IL-13 receptors and signaling pathways: An evolving web

Hershey, Gurjit K. Khurana

doi:10.1067/mai.2003.1333

Cited by 510 publications

(419 citation statements)

References 133 publications

Supporting

Mentioning

389

Contrasting

Unclassified

Order By: Relevance

“…As murine IL-13 can bind and signal through human IL-13Rs, it is possible that endogenous murine IL-13 provided such signals for metastasis. 29,30 It has been previously reported that IL-13 is produced by Th2 cells, Mast cells, B cells, NK cells and granulocytes. [31][32][33] Since immunodeficient mice used in our study lack Th2-polarized T-cells, which are main source of IL-13 production, the source of IL-13 in vivo is presumed to be from other host cells.…”

Section: Discussionmentioning

confidence: 99%

IL‐13 regulates cancer invasion and metastasis through IL‐13Rα2 via ERK/AP‐1 pathway in mouse model of human ovarian cancer

Fujisawa

Joshi

Puri

2011

Intl Journal of Cancer

127

112

View full text Add to dashboard Cite

Previously, we have demonstrated that a variety of human cancers including the ovarian cancer express IL-13Ra2, a high affinity receptor for IL-13. Herein, we have examined if IL-13 regulates invasion and metastasis of ovarian cancer through IL-13Ra2 in vitro and in vivo in animal models of human ovarian cancer. We tested cell invasion and protease activity in IL-13Ra2-overexpressing and IL-13Ra2-negative ovarian tumor cell lines. IL-13 treatment significantly augmented both cell invasion and enzyme activities in only IL-13Ra2-positive cells but not in IL-13Ra2-negative cells in vitro. Mechanistically, IL-13 enhanced ERK1/2, AP-1 and MMP activities only in IL-13Ra2-positive cells but not in IL-13Ra2-negative cells. In contrast, other signaling pathways such as IRS1/2, PI3K and AKT do not seem to be involved in IL-13 induced signaling in ovarian cancer cell lines. Highly specific inhibitors for MMP and AP-1 efficiently inhibited both invasion and protease activities without impacting the basal level invasion and protease activities in vitro. In orthotopic animal model of human ovarian cancer, IL-13Ra2-positive tumors metastasized to lymph nodes and peritoneum earlier than IL-13Ra2-negative tumors. Interestingly, the IL-13Ra2-positive tumor bearing mice died earlier than mice with IL-13Ra2-negative tumor. Intraperitoneal injection of IL-13 further shortened survival of IL-13Ra2-positive tumor bearing mice compared to IL-13Ra2-negative tumor mice. IL-13Ra2-positive tumors and lymph node metastasis expressed higher levels of MMPs and higher ERK1/2 activation compared to IL-13Ra2-negative tumors. Taken together, IL-13Ra2 is involved in cancer metastasis through activation of ERK/AP-1 and that targeting IL-13Ra2 might not only directly kill primary tumors but also prevent cancer metastasis.Ovarian cancer is the fifth major cause of cancer related deaths in women. It is estimated that 21,880 women will be diagnosed and 13,850 will die of ovarian cancer in 2010. 1 Severity of the disease is determined by staging, which is based on the distance and extent of cancer spread within the pelvic and peritoneal cavity. The 5-year survival rate of ovarian cancer patients is related to the stage of the disease. 2 Therefore, novel and effective anticancer therapies are needed to prevent cancer cell spread. We have previously reported that IL13Ra2 is a biomarker of disease in ovarian cancer and targeting of this receptor with specific immunotoxin decreases tumor burden and extends survival of animals. 3 Despite its overexpression in a variety of human tumors and its characterization as a potent target for receptor directed anticancer therapy, 4-7 the biology of this receptor is highly complex and not understood completely. IL-13Ra2 is one of two receptor subunits of IL-13R complex. Another key-player of the receptor complex is IL-13Ra1, which forms a productive complex with IL-4Ra upon binding to IL-13 and mediates signal transduction. On the other hand, IL13Ra2 does not seem to require IL-4Ra and by itself binds IL-13 with high af...

show abstract

Section: Discussionmentioning

confidence: 99%

IL‐13 regulates cancer invasion and metastasis through IL‐13Rα2 via ERK/AP‐1 pathway in mouse model of human ovarian cancer

Fujisawa

Joshi

Puri

2011

Intl Journal of Cancer

127

112

View full text Add to dashboard Cite

show abstract

“…Th2-related cytokines include IL-4, IL-5, IL-13, and Th17-related cytokines (tumor necrosis factor-alpha (TNF-α) IL-6, and IL-1β) [7]. IL-4 modulates IgE levels, resulting in inflammatory cell migration to inter-respiratory cells [8], and IL-13 induces morphological changes in the pulmonary system typical of asthma, such as mucous hypersecretion, epithelial hyperplasia, base membrane thickening, inflammatory cell infiltration, and B cell activation [9–12]. TNF-α is produced by macrophages and is involved in the interaction between mast cells [13] and airway smooth muscle cells, a key mechanism for inducing airway hyperresponsiveness [14].…”

Section: Introductionmentioning

confidence: 99%

Opuntia humifusamodulates morphological changes characteristic of asthma via IL-4 and IL-13 in an asthma murine model

Lee

Bae

Choi

et al. 2017

Food & Nutrition Research

View full text Add to dashboard Cite

Asthma is a chronic pulmonary disease that affects an estimated 235 million people worldwide, but asthma drugs have many adverse effects. Opuntia humifusa (eastern prickly pear) has been used as a food and traditional medicine worldwide; however, its anti-asthmatic effects have not been reported. We evaluated O. humifusa as a potential therapeutic or preventive component of anti-asthmatic drugs. We divided ovalbumin-sensitized mice into the following groups: normal control, asthma-induced control, dexamethasone-treated group (positive control), 50 mg/kg O. humifusa-treated group, 100 mg/kg O. humifusa-treated group, and 500 mg/kg O. humifusa-treated group. Levels of Th1/Th2/Th17-related cytokines were evaluated using RT-PCR, ELISA, and immunohistochemistry. O. humifusa dose-dependently suppressed the morphological changes typically observed in asthma, such as goblet cell hyperplasia, inflammatory cell infiltration, mucous hypersecretion, and relative basement membrane thickening in the respiratory system. These results may be attributable to regulation of Th1-/Th2-/Th17-related factors, especially interleukin (IL)-4 and IL-13. We conclude that O. humifusa is a potential anti-asthmatic functional food. Abbreviations: O. humifusa: Opuntia humifusa; Th: helper T; RT-PCR: real-time polymerase chain reaction; ELISA: enzyme-linked immunosorbent assay; IL: interleukin; WHO: World Health Organization; IFN-γ: interferon gamma; TNF-α: tumor necrosis factor-alpha; IgE: immunoglobulin E; CD: cluster of differentiation; OVA: ovalbumin; DEX: dexamethasone; BALF: bronchoalveolar fluid; H&E: hematoxylin and eosin; PAS: periodic acid-schiff; PBS: phosphate-buffered saline; BM: basement membrane; cDNA: complementary deoxyribonucleic acid; RNA: ribo nucleic acid; RIPA: radioimmunoprecipitation assay; IHC: immunohistochemistry; HPLC: high-performance liquid chromatography; SD: standard deviation; WBC: white blood cells; APCs: antigen-presenting cells

show abstract

“…A llergic immunopathology and host protection against helminth parasites are both mediated, in large part, by the type 2 cytokines IL-4, IL-5, IL-9, and IL-13 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Of these, a particularly prominent role is played by two related cytokines, IL-4 and IL-13.…”

mentioning

confidence: 99%

“…In contrast, the type 2 IL-4R, which is composed of the IL-4R␣ and IL-13R␣1 polypeptides (15,29,31,32), is expressed by some bone marrow-derived cells, including macrophages, as well as most non-bone marrow-derived cells and is activated by both IL-4 and IL-13 (28,29,33,34). Signaling through this receptor appears to be responsible for many proallergic effects of IL-4 and most proallergic effects of IL-13 (7,10,20,28,(33)(34)(35), although IL-13 signaling through a cell membrane form of an additional IL-13-binding protein, cell membrane IL-13R␣2, may contribute to the profibrotic effects of this cytokine (36).…”

mentioning

confidence: 99%

Differences in Expression, Affinity, and Function of Soluble (s)IL-4Rα and sIL-13Rα2 Suggest Opposite Effects on Allergic Responses

Khodoun

Lewis²,

Yang

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

IL-4 and IL-13 are each bound by soluble receptors (sRs) that block their activity. Both of these sRs (sIL-4Rα and sIL-13Rα2) are present in low nanogram per milliliter concentrations in the serum from unstimulated mice, but differences in affinity and half-life suggest differences in function. Serum IL-4/sIL-4Rα complexes rapidly dissociate, releasing active IL-4, whereas sIL-13Rα2 and IL-13 form a stable complex that has a considerably longer half-life than uncomplexed IL-13, sIL-13Rα2, IL-4, or sIL-4Rα. Approximately 25% of sIL-13Rα2 in serum is complexed to IL-13; this percentage and the absolute quantity of sIL-13Rα2 in serum increase considerably during a Th2 response. sIL-13Rα2 gene expression is up-regulated by both IL-4 and IL-13; the effect of IL-4 is totally IL-4Rα-dependent while the effect of IL-13 is partially IL-4Rα-independent. Inhalation of an IL-13/sIL-13Rα2 complex does not affect the expression of IL-13-inducible genes but increases the expression of two genes, Vnn1 and Pira-1, whose products activate APCs and promote neutrophilic inflammation. These observations suggest that sIL-4Rα predominantly sustains, increases, and diffuses the effects of IL-4, whereas sIL-13Rα2 limits the direct effects of IL-13 to the site of IL-13 production and forms a stable complex with IL-13 that may modify the quality and intensity of an allergic inflammatory response.

show abstract

IL-13 receptors and signaling pathways: An evolving web

Cited by 510 publications

References 133 publications

IL‐13 regulates cancer invasion and metastasis through IL‐13Rα2 via ERK/AP‐1 pathway in mouse model of human ovarian cancer

IL‐13 regulates cancer invasion and metastasis through IL‐13Rα2 via ERK/AP‐1 pathway in mouse model of human ovarian cancer

Opuntia humifusamodulates morphological changes characteristic of asthma via IL-4 and IL-13 in an asthma murine model

Differences in Expression, Affinity, and Function of Soluble (s)IL-4Rα and sIL-13Rα2 Suggest Opposite Effects on Allergic Responses

Contact Info

Product

Resources

About