Elevated IL-13Rα2 in intestinal epithelial cells from ulcerative colitis or colorectal cancer initiates MAPK pathway

Mandal, Debasmita; Levine, Alan D.

doi:10.1002/ibd.21133

Cited by 42 publications

(34 citation statements)

References 42 publications

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“…IL-13 is elevated in the ulcerative colitis mucosa and may induce deregulated signaling in neighboring intestinal epithelial cells; therefore, IL-13 may be considered a tumorigenic cytokine. In addition, IL-13Rα2 as a decoy receptor may also participate in modulating the balance and intensity of the signaling pathways initiated in ulcerative colitis and colorectal cancer (20). IL-13-associated pathways are also involved in the development of other tumors.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-13 and its receptors in colorectal cancer (Review)

Zhou

Shen

et al. 2013

Biomedical Reports

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Abstract. Interleukin (IL)-13 is an immunoregulatory cytokine secreted by numerous immune cells. Its functions are similar to those of IL-4 and they share a common receptor. This cytokine has been included in recent studies on human tumors and malignant diseases, evoking a scientific interest to investigate the role of IL-13 and its receptors as novel biomarkers and targets for therapy. Colorectal cancer is one of the most common human malignancies, its prognosis is not promising and the efficacy of molecular-targeted therapy has not been established. This review summarizes the currently available data on the role of IL-13 and its receptors in colorectal cancer, including the signaling pathways involved in mediating the effects of IL-13, the role of IL-13 and/or its receptors in the prediction of cancer and several drugs targeting IL-13 or its receptors that are currently under evaluation.

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Section: Introductionmentioning

confidence: 99%

Interleukin-13 and its receptors in colorectal cancer (Review)

Zhou

Shen

et al. 2013

Biomedical Reports

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“…IL-13Ra2 can be induced by STAT6-dependent as well as STAT6-independent signals (22) and is expressed at elevated levels in fibrotic tissue. Reports have suggested that IL-13Ra2 can transduce STAT6-independent signals that may contribute to fibrosis (23)(24)(25), although these studies relied on ectopic IL-13Ra2 overexpression in cell lines. IL-13Ra2 has a short 17-aa cytoplasmic tail that contains no known canonical signaling motifs, and it has not been shown to form complexes with any other cell surface proteins capable of signaling.…”

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confidence: 99%

Endogenously Expressed IL-13Rα2 Attenuates IL-13–Mediated Responses but Does Not Activate Signaling in Human Lung Fibroblasts

Chandriani¹,

DePianto²,

N'Diaye³

et al. 2014

The Journal of Immunology

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IL-13 can bind to two distinct receptors: a heterodimer of IL-13Rα1/IL-4Rα and IL-13Rα2. Whereas IL-13Rα1/IL-4Rα engagement by IL-13 leads to the activation of STAT6, the molecular events triggered by IL-13 binding to IL-13Rα2 remain incompletely understood. IL-4 can bind to and signal through the IL-13Rα1/IL-4Rα complex but does not interact with IL-13Rα2. Idiopathic pulmonary fibrosis is a progressive and generally fatal parenchymal lung disease of unknown etiology with no current pharmacologic treatment options that substantially prolong survival. Preclinical models of fibrotic diseases have implicated IL-13 activity on multiple cell types, including macrophages and fibroblasts, in initiating and perpetuating pathological fibrosis. In this study, we show that IL-13, IL-4, IL-13Rα2, and IL-13–inducible target genes are expressed at significantly elevated levels in lung tissue from patients with idiopathic pulmonary fibrosis compared with control lung tissue. IL-4 and IL-13 induce virtually identical transcriptional responses in human monocytes, macrophages, and lung fibroblasts. IL-13Rα2 expression can be induced in lung fibroblasts by IL-4 or IL-13 via a STAT6-dependent mechanism, or by TNF-α via a STAT6-independent mechanism. Endogenously expressed IL-13Rα2 decreases, but does not abolish, sensitivity of lung fibroblasts to IL-13 and does not affect sensitivity to IL-4. Genome-wide transcriptional analyses of lung fibroblasts stimulated with IL-13 in the presence of Abs that selectively block interactions of IL-13 with IL-13Rα1/IL-4Rα or IL-13Rα2 show that endogenously expressed IL-13Rα2 does not activate any unique IL-13–mediated gene expression patterns, confirming its role as a decoy receptor for IL-13 signaling.

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“…Research also shows the elevated level of both IL-13 and its receptors (IL-13Ralpha1 and IL-13Ralpha2) in colon mucosa and colon cancer cells (Mandal and Levine, 2010). IL-13 also appeared to be an activator of the STAT6 pathway (Mandal and Levine, 2010).…”

Section: Discussionmentioning

confidence: 96%

ThelL-8andIL-13Gene Polymorphisms in Inflammatory Bowel Disease and Colorectal Cancer

Walczak

Przybyłowska

Dziki

et al. 2012

DNA and Cell Biology

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Inflammatory bowel diseases (IBD) and colorectal cancer (CRC) are disorders that originate from immune disturbances. In our study, we evaluated the association between the -251 T/A interleukin (IL)-8 and the -1112 C/T IL-13 polymorphisms, the risk of IBD, and CRC development. Genotypes were determined by PCRrestriction fragment length polymorphism in 191 patients with CRC, 150 subjects with IBD, and 205 healthy controls. We found an association between CRC and the presence of the -251 TA genotype and A allele of the IL-8 gene (odds ratios [ORs] 2.28 and 1.65). A similar relationship was observed between these polymorphic variants and ulcerative colitis (OR 2.05 for the -251 TA genotype and OR 1.47 for the -251 A allele) as well as Crohn's disease (ORs 3.11 and 1.56, respectively). Our research also revealed that the CT and TT genotypes of the IL-13 -1112 C/T polymorphism may be connected with a higher risk of CRC (ORs 2.28 and 1.65). The same genotypes affected the susceptibility of IBD (ORs 2.26 and 3.72). Our data showed that the IL-8 -251 T/A and IL-13 -1112 C/T polymorphisms might be associated with the IBD and CRC occurrence and might be used as predictive factors of these diseases in a Polish population.

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Elevated IL-13Rα2 in intestinal epithelial cells from ulcerative colitis or colorectal cancer initiates MAPK pathway

Cited by 42 publications

References 42 publications

Interleukin-13 and its receptors in colorectal cancer (Review)

Interleukin-13 and its receptors in colorectal cancer (Review)

Endogenously Expressed IL-13Rα2 Attenuates IL-13–Mediated Responses but Does Not Activate Signaling in Human Lung Fibroblasts

ThelL-8andIL-13Gene Polymorphisms in Inflammatory Bowel Disease and Colorectal Cancer

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