Opposing effects of pituitary leukemia inhibitory factor and SOCS-3 on the ACTH axis response to inflammation

American Journal of Physiology. Endocrinology and Metabolism
Vera ChesnokovaShlomo Melmed

Abstract

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 counter...Continue Reading

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Citations

May 4, 2011·Stem Cell Reviews and Reports·Marie-Emmanuelle MathieuHélène Bœuf
Feb 19, 2004·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Robert N PechnickRussell E Poland
Feb 11, 2005·Laboratory Investigation; a Journal of Technical Methods and Pathology·Marietta A WeberBernhard Ryffel
Jun 30, 2005·American Journal of Physiology. Endocrinology and Metabolism·Anastasia KariaginaVera Chesnokova
Jun 14, 2020·International Journal of Molecular Sciences·Maciej WójcikAgata Krawczyńska
Sep 27, 2003·Endocrinology·Anastasia KariaginaVera Chesnokova
Jan 17, 2003·Stem Cells·Donald Metcalf

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