Analysis of changes in expression of IL-4/IL-13/STAT6 pathway and correlation with the selected clinical parameters in patients with atopic asthma

Antczak, Adam; Domańska-Senderowska, Daria; Górski, Paweł; Pastuszak-Lewandoska, Dorota; Nielepkowicz-Goździńska, Agnieszka; Szewczyk, Karolina; Kurmanowska, Zofia; Kiszałkiewicz, Justyna; Brzeziańska-Lasota, Ewa

doi:10.1177/0394632015623794

Cited by 26 publications

(23 citation statements)

References 42 publications

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“…Supporting our findings, Bao et al [20], Shi et al [21], Wu et al, [22] and Nesi et al [23] revealed a significant increase in IL-4 in ovalbumininduced asthmatic mice compared to the control. Our finding may also be reinforced in the light of observations of Antczak et al [5] who found higher mRNA level of IL-4 and IL-13 genes in asthmatic patients when compared to controls. But they did not find statistically significant differences between controlled and uncontrolled bronchial asthma, even the highest IL-4 expression was recognized in uncontrolled atopic asthma patients.…”

Section: Discussionsupporting

confidence: 85%

“…Many family studies, through genome-wide linkage studies, confirmed the involvement of genetic predisposition in the development of atopy in asthmatic patients [4]. The elevated IgE production in asthmatic patients results in promotion of acute hypersensitivity responses, chronic eosinophil-predominant allergic inflammation with T helper-2 (Th2) cells cytokine production [5].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, IL-4 plays a pivotal role in phenotypic changes of bronchial asthma, such as airway hyperresponsiveness, eosinophil infiltration, and mucus overproduction [6]. Also STAT6, the signaling molecule from JAK/STAT pathway, activated by IL-4 and IL-13 cytokines, plays an important role in IgE production and allergic airway inflammation [5].…”

Section: Introductionmentioning

confidence: 99%

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Association of STAT6 rs324011 Gene Polymorphism with Susceptibility of Atopic Bronchial Asthma in Egyptian Children

El-Gohary¹,

Wagih²,

Hamouda³

et al. 2018

Biochem Mol biol J

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Background: Bronchial asthma is a common disease with multiple determinants that include genetic variation. Signal transducer and activator of transcription 6 (STAT6) is a central molecule in the signal transduction pathway used by interleukin-4 (IL-4) in immunoglobulin E (IgE) isotype switching. Study Objective was to investigate whether single nucleotide polymorphism (SNP) in STAT6 is associated with atopic asthma susceptibility in Egyptian children and to correlate the effect of STAT6 gene polymorphism on IL-4 and total IgE levels.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of STAT6 rs324011 Gene Polymorphism with Susceptibility of Atopic Bronchial Asthma in Egyptian Children

El-Gohary¹,

Wagih²,

Hamouda³

et al. 2018

Biochem Mol biol J

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“…In asthma, Th2-related cytokines such as IL-4 [35–37], IL-5 [38], and IL-13 [35,37] significantly increase; the development of antibodies against Th2-related cytokines is an active field of research [39]. Changes in Th17 cells correlate with asthma induction, making it important to analyze Th-17 proteins such as TNF-α, IL-6, and IL-1β [40].…”

Section: Discussionmentioning

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

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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

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“…The biological function of IL-4 principally comprises increasing B cell major histocompatibility complex class II molecule expression, promoting resting B cell FceR expression, elevating secretion of IgE and IgG1 in the activation of B cells, and stimulating IgG to IgE class switching in an autocrine manner to facilitate the differentiation of Th2 cells, while inhibiting Th1 cell proliferation and the Th1 response (Antczak et al, 2016;Pattnaik et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Role of interleukin-4 genetic polymorphisms and environmental factors in the risk of asthma in children

Zeng

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Asthma is an allergic disease characterized by hyperresponsiveness and chronic inflammation of the airway. The interleukin-4 (IL-4) gene and its single nucleotide polymorphisms are associated with asthma susceptibility in children. A case-control study was performed to evaluate the relationship between asthma risk and the IL-4 rs2243250 (589 C/T) and rs2070874 (107 T/C), and IL-4 receptor (IL-4R) rs1801275 (576 Q/R) polymorphisms in 317 childhood asthma patients and 351 healthy children as controls. Polymerase chain reaction amplification and sequencing was performed. The effects of interactions between the genes of interest and environmental factors were also analyzed. IL-4 rs2243250 and rs2070874 allele and genotype frequencies did not significantly differ between the asthma and control groups (P > 0.05), but those of IL-4R rs1801275 did (P < 0.05). The RR genotype and R allele of this IL-4R variant were significantly associated with asthma risk, with odds ratios (ORs; and 95% confidence intervals) of 2.97 (2.08-4.25) and 2.99 (2.32-3.85), respectively. Logistic regression analysis showed that the IL-4R 576 Q/R RR genotype demonstrated a positive interaction with environments associated with smoking or pets in its effect on asthma risk, with ORs of 2.18 (P = 0.02) and 2.29 (P = 0.01), respectively. Our results suggest that the IL-4R rs1801275 polymorphism is associated with childhood asthma, and the RR genotype confers a high risk of developing this condition. This variant exhibited positive interactions with environments in which smoking or pets were present in increasing the risk of childhood asthma.

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Analysis of changes in expression of IL-4/IL-13/STAT6 pathway and correlation with the selected clinical parameters in patients with atopic asthma

Abstract: Our data support the role of Th2 cytokines (IL-4, IL-13) and STAT6 in Th1/Th2 imbalance and highlight the etiological relationship between IL-4/IL-13/STAT6 signaling and atopy and asthma.

Cited by 26 publications

References 42 publications

Association of STAT6 rs324011 Gene Polymorphism with Susceptibility of Atopic Bronchial Asthma in Egyptian Children

Association of STAT6 rs324011 Gene Polymorphism with Susceptibility of Atopic Bronchial Asthma in Egyptian Children

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

Role of interleukin-4 genetic polymorphisms and environmental factors in the risk of asthma in children

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