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rdf:type |
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lifeskim:mentions |
umls-concept:C0001655,
umls-concept:C0021368,
umls-concept:C0032005,
umls-concept:C0125606,
umls-concept:C0871261,
umls-concept:C1280500,
umls-concept:C1426212,
umls-concept:C1522496,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911692
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pubmed:issue |
5
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pubmed:dateCreated |
2002-4-5
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pubmed:abstractText |
We have shown that leukemia inhibitory factor (LIF) and suppressor of cytokine signaling (SOCS)-3 are expressed in the hypothalamus and pituitary and that LIF induces proopiomelanocortin (POMC) and ACTH, whereas SOCS-3 abrogates corticotroph POMC gene transcription and ACTH secretion. Here, we determined the role of pituitary LIF and SOCS-3 in regulating hypothalamo-pituitary-adrenal (HPA) axis inflammatory responses. Murine pituitary LIF expression was induced up to eightfold after intraperitoneal injection of lipopolysaccharide or tumor necrosis factor-alpha, concordant with elevated plasma levels of ACTH and corticosterone. In LIF knockout (LIFKO) mice, induction of both ACTH and corticosterone were attenuated. LIF deletion was associated with elevated (P < 0.05) levels of pituitary TNF-alpha, interleukin (IL)-1beta, and IL-6 mRNA and cytokine-inducible pituitary SOCS-3 expression. Abrogation of the HPA axis stress response and higher pituitary levels of proinflammatory cytokines observed in LIFKO mice resulted in a stronger inflammatory process, as evidenced by elevated erythrocyte sedimentation rate and increased serum amyloid A levels (P < 0.05). The results indicate that, although LIF induces ACTH, SOCS-3 acts to counterregulate the HPA axis response to inflammation.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenocorticotropic Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Corticosterone,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Leukemia Inhibitory Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Lif protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines,
http://linkedlifedata.com/resource/pubmed/chemical/Pro-Opiomelanocortin,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Socs3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0193-1849
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
E1110-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11934677-Acute Disease,
pubmed-meshheading:11934677-Adrenocorticotropic Hormone,
pubmed-meshheading:11934677-Animals,
pubmed-meshheading:11934677-Corticosterone,
pubmed-meshheading:11934677-Cytokines,
pubmed-meshheading:11934677-Female,
pubmed-meshheading:11934677-Gene Expression,
pubmed-meshheading:11934677-Growth Inhibitors,
pubmed-meshheading:11934677-Hypothalamo-Hypophyseal System,
pubmed-meshheading:11934677-Inflammation,
pubmed-meshheading:11934677-Interleukin-6,
pubmed-meshheading:11934677-Leukemia Inhibitory Factor,
pubmed-meshheading:11934677-Lipopolysaccharides,
pubmed-meshheading:11934677-Lymphokines,
pubmed-meshheading:11934677-Male,
pubmed-meshheading:11934677-Mice,
pubmed-meshheading:11934677-Mice, Knockout,
pubmed-meshheading:11934677-Neuroimmunomodulation,
pubmed-meshheading:11934677-Pituitary-Adrenal System,
pubmed-meshheading:11934677-Pro-Opiomelanocortin,
pubmed-meshheading:11934677-Proteins,
pubmed-meshheading:11934677-RNA, Messenger,
pubmed-meshheading:11934677-Repressor Proteins,
pubmed-meshheading:11934677-Suppressor of Cytokine Signaling Proteins,
pubmed-meshheading:11934677-Transcription Factors
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pubmed:year |
2002
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pubmed:articleTitle |
Opposing effects of pituitary leukemia inhibitory factor and SOCS-3 on the ACTH axis response to inflammation.
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pubmed:affiliation |
Cedars-Sinai Research Institute-University of California Los Angeles School of Medicine, Los Angeles, California 90048, USA. chesnokova@cshs.org
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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