleukin 1) stimulate release of high mobility group protein-1 by pituicytes.
BACKGROUND
Cytokines mediate the metabolic and physiologic responses to injury and infection. Anterior pituitary cells express receptors for tumor necrosis factor (TNF) and interleukin 1 (IL-1), which can signal these cells to release corticotropin, growth hormone, and cytokines such as IL-1 and macrophage migration inhibitory factor. This interaction provides an important link between the immune system and the neuroendocrine system. We reasoned that pituicytes activated with TNF or IL-1 might release previously unrecognized factors that could participate in this signaling from the neuroendocrine to the immune system.


METHODS
Proteins released from rat pituicytes (GH3) after stimulation with proinflammatory cytokines were identified by N-terminal amino acid sequencing. Polyclonal antibodies against a peptide corresponding to the N-terminal amino acid sequence were generated and used to determine the kinetics of protein release.


RESULTS
Cytokine stimulation induced the release of a 30-kd protein from rat pituicytes. After the protein was isolated and the N-terminal amino acid sequence determined, a protein database analysis revealed that it is high mobility group-1 (HMG-1) protein. TNF and IL-1 induced the release of HMG-1 from pituicytes in a time- and dose-dependent manner. Interferon gamma alone did not induce the release of HMG-1, but it enhanced TNF-induced HMG-1 release.


CONCLUSIONS
Stimulation of pituicytes by TNF or IL-1 induces the release of HMG-1, which may participate in the regulation of neuroendocrine and immune responses to infection or injury.
Wang
H
H
Department of Emergency Medicine, North Shore University Hospital-New York University School of Medicine, USA.
Vishnubhakat
J M
JM
Bloom
O
O
Zhang
M
M
Ombrellino
M
M
Sama
A
A
Tracey
K J
KJ
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D024243:HMGB1 Protein; D006609:High Mobility Group Proteins / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002352:Carrier Proteins; D024243:HMGB1 Protein; D006609:High Mobility Group Proteins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma