Interleukin-12 p40 Gene Expression Is Induced in Lipopolysaccharide-Activated Pituitary Glands in vivo

Yang, Young; Han, Seung Hyun; Kim, Hyun; Kim, Changmee; Kim, Kun Yong; Shin, Sun Mi; Choi, Inpyo; Pyun, Kwang Ho

doi:10.1159/000059431

Cited by 4 publications

(4 citation statements)

References 41 publications

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“…It is produced mainly by monocytes and macrophages and is a crucial factor in directing the T-cell response to infection, by inducing a Th1-type cytokine response. Our data agrees with that of previous reports showing that IL-12p40 is strongly up-regulated in-vitro (in response to an inflammatory stimulus) and in-vivo in the cerebral cortex of TgAPPsw mice [12,37,38]. …”

Section: Discussionsupporting

confidence: 93%

Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease

Patel

Paris

Mathura

et al. 2005

J Neuroinflammation

272

116

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BackgroundInflammation is believed to play an important role in the pathology of Alzheimer's disease (AD) and cytokine production is a key pathologic event in the progression of inflammatory cascades. The current study characterizes the cytokine expression profile in the brain of two transgenic mouse models of AD (TgAPPsw and PS1/APPsw) and explores the correlations between cytokine production and the level of soluble and insoluble forms of Aβ.MethodsOrganotypic brain slice cultures from 15-month-old mice (TgAPPsw, PS1/APPsw and control littermates) were established and multiple cytokine levels were analyzed using the Bio-plex multiple cytokine assay system. Soluble and insoluble forms of Aβ were quantified and Aβ-cytokine relationships were analyzed.ResultsCompared to control littermates, transgenic mice showed a significant increase in the following pro-inflammatory cytokines: TNF-α, IL-6, IL-12p40, IL-1β, IL-1α and GM-CSF. TNF-α, IL-6, IL-1α and GM-CSF showed a sequential increase from control to TgAPPsw to PS1/APPsw suggesting that the amplitude of this cytokine response is dependent on brain Aβ levels, since PS1/APPsw mouse brains accumulate more Aβ than TgAPPsw mouse brains. Quantification of Aβ levels in the same slices showed a wide range of Aβ soluble:insoluble ratio values across TgAPPsw and PS1/APPsw brain slices. Aβ-cytokine correlations revealed significant relationships between Aβ1–40, 1–42 (both soluble and insoluble) and all the above cytokines that changed in the brain slices.ConclusionOur data confirm that the brains of transgenic APPsw and PS1/APPsw mice are under an active inflammatory stress, and that the levels of particular cytokines may be directly related to the amount of soluble and insoluble Aβ present in the brain suggesting that pathological accumulation of Aβ is a key driver of the neuroinflammatory response.

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Section: Discussionsupporting

confidence: 93%

Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease

Patel

Paris

Mathura

et al. 2005

J Neuroinflammation

272

116

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“…Our results show for the first time that both LPS and restraint stress cause marked increases in NF‐κB activity in the anterior pituitary gland. Although the former response was expected on the basis of in vitro data reported in the present study, as well as elsewhere (29), the latter was unexpected and raises the possibility that the role of the NF‐κB system in mediating the body’s response to stress extends beyond immunological challenge. The finding that PHA781353E reduced the LPS‐induced release of ACTH and abolished the pituitary‐adrenocortical response to restraint stress suggests that NF‐κB has an important role in mediating the pituitary response.…”

Section: Discussionsupporting

confidence: 75%

Evidence From In Vitro and In Vivo Studies Showing that Nuclear Factor‐Kappa B Within the Pituitary Folliculostellate Cells and Corticotrophs Regulates Adrenocorticotrophic Hormone Secretion in Experimental Endotoxaemia

Mehet

Philip

Solito

et al. 2012

J Neuroendocrinology

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The hypothalamic-pituitary-adrenocortical (HPA) responses to bacterial infection are mediated, in part, by the actions of lipopolysaccharide (LPS) on pituitary folliculostellate (FS) cells that release pro-inflammatory cytokines [e.g. interleukin (IL)-6] and thereby facilitate adrenocorticotrophic hormone (ACTH) release from neighbouring corticotrophs. In the present study, two murine pituitary cell lines [TtT/GF (FS cells) and AtT20 D16:16 (corticotrophs)], alone and in co-culture, and an in vivo model of endotoxaemia were used to examine the potential role of nuclear factor-kappa B (NF-κB) in mediating LPS-induced ACTH secretion. Both cell lines expressed mRNAs for the key components of the LPS signalling system. LPS stimulated IL-6 release from TtT/GF cells via a glucocorticoid-sensitive, NF-κB-dependent mechanism; it also activated NF-κB in AtT20 cells, as did corticotrophin-releasing hormone (CRH). IL-6 potentiated (but LPS reduced) the stimulatory effects of CRH on ACTH release from AtT20 cells, whereas blockade of NF-κB (SC-514) increased the ACTH release induced by CRH in the presence or absence of LPS. In co-cultures, CRH and LPS acted synergistically to induce release of both IL-6 and ACTH. However, although SC-514 suppressed the release of IL-6 evoked by CRH and LPS, it potentiated the concomitant increase in ACTH release. In vivo both immunological (LPS) and psychological (restraint) stress increased intrapituitary NF-κB, whereas an NF-κB inhibitor (PHA781535E) attenuated the LPS-induced release of ACTH and abolished the HPA response to restraint stress. The results obtained in the present study support the premise that NF-κB plays an important role in mediating LPS signalling in the anterior pituitary gland, particularly in relation to IL-6 and ACTH secretion, and provide novel evidence that NF-κB blockade in vivo compromises stress-induced ACTH release.

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“…The corticosterone response in IL-12treated, LCMV-infected mice was shown to be largely dependent on TNF (223). In addition, IL-12 mRNA has been detected in the brains (microglia) of LPS-treated mice (229), in the pituitary glands of LPS-treated rats (340), and in the adrenal glands of mice undergoing graftversus-host disease (GVHD) (341).…”

Section: Interleukin-12mentioning

confidence: 99%

Immune Modulation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis during Viral Infection

et al. 2005

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Compelling data has been amassed indicating that soluble factors, or cytokines, emanating from the immune system can have profound effects on the neuroendocrine system, in particular the hypothalamic- pituitary-adrenal (HPA) axis. HPA activation by cytokines (via the release of glucocorticoids), in turn, has been found to play a critical role in restraining and shaping immune responses. Thus, cytokine-HPA interactions represent a fundamental consideration regarding the maintenance of homeostasis and the development of disease during viral infection. Although reviews exist that focus on the bi-directional communication between the immune system and the HPA axis during viral infection (188,235), others have focused on the immunomodulatory effects of glucocorticoids during viral infection (14,225). This review, however, concentrates on the other side of the bi-directional loop of neuroendocrine-immune interactions, namely, the characterization of HPA axis activity during viral infection and the mechanisms employed by cytokines to stimulate glucocorticoid release.

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Interleukin-12 p40 Gene Expression Is Induced in Lipopolysaccharide-Activated Pituitary Glands in vivo

Cited by 4 publications

References 41 publications

Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease

Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease

Evidence From In Vitro and In Vivo Studies Showing that Nuclear Factor‐Kappa B Within the Pituitary Folliculostellate Cells and Corticotrophs Regulates Adrenocorticotrophic Hormone Secretion in Experimental Endotoxaemia

Immune Modulation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis during Viral Infection

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