Interleukin-6 Signaling in Liver-Parenchymal Cells Suppresses Hepatic Inflammation and Improves Systemic Insulin Action

Wunderlich, Frank; Ströhle, Peter; Könner, A. Christine; Gruber, Sabine; Tovar, Sulay; Brönneke, Hella S.; Juntti‐Berggren, Lisa; Li, Luo Sheng; Rooijen, Nico van; Libert, Claude; Berggren, Per Olof; Brüning, Jens C.

doi:10.1016/j.cmet.2010.06.011

Cited by 200 publications

(165 citation statements)

References 48 publications

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“…1E). Moreover, we also created IL-6Ra deficiency specifically in liver parenchymal cells (IL-6Ra L-KO mice) (17) and in the myeloid lineage (IL-6Ra…”

Section: Resultsmentioning

confidence: 99%

“…To generate IL-6Ra-deficient (knockout; KO) mice (IL-6Ra KO mice), IL-6Ra floxed mice were crossed with deleter-cre mice, and offspring were intercrossed. IL-6Ra deficiency in liver parenchymal cells (IL-6Ra L-KO mice) was generated, as described previously (17). Myeloid lineage-specific IL-6Ra-deficient mice (IL-6Ra…”

Section: Generation Of Il-6ra-deficient Micementioning

confidence: 99%

“…Generation of IL-6Ra floxed mice was done, as described previously (17). Briefly, we flanked exons 2 and 3 of the IL-6Ra gene by loxP sites using standard gene-targeting techniques in C57/BL-6-derived embryonic stem cells.…”

Section: Generation Of Il-6ra-deficient Micementioning

confidence: 99%

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Cutting Edge: Inhibition of IL-6 Trans-Signaling Protects from Malaria-Induced Lethality in Mice

Wunderlich

Delić

Behnke

et al. 2012

The Journal of Immunology

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Circulating IL-6 levels correlate with the severity of blood-stage malaria in humans and mouse models, but the impact of IL-6 classic signaling through membrane IL-6Rα, as well as IL-6 trans-signaling through soluble IL-6Rα, on the outcome of malaria has remained unknown. In this study, we created IL-6Rα–deficient mice that exhibit a 50% survival of otherwise lethal blood-stage malaria of the genus Plasmodium chabaudi. Inducing IL-6 trans-signaling by injection of mouse recombinant soluble IL-6Rα in IL-6Rα–deficient mice restores the lethal outcome to malaria infection. In contrast, inhibition of IL-6 trans-signaling via injection of recombinant sGP130Fc protein in control mice results in a 40% survival rate. Our data demonstrate that IL-6 trans-signaling, rather than classic IL-6 signaling, contributes to malaria-induced lethality in mice, preceded by an increased inflammatory response. Therefore, inhibition of IL-6 trans-signaling may serve as a novel promising therapeutic basis to combat malaria.

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“…1E). Moreover, we also created IL-6Ra deficiency specifically in liver parenchymal cells (IL-6Ra L-KO mice) (17) and in the myeloid lineage (IL-6Ra…”

Section: Resultsmentioning

confidence: 99%

Section: Generation Of Il-6ra-deficient Micementioning

confidence: 99%

See 1 more Smart Citation

Cutting Edge: Inhibition of IL-6 Trans-Signaling Protects from Malaria-Induced Lethality in Mice

Wunderlich

Delić

Behnke

et al. 2012

The Journal of Immunology

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“…31) IL-6 can function as anti-inflammatory wherein it inhibits lipopolysaccharideinduced TNF-α and IL-1, 43) and downregulate inflammatory signaling cascades that regulate fatty acid oxidation in obese/ diabetic condition. 44) Besides, increased IL-6 secretion in obesity is associated in correcting excess body weight gain.…”

Section: Discussionmentioning

confidence: 99%

Anti-obesity Effect of Alkaline Reduced Water in High Fat-Fed Obese Mice

Ignacio

Kang

Kim

et al. 2013

Biological & Pharmaceutical Bulletin

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Whether or not alkaline reduced water (ARW) has a positive effect on obesity is unclear. This study aims to prove the positive effect of ARW in high-fat (HF) diet-induced obesity (DIO) in C57BL/6 mice model. Toward this, obesity was induced by feeding the C57BL/6 male mice with high-fat diet (w/w 45% fat) for 12 weeks. Thereafter, the animals were administered with either ARW or tap water. Next, the degree of adiposity and DIO-associated parameters were assessed: clinico-pathological parameters, biochemical measurements, histopathological analysis of liver, the expression of cholesterol metabolism-related genes in the liver, and serum levels of adipokine and cytokine. We found that ARW-fed mice significantly ameliorated adiposity: controlled body weight gain, reduced the accumulation of epididymal fats and decreased liver fats as compared to control mice. Accordingly, ARW coordinated the level of adiponectin and leptin. Further, mRNA expression of cytochrome P450 (CYP)7A1 was upregulated. In summary, our data shows that ARW intake inhibits the progression of HF-DIO in mice. This is the first note on anti-obesity effect of ARW, clinically implying the safer fluid remedy for obesity control.Key words alkaline reduced water; adiponectin; cytokine; adiposity; epididymal fat; cholesterol 7α-hydroxylase Obesity has reached global epidemic status. In developed and developing countries, obesity is reported to be the sixth most important risk factor contributing to the overall burden of chronic disease.1) Forty three million children, 82% of which from developing countries, are affected with obesity.2)The World Health Organization recently reported that there were more than 1 billion overweight adults worldwide, of whom 500 million were obese.3) Obesity poses a major public health issue as it is known to be positively associated with increased risk of certain chronic diseases such as cardiovascular disease, hypertension, type 2 diabetes and fatty liver. [3][4][5] Excessive intake of dietary fats influences the progression of obesity, 6) which is characterized by accumulation of body fats marked by abnormal increase in adipose tissue mass and liver fats (adiposity), dysregulated levels of adipokines, and imbalance between pro-and anti-inflammatory cytokine. 7-9)The complexity of these pathogenetic mechanisms of obesity poses a challenge to the development of effective therapy. In that context, there has been growing concern for the need of newer therapeutic strategies that directly deal with these mechanisms. Of several such candidates, we first introduced the alkaline reduced water (ARW) for obesity control in highfat (HF) diet-induced obesity (DIO) in mice model. ARW refers to electrolyzed water produced from minerals such as magnesium and calcium, which is characterized by supersaturated hydrogen, high pH, and a negative oxidation reduction potential. This hydrogen-rich functional water has been introduced as a feasible therapeutic strategy for health promotion and disease prevention. [10][11][12] Our previous studies ...

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“…In the same flow of thinking, IL-8 appears to have angiogenic effects 28,36,37 and IL-15, also produced by muscle contraction, seems to have anabolic effects and in the reduction of adiposity 36,37,86 . Although some studies do not show significant increases in the plasma IL-15 after exercise 87,88 , Tamura et al 89 observed this increase in individuals submitted to 30 minutes of exercise on a treadmill with an intensity of 70% of HRmax predicted by age (HRmax = 220 -age). The authors attribute the lack of consensus in the literature to the different experimental parameters and especially to the timing of the IL-15 measurement after exercise.…”

Section: Effect Of Physical Exercise In the Cytokine Productionmentioning

confidence: 99%

Efeito do exercício no sistema imune: resposta, adaptação e sinalização celular

Terra

Da-Silva

Salerno

et al. 2012

Rev Bras Med Esporte

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Introduction: Over the last century, people have become less active, adopting more sedentary habits. This scenario has increased the incidence of chronic diseases such as cardiovascular diseases, type 2 diabetes and metabolic syndrome. The practice of physical activities can influence healthiness by altering the metabolic state and also the immune system. Objective: To review the literature for studies that address the effects promoted by physical exercise on the development of immune responses and the possible signal transduction pathways. Methods: The SciELO and PubMed data bases were consulted. Results: The available literature shows that during the practice of exercise, various subpopulations of leukocytes are altered in accordance with the intensity and duration of the activity performed. Exercise of moderate intensity stimulates a pro-inflammatory response, while those of high intensity tend to promote antiinflammatory responses that could decrease damage to skeletal muscle. Such alterations are observed in cells that present antigens (such as macrophages and dendritic cells), neutrophils, natural killer cells (NK) and in surface molecules like Toll-like receptors (TLR) and major histocompatibility complex class II, as well as the entire repertoire of cytokines. Conclusion: The current state of knowledge suggests that the alterations in the immune system are dependent on parameters inherent to exercise and that in order to have all these alterations occurring, some cell signaling cascades are activated, giving rise to a complex process of phosphorylation/dephosphorylation that culminates in the activation of transcription factors, translation of mRNA's, protein synthesis and cell proliferation.

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Interleukin-6 Signaling in Liver-Parenchymal Cells Suppresses Hepatic Inflammation and Improves Systemic Insulin Action

Cited by 200 publications

References 48 publications

Cutting Edge: Inhibition of IL-6 Trans-Signaling Protects from Malaria-Induced Lethality in Mice

Cutting Edge: Inhibition of IL-6 Trans-Signaling Protects from Malaria-Induced Lethality in Mice

Anti-obesity Effect of Alkaline Reduced Water in High Fat-Fed Obese Mice

Efeito do exercício no sistema imune: resposta, adaptação e sinalização celular

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