Interleukin-12 p40 gene expression is induced in lipopolysaccharide-activated pituitary glands in vivo.
Proinflammatory cytokines have several functions including activation of the hypothalamo-pituitary-adrenal (HPA) axis and regulation of the immune system. The present study focuses on the regulation of interleukin 12 (IL-12) and its receptor gene expression in the HPA axis under artificially induced immune stress, brought on by administration of lipopolysaccharide (LPS) to Sprague-Dawley (SD) rats. RT-PCR analyses showed that expression of the IL-12 p40 gene was significantly increased and peaked at 2 h in the pituitary gland, but not in the hypothalamus. LPS-induced IL-12 p40 gene induction in the pituitary gland was suppressed after beta-adrenoceptor agonist pretreatment in vivo. Both IL-12 p40 gene induction and IL-12 production were also observed when freshly isolated pituitary glands from non-treated SD rats were incubated with LPS in vitro. Furthermore, CD14, which is known as a LPS receptor, was found to be expressed in the pituitary gland. Gel mobility shift assays using nuclear extracts prepared from the pituitary glands of rats administered LPS showed induction of NF-kappaB and AP-1 DNA-binding activity. These results suggest that LPS stimulates the pituitary gland directly in vivo to increase IL-12 p40 gene expression and IL-12 protein production.
Yang
Young
Y
Laboratory of Immunology, Korea Research Institute of Bioscience and Biotechnology, Korea University College of Medicine, Seoul, South Korea.
Han
Seung Hyun
SH
Kim
Hyun
H
Kim
Changmee
C
Kim
Kun-yong
KY
Shin
Sun Mi
SM
Choi
Inpyo
I
Pyun
Kwang Ho
KH
D000818:Animals; D015152:Blotting, Northern; D004247:DNA / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D017403:In Situ Hybridization; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics*; D053762:Interleukin-12 Subunit p40; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009924:Organ Culture Techniques; D010902:Pituitary Gland / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000737:chemistry; D021122:Protein Subunits; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism
D053762:Interleukin-12 Subunit p40; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D021122:Protein Subunits; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D018808:Transcription Factor AP-1; D018664:Interleukin-12; D004247:DNA