Cytokines and the endocrine system. I. The immunoendocrine network

Mandrup‐Poulsen, Thomas; Nerup, Jørn; Reimers, Jørgen; Pociot, Flemming; Andersen, Henrik U; Karlsen, A. E.; Bjerre, Ulla; Bergholdt, Regine

doi:10.1530/eje.0.1330660

Cited by 67 publications

(23 citation statements)

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“…Several mechanisms may regulate the ␤-cell response to cytokines, including antagonists such as specific binding proteins and soluble receptors, other cytokines, growth factors, and hormones (26,27). In contrast, the SOCS system represents an intracellular, fast-acting, regulated, negative feedback system for cytokine signaling.…”

Section: Discussionmentioning

confidence: 99%

Suppressor of cytokine signaling 3 (SOCS-3) protects β-cells against interleukin-1β- and interferon-γ-mediated toxicity

Karlsen

Rønn

Lindberg

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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131

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Suppressor of cytokine signaling 3 (SOCS-3) is a negative feedback regulator of IFN-␥ signaling, shown up-regulated in mouse bone marrow cells by the proinflammatory cytokines interleukin-1␤ (IL-1␤), tumor necrosis factor-␣ (TNF-␣), and IFN-␥. IL-1␤ and IFN-␥ alone, or potentiated by TNF-␣, are cytotoxic to the insulin producing pancreatic ␤-cells and ␤-cell lines in vitro and suggested to contribute to the specific ␤-cell destruction in Type-1 diabetes mellitus (T1DM). Using a doxycycline-inducible SOCS-3 expression system in the rat ␤-cell line INS-1, we demonstrate that the toxic effect of both IL-1␤ or IFN-␥ at concentrations that reduced the viability by 50% over 3 days, was fully preventable when SOCS-3 expression was turned on in the cells. At cytokine concentrations or combinations more toxic to the cells, SOCS-3 overexpression yielded a partial protection. Whereas SOCS-3-mediated inhibition of IFN-␥ signaling is described in other cell systems, SOCS-3 mediated inhibition of IL-1␤ signaling has not previously been described. In addition we show that SOCS-3 prevention of IL-1␤-induced toxicity is accompanied by inhibited transcription of the inducible nitric oxide synthase (iNOS) by 80%, resulting in 60% decreased formation of the toxic nitric oxide (NO). Analysis of isolated native rat islets exposed to IL-1␤ revealed a naturally occurring but delayed up-regulated SOCS-3 transcription. Influencing SOCS-3 expression thus represents an approach for affecting cytokine-induced signal transduction at a proximal step in the signal cascade, potentially useful in future therapies aimed at reducing the destructive potential of ␤-cell cytotoxic cytokines in T1DM, as well as other cytokine-dependent diseases.

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Section: Discussionmentioning

confidence: 99%

Suppressor of cytokine signaling 3 (SOCS-3) protects β-cells against interleukin-1β- and interferon-γ-mediated toxicity

Karlsen

Rønn

Lindberg

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

131

100

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“…In the present study we evaluated possible cycle-associated changes in the proinflammatory cytokines (IL-6 and TNF-a) thought to modulate the expression of VCAM-1. It is known that both cytokines [1] exert pleiotropic effects on various sites across the reproductive system (50,(58)(59)(60)(61)(62); [2] are present in the follicular fluid (FF); and [3] pituitary hormones and gonadotropins can modulate their production and secretion (IL-6) (50,63,64).…”

Section: Figurementioning

confidence: 99%

Serum levels of soluble vascular cell adhesion molecule-1, tumor necrosis factor-α, and interleukin-6 in in vitro fertilization cycles

Souter

Huang

Martı́nez-Maza

et al. 2009

Fertility and Sterility

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“…Many so-called immunoregulatory cytokines show pleiotropic functions and are produced in a number of environmentally distinct organs or tissues (Dinarello 1988;Kishimoto 1989;Kluger 1991;Awatsuji et al 1993;Mandrup-Poulsen et al 1995). These observations suggest that immunoregulatory cytokines may have different physiological roles in different organs or tissues.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical and immuno-electron-microscopic detection of interferon-γ-inducing factor (”interleukin-18") in mouse intestinal epithelial cells

Takeuchi

Nishizaki

Sano

et al. 1997

Cell and Tissue Research

110

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The novel cytokine interferon-gamma-inducing factor ("interleukin-18") is produced by macrophage-like cells in mice with endotoxin shock and induces the production of interferon-gamma by T cells in vitro. To determine the physiological role for mouse interferon-gamma-inducing factor, we studied its tissue distribution in several organs (intestine, spleen, thymus, kidney, and liver) in healthy mice of different ages, including fetal stages. Activity of the cytokine in the organ extracts of adult mice was measured by enzyme-linked immunosorbent assay, and the cellular distribution of interferon-gamma-inducing factor in organs from fetal and adult mice was determined by immunohistochemistry. Intestinal extracts of adult mice showed the highest concentrations among the organs studied. Other organ extracts of adult mice showed lower concentrations of the cytokine. Immunohistochemical analysis revealed that interferon-gamma-inducing factor was localized in the cytoplasm of intestinal epithelial cells from fetal and adult mice. These results show for the first time that intestinal epithelial cells may be the main producers of interferon-gamma-inducing factor under normal physiological conditions and suggest that its constitutive expression in intestinal epithelial cells may have an important role in the induction of mucosal immunity.

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Cytokines and the endocrine system. I. The immunoendocrine network

Cited by 67 publications

References 0 publications

Suppressor of cytokine signaling 3 (SOCS-3) protects β-cells against interleukin-1β- and interferon-γ-mediated toxicity

Suppressor of cytokine signaling 3 (SOCS-3) protects β-cells against interleukin-1β- and interferon-γ-mediated toxicity

Serum levels of soluble vascular cell adhesion molecule-1, tumor necrosis factor-α, and interleukin-6 in in vitro fertilization cycles

Immunohistochemical and immuno-electron-microscopic detection of interferon-γ-inducing factor (”interleukin-18") in mouse intestinal epithelial cells

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