Socs3

White, Christine; Nicola, Nicos A.

doi:10.4161/jkst.25045

Cited by 39 publications

(31 citation statements)

References 120 publications

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“…SOCS3 is thought to play an important role in determining T cell responses34. The data presented in this manuscript are consistent with an elevation of SOCS3 in DCs which limits the tolerogenic effect of DCs thus inducing T effector cells2035.…”

Section: Discussionsupporting

confidence: 85%

Role of Tyk-2 in Th9 and Th17 cells in allergic asthma

Übel

Graser

Koch

et al. 2014

Sci Rep

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In a murine model of allergic asthma, we found that Tyk-2(−/−) asthmatic mice have induced peribronchial collagen deposition, mucosal type mast cells in the lung, IRF4 and hyperproliferative lung Th2 CD4+ effector T cells over-expressing IL-3, IL-4, IL-5, IL-10 and IL-13. We also observed increased Th9 cells expressing IL-9 and IL-10 as well as T helper cells expressing IL-6, IL-10 and IL-21 with a defect in IL-17A and IL-17F production. This T helper phenotype was accompanied by increased SOCS3 in the lung of Tyk-2 deficient asthmatic mice. Finally, in vivo treatment with rIL-17A inhibited local CD4+CD25+Foxp3+ T regulatory cells as well as Th2 cytokines without affecting IL-9 in the lung. These results suggest a role of Tyk-2 in different subsets of T helper cells mediated by SOCS3 regulation that is relevant for the treatment of asthma, cancer and autoimmune diseases.

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Section: Discussionsupporting

confidence: 85%

Role of Tyk-2 in Th9 and Th17 cells in allergic asthma

Übel

Graser

Koch

et al. 2014

Sci Rep

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“…Similarly, while amylin stimulated VMH microglial IL-6 expression, it also had a negative feedback effect ( 44 ) on the expression of the gp130 component of the IL-6 receptor complex ( 45 ). In fact, the gp130 family of receptors can be activated by other cytokines such as LIF ( 39 , 46 ), although in our case amylin altered LIF expression only in cultured hypothalamic astrocytes, and this was an inhibitory rather than a stimulatory effect.…”

Section: Discussioncontrasting

confidence: 55%

Amylin-Induced Central IL-6 Production Enhances Ventromedial Hypothalamic Leptin Signaling

et al. 2014

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Amylin acts acutely via the area postrema to reduce food intake and body weight, but it also interacts with leptin over longer periods of time, possibly via the ventromedial hypothalamus (VMH), to increase leptin signaling and phosphorylation of STAT3. We postulated that amylin enhances VMH leptin signaling by inducing interleukin (IL)-6, which then interacts with its gp130 receptor to activate STAT3 signaling and gene transcription downstream of the leptin receptor. We found that components of the amylin receptor (RAMPs1–3, CTR1a,b) are expressed in cultured VMH astrocytes, neurons, and microglia, as well as in micropunches of arcuate and ventromedial hypothalamic nuclei (VMN). Amylin exposure for 5 days increased IL-6 mRNA expression in VMH explants and microglia by two- to threefold, respectively, as well as protein abundance in culture supernatants by five- and twofold, respectively. Amylin had no similar effects on cultured astrocytes or neurons. In rats, 5 days of amylin treatment decreased body weight gain and/or food intake and increased IL-6 mRNA expression in the VMN. Similar 5-day amylin treatment increased VMN leptin-induced phosphorylation of STAT3 expression in wild-type mice and rats infused with lateral ventricular IgG but not in IL-6 knockout mice or rats infused with ventricular IL-6 antibody. Lateral ventricular infusion of IL-6 antibody also prevented the amylin-induced decrease of body weight gain. These results show that amylin-induced VMH microglial IL-6 production is the likely mechanism by which amylin treatment interacts with VMH leptin signaling to increase its effect on weight loss.

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“…Additionally, SOCS2-ko ventricular myocytes showed no detectable mRNA expression of SOCS2, as expected. On the other hand, in LIF-treated myocytes there was a significant increase in the amount of SOCS3 associated with gp130, corroborating previous findings (23). Thus, in SOCS2-ko cells, SOCS3 is the predominant SOCS protein (Fig.…”

Section: Lif-induced Increase In Intracellular [Ca 2ϩ ] Transient Is supporting

confidence: 90%

Absence of suppressor of cytokine signaling 2 turns cardiomyocytes unresponsive to LIF-dependent increases in Ca²⁺ levels

Rocha‐Resende

Jesus

Roman‐Campos

et al. 2017

American Journal of Physiology-Cell Physiology

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Little is known regarding the role of suppressor of cytokine signaling (SOCS) in the control of cytokine signaling in cardiomyocytes. We investigated the consequences of SOCS2 ablation for leukemia inhibitory factor (LIF)-induced enhancement of intracellular Ca ([Ca]) transient by performing experiments with cardiomyocytes from SOCS2-knockout (ko) mice. Similar levels of SOCS3 transcripts were seen in cardiomyocytes from wild-type and SOCS2-ko mice, while SOCS1 mRNA was reduced in SOCS2-ko. Immunoprecipitation experiments showed increased SOCS3 association with gp130 receptor in SOCS2-ko myocytes. Measurements of Ca in wild-type myocytes exposed to LIF showed a significant increase in the magnitude of the Ca transient. This change was absent in LIF-treated SOCS2-ko cells. LIF activation of ERK and STAT3 was observed in both wild-type and SOCS2-ko cells, indicating that in SOCS2-ko, LIF receptors were functional, despite the lack of effect in the Ca transient. In wild-type cells, LIF-induced increase in [Ca] and phospholamban Thr17 [PLN(Thr17)] phosphorylation was inhibited by KN-93, indicating a role for CaMKII in LIF-induced Ca raise. LIF-induced phosphorylation of PLN(Thr17) was abrogated in SOCS2-ko myocytes. In wild-type cardiomyocytes, LIF treatment increased L-type Ca current (), a key activator of CaMKII in response to LIF. Conversely, SOCS2-ko myocytes failed to activate in response to LIF, providing a rationale for the lack of LIF effect on Ca transient. Our data show that absence of SOCS2 turns cardiomyocytes unresponsive to LIF-induced [Ca] raise, indicating that endogenous levels of SOCS2 are crucial for full activation of LIF signaling in the heart.

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Socs3

Cited by 39 publications

References 120 publications

Role of Tyk-2 in Th9 and Th17 cells in allergic asthma

Role of Tyk-2 in Th9 and Th17 cells in allergic asthma

Amylin-Induced Central IL-6 Production Enhances Ventromedial Hypothalamic Leptin Signaling

Absence of suppressor of cytokine signaling 2 turns cardiomyocytes unresponsive to LIF-dependent increases in Ca²⁺ levels

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Socs3

Cited by 39 publications

References 120 publications

Role of Tyk-2 in Th9 and Th17 cells in allergic asthma

Role of Tyk-2 in Th9 and Th17 cells in allergic asthma

Amylin-Induced Central IL-6 Production Enhances Ventromedial Hypothalamic Leptin Signaling

Absence of suppressor of cytokine signaling 2 turns cardiomyocytes unresponsive to LIF-dependent increases in Ca2+ levels

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Absence of suppressor of cytokine signaling 2 turns cardiomyocytes unresponsive to LIF-dependent increases in Ca²⁺ levels