Role of intracellular interleukin‐1 receptor antagonist in skin carcinogenesis

La, Eunhye; Rundhaug, Joyce E.; Fischer, Susan M.

doi:10.1002/mc.1031

Cited by 24 publications

(14 citation statements)

References 38 publications

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“…Interleukin-1 (IL-1) receptor antagonist, an anti-inflammatory protein secreted by adipose tissue (57), may be another adipokine with an anticarcinogenic effect (58,59). However, the role of IL-1/ IL-1 receptor/IL-1 receptor antagonist system in carcinogenesis has not been fully settled (60).…”

Section: Discussionmentioning

confidence: 99%

Susceptibility to Induced and Spontaneous Carcinogenesis Is Increased in Fatless A-ZIP/F-1 but not in Obese ob/ob Mice

Ablamunits

Cohen²,

Brazee³

et al. 2006

Cancer Research

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Obesity is typically associated with increased tumor susceptibility, whereas caloric restriction, a regimen resulting in leanness, inhibits carcinogenesis. The link between adiposity and malignancies suggests that adipose tissue may influence carcinogenesis. An adipose tissue hormone, leptin, could be procarcinogenic because it stimulates proliferation in various tissues and tumor cell lines. Leptin may contribute to the correlation between adiposity and malignancies as its levels are usually increased in obese subjects and reduced by caloric restriction. We hypothesized that leptin deficiency, despite obesity, would inhibit carcinogenesis in leptin-null ob/ob mice and tested this hypothesis in two models: (a) two-stage skin carcinogenesis initiated by 7,12-dimethylbenz(a)anthracene and promoted by phorbol 12-myristate 13-acetate (PMA) and (b) p53 deficiency. Contrary to a typical association between obesity and enhanced carcinogenesis, obese ob/ob mice developed induced skin papillomas and spontaneous p53-deficient malignancies, mostly lymphomas, similarly to their lean littermates. Surprisingly, lipodystrophic (ZIP) mice that had very little both adipose tissue and leptin were highly susceptible to carcinogenesis. Hyperphagia, hyperinsulinemia, and hyperglycemia are unlikely to have contributed significantly to the enhancement of carcinogenesis in ZIP mice because similarly hyperphagic, hyperinsulinemic, and hyperglycemic ob/ob mice had normal susceptibility to carcinogenesis. Our data suggest that, in contrast to a well-known correlation between obesity and cancer, the direct effect of adipose tissue may rather be protective. (Cancer Res 2006; 66(17): 8897-902)

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Section: Discussionmentioning

confidence: 99%

Susceptibility to Induced and Spontaneous Carcinogenesis Is Increased in Fatless A-ZIP/F-1 but not in Obese ob/ob Mice

Ablamunits

Cohen²,

Brazee³

et al. 2006

Cancer Research

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show abstract

“…Despite the lack of leader peptide, intracellular IL-1Ra isoforms can be released into the circulation by dying cells or actively secreted by an unknown leaderless pathway, and bind with high affinity to IL-1R1 to antagonize the effects of IL-1 [2]. In addition, intracellular IL-1R1-independent functions have also been reported for intracellular IL-1Ra isoforms [16][17][18][19].…”

Section: Il-1ramentioning

confidence: 94%

The interleukin (IL)-1 cytokine family – Balance between agonists and antagonists in inflammatory diseases

et al. 2015

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“…IL-1R blockade also reduced hepatic tumor growth [19]. Moreover, it has also been reported that IL-1Ra reduces fibrosarcoma development [20], B16 melanoma growth and metastasis [21], colon adenocarcinoma growth [22], and skin cancer development [23]. IL-1 knockout mice injected with melanoma failed to develop solid tumors [24].…”

Section: Introductionmentioning

confidence: 99%

Deficiency of C-C Chemokine Receptor 5 Suppresses Tumor Development via Inactivation of NF-κB and Upregulation of IL-1Ra in Melanoma Model

et al. 2012

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To evaluate the relevance of C-C chemokine receptor type 5 (CCR5) expression and tumor development, we compared melanoma growth in CCR5 knockout (CCR5−/−) mice and wild type (CCR5+/+) mice. CCR5−/− mice showed reduced tumor volume, tumor weight, and increased survival rate when compared to CCR5+/+ mice. We investigated the activation of NF-κB since it is an implicated transcription factor in the regulation of genes involving cell growth, apoptosis, and tumor growth. Significant inhibition of DNA binding activity of NF-κB, and translocation of p50 and p65 into the nucleus through the inhibition of phosphorylation of IκB was found in the melanoma tissues of CCR5−/− mice compared to melanoma tissues of CCR5+/+ mice. NF-κB target apoptotic protein expression, such as cleaved caspase-3, cleaved PARP, and Bax, was elevated, whereas the survival protein expression levels, such as Bcl-2, C-IAP1, was decreased in the melanoma tissues of CCR5−/− mice. Interestingly, we found that the level of IL-1Ra, a tumor growth suppressive cytokine, was significantly elevated in tumor tissue and spleen of CCR5−/− mice compared to the level in CCR5+/+ mice. Moreover, infiltration of CD8+ cytotoxic T cell and CD57+ natural killer cells was significantly increased in melanoma tumor and spleen tissue of CCR5−/− mice compared to that of CCR5+/+ mice. Therefore, these results showed that CCR5 deficiency caused apoptotic cell death of melanoma through inhibition of NF-κB and upregulation of IL-1Ra.

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Role of intracellular interleukin‐1 receptor antagonist in skin carcinogenesis

Cited by 24 publications

References 38 publications

Susceptibility to Induced and Spontaneous Carcinogenesis Is Increased in Fatless A-ZIP/F-1 but not in Obese ob/ob Mice

Susceptibility to Induced and Spontaneous Carcinogenesis Is Increased in Fatless A-ZIP/F-1 but not in Obese ob/ob Mice

The interleukin (IL)-1 cytokine family – Balance between agonists and antagonists in inflammatory diseases

Deficiency of C-C Chemokine Receptor 5 Suppresses Tumor Development via Inactivation of NF-κB and Upregulation of IL-1Ra in Melanoma Model

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