Effect of interleukin-6 receptor blockage on renal injury in apolipoprotein E-deficient mice

Tomiyama-Hanayama, Mari; Rakugi, Hiromi; Kohara, Masaharu; Mima, Toru; Adachi, Yasuo; Ohishi, Mitsuru; Katsuya, Tomohiro; Hoshida, Yoshihiko; Aozasa, Katsuyuki; Ogihara, Toshio; Nishimoto, Norihiro

doi:10.1152/ajprenal.90680.2008

Cited by 41 publications

(30 citation statements)

References 31 publications

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“…The specific blockade of IL-6 signaling with MR16-1 has been well confirmed in previous studies (Tamura et al 1993;Takagi et al 1998;Katsume et al 2002;Tomiyama-Hanayama et al 2009). …”

Section: Introductionsupporting

confidence: 73%

Treatment with Anti-Interleukin-6 Receptor Antibody Ameliorates Intestinal Polyposis in ApcMin/+ Mice under High-Fat Diet Conditions

Yaoita

Sasaki

Yokozawa

et al. 2015

Tohoku J. Exp. Med.

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The prevalence of colorectal malignancies is increasing in the world. The parallel increase of metabolic syndrome gives a speculation between these two conditions, although the precise mechanism is still unclear. Interleukin-6 (IL-6) is a cytokine known to correlate with obesity and serve as a proinflammatory adipokine. In the present study, we investigated the effect of IL-6 signaling blockade on intestinal polyp formation in obesity using a mouse model of adenomatous polyposis coli (Apc). Male C57BL/6J-Apc Min/+ mice were fed a high-fat diet from 5 weeks of age, and the overweight mice thus obtained were given a weekly intraperitoneal injection of anti-mouse IL-6 receptor antibody (MR16-1) from 6 to 15 weeks of age, while control mice received IgG or phosphate-buffered saline (PBS). The total number of intestinal polyps was significantly decreased in the MR16-1-injected group (53.1 ± 6.8) relative to the control groups (PBS-injected, 81.3 ± 6.1; rat IgG-injected, 74.7 ± 4.8, p = 0.01), and in particular the number of polyps larger than 2 mm in diameter was markedly decreased. In addition, the mean diameter of polyps in the MR16-1-injected group was significantly smaller than that in the control groups. On the other hand, no significant differences in body weight, epididymal fat pad mass, or the plasma levels of glucose, insulin and triglyceride were observed among the three groups. Thus, treatment with anti-IL-6 receptor antibody suppressed polyp growth in obese Apc Min/+ mice fed the high-fat diet. We suggest that IL-6 signaling may be responsible for the obesity-associated colorectal tumorigenesis.

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“…The specific blockade of IL-6 signaling with MR16-1 has been well confirmed in previous studies (Tamura et al 1993;Takagi et al 1998;Katsume et al 2002;Tomiyama-Hanayama et al 2009). …”

Section: Introductionsupporting

confidence: 73%

Treatment with Anti-Interleukin-6 Receptor Antibody Ameliorates Intestinal Polyposis in ApcMin/+ Mice under High-Fat Diet Conditions

Yaoita

Sasaki

Yokozawa

et al. 2015

Tohoku J. Exp. Med.

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“…The specificity and blocking ability of this monoclonal antibody has been confirmed in previous reports. 48,49 Detection of antigen-specific CD8 + /IFN-c + T lymphocytes in lymph nodes Three days after the last DNA vaccination, pooled right and left inguinal lymph node cells were harvested from various DNA-transfected mice. Before intracellular IFN-g staining, 1Â10 6 pooled lymph node cells were incubated for 18 h with a peptide pool composed of 10 mg ml -1 each of peptide 362-370 (EFAGK-KI) (BioBasic, Canada) and peptide 404-412 (EEITGYLYI) (BioBasic, Markham, Canada) of the HER-2/neu sequence.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

RNA interference-mediated silencing of Foxo3 in antigen-presenting cells as a strategy for the enhancement of DNA vaccine potency

Chang

Yen

et al. 2010

Gene Ther

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The transcription factor Forkhead box O3 (Foxo3) has a critical role in suppressing the expansion of antigen-specific effector T-cell populations; hence, Foxo3 is a potential target for enhancing the antitumor immunity of cancer vaccines. In this report, we evaluated the potential of RNA interference (RNAi)-mediated silencing of Foxo3 in antigen-presenting cells as an adjuvant for HER2/neu DNA cancer vaccines. Bicistronic plasmids expressing the N-terminal extracellular domain of human HER-2/neu and the Foxo3 short hairpin RNA (hN'-neu-Foxo3 shRNA) or the scrambled control (hN'-neu-scramble shRNA) were subcutaneously injected into mice by gene gun administration to elicit antitumor immunity against p185neu-overexpressing MBT-2 bladder tumor cells. We found that mice treated with hN'-neu-Foxo3 shRNA showed greater reductions in tumor growth and longer survival times than mice treated with hN'-neu-scramble shRNA, indicating that the silencing of Foxo3 enhanced the antitumor efficacy of the HER-2/neu cancer vaccine. Cytotoxicity analyses further revealed that the Foxo3 shRNA-enhanced antitumor effect was associated with significant increases in the number of functional CD8 + T cells and in the levels of cytotoxic T lymphocytes activity. Interleukin-6 was induced by hN'-neu-Foxo3 shRNA treatment but did not have a critical role in the antitumor effect of the hN'-neu-Foxo3 shRNA vaccine. Moreover, in vivo lymphocyte depletion analyses confirmed that the antitumor efficacy of the hN'-neu-Foxo3 shRNA vaccine depended on functional CD8 + T cells. Finally, Foxo3 suppression was shown to markedly improve the effect of the HER-2/neu DNA vaccine in limiting the growth and lung metastases of MBT-2 cells. Overall, these results support RNAi-mediated silencing of Foxo3 as an effective strategy to enhance the therapeutic antitumor effect of HER-2/neu DNA vaccines against p185neu-positive tumors.

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“…IL-6 is a key inflammatory molecule in renal diseases. Treatment with anti-IL-6 receptor antibody MR16-1 prevents progression of proteinuria, renal lipid deposit, and the mesangial cell proliferation in hypercholesterolemia-induced renal injury (44). Inhibition of TNF-α by a TNF-α antagonist, decreased blood pressure and protect the kidney through reduction of renal NF-κB, oxidative stress, and inflammation (45).…”

Section: Anti-inflammatory Therapymentioning

confidence: 99%

Obesity-Related Glomerulopathy

Mohamed¹

2017

Electron J Gen Med

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Obesity is a major risk factor for renal disease and can cause de novo glomerulopathy. The characteristic finding of obesity-induced renal injury includes glomerular hypertrophy, glomerular basement membrane thickening, mesangial matrix expansion, and increased renal inflammation. These changes may lead to albuminuria, a progressive impairment of renal function, glomerulosclerosis and tubulointerstitial fibrosis. The mechanisms of obesity-related glomerulopathy (ORG) are not well understood however, several mechanisms acting singly or in combination have been suggested as excess excretory load, excess renal sodium retention and insulin resistance (IR) and hyperinsulinemia, increased monocyte chemoattractant protein 1 (MCP-1) expression, Lipotoxicity in proximal tubular cells, increased inflammatory cytokine production such as Interleukin (IL) IL-6, IL-1, and tumor necrosis factor (TNF-α). Activation of NFκB transcription, increase Leptin levels, reduction in plasma adiponectin expression with its anti-inflammatory effects, decrease nitric oxide (NO) level, increase reactive oxygen species (ROS) generation, Hyperlipidemia, and increases in plasma renin activity, angiotensinogen, angiotensin-converting enzyme activity, and circulating AngII. Many lines of treatment are suggested for ORG as Peroxisome proliferator-activated receptors (PPAR) Agonistic, Statins, anti-inflammatory therapy, and antioxidants are under trial. Weight loss decreases of proinflammatory factors, increase of anti-inflammatory molecules and reduces oxidative stress state in obesity, which may protect renal function. This review discusses recent data about ORG, the characteristics of pathogens and possible interventions to prevent kidney injury in obesity.

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Effect of interleukin-6 receptor blockage on renal injury in apolipoprotein E-deficient mice

Cited by 41 publications

References 31 publications

Treatment with Anti-Interleukin-6 Receptor Antibody Ameliorates Intestinal Polyposis in <i>Apc</i><sup><i>Min/+</i></sup> Mice under High-Fat Diet Conditions

Treatment with Anti-Interleukin-6 Receptor Antibody Ameliorates Intestinal Polyposis in <i>Apc</i><sup><i>Min/+</i></sup> Mice under High-Fat Diet Conditions

RNA interference-mediated silencing of Foxo3 in antigen-presenting cells as a strategy for the enhancement of DNA vaccine potency

Obesity-Related Glomerulopathy

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