Genetic Polymorphism of Transforming Growth Factor β1 and Tumor Necrosis Factor α Is Associated With Asthma and Modulates the Severity of Asthma

Chiang, Chiao–Hsi; Chuang, Chiao–Hui; Liu, Shiou-Ling; Shen, Horng-Der

doi:10.4187/respcare.02187

Cited by 23 publications

(17 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies identified polymorphisms in the TGFβ1 locus that segregate with allergy and asthma (33–37). The suspicion that TGFβ1 might contribute to allergic disease prompted investigations into its effects on IgE-mediated mast cell responses.…”

Section: Discussionmentioning

confidence: 99%

TGF-β1 Suppresses IL-33–Induced Mast Cell Function

Ndaw

Abebayehu

Spence

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

TGFβ1 is involved in many pathological conditions, including autoimmune disorders, cancer, cardiovascular and allergic diseases. We have previously found that TGFβ1 can suppress IgE-mediated mast cell activation of human and mouse mast cells. IL-33 is a member of the IL-1 family capable of inducing mast cell responses and enhancing IgE-mediated activation. In this study, we investigated the effects of TGFβ on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGFβ −1, −2, or −3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13 and MCP-1, in a concentration-dependent manner. TGFβ1 inhibited IL-33-mediated Akt and ERK phosphorylation as well as NFκB- and AP-1-mediated transcription. These effects were functionally important, as TGFβ1 injection suppressed IL-33-induced systemic cytokines in vivo and inhibited IL-33-mediated cytokine release from human mast cells. TGFβ1 also suppressed the combined effects of IL-33 and IgE-mediated activation on mouse and human mast cells. The role of IL-33 in the pathogenesis of allergic diseases is incompletely understood. These findings, consistent with our previously reported effects of TGFβ1 on IgE-mediated activation, demonstrate that TGFβ1 can provide broad inhibitory signals to activated mast cells.

show abstract

Section: Discussionmentioning

confidence: 99%

TGF-β1 Suppresses IL-33–Induced Mast Cell Function

Ndaw

Abebayehu

Spence

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Gene polymorphisms in the TGF-ß1 promoter region are associated with the development of asthma [9,132]. Several single nucleotide polymorphisms (SNPs) are associated with peripheral blood eosinophilia in asthmatic patients [133].…”

Section: Genetic Tgf-ß Modifiersmentioning

confidence: 99%

Transforming growth factor β and severe asthma: A perfect storm

Al‐Alawi

Hassan

Chotirmall

2014

Respiratory Medicine

134

108

View full text Add to dashboard Cite

Asthma is a chronic inflammatory airway disease involving complex interplay between resident and infiltrative cells, which in turn are regulated by a wide range of host mediators. Identifying useful biomarkers correlating with clinical symptoms and degree of airway obstruction remain important to effective future asthma treatments. Transforming growth factor β (TGF-β) is a major mediator involved in pro-inflammatory responses and fibrotic tissue remodeling within the asthmatic lung. Its role however, as a therapeutic target remains controversial. The aim of this review is to highlight its role in severe asthma including interactions with adaptive T-helper cells, cytokines and differentiation through regulatory T-cells. Associations between TGF-β and eosinophils will be addressed and the effects of genetic polymorphisms of the TGF-β1 gene explored in the context of asthma. We highlight TGF-β1 as a potential future therapeutic target in severe asthma including its importance in identifying emerging clinical phenotypes in asthmatic subjects who may be suitable for individualized therapy through TGF-β modulation.

show abstract

“…MAPK signaling pathways are known to be involved in airway inflammation and the regulation of immune cells, which are the hallmark features of asthma [49,50,53]. In addition, genetic variants of MAPK1 might be involved in regulating cytokine levels in asthma patients, which might modulate the severity of asthma [54][55][56].…”

Section: Discussionmentioning

confidence: 99%

Bisphenol a Exposure, DNA Methylation, and Asthma in Children

Yang

Karmaus

Yang³

et al. 2020

IJERPH

View full text Add to dashboard Cite

Epidemiological studies have reported the relationship between bisphenol A (BPA) exposure and increased prevalence of asthma, but the mechanisms remain unclear. Here, we investigated whether BPA exposure and DNA methylation related to asthma in children. We collected urinary and blood samples from 228 children (Childhood Environment and Allergic Diseases Study cohort) aged 3 years. Thirty-three candidate genes potentially interacting with BPA exposure were selected from a toxicogenomics database. DNA methylation was measured in 22 blood samples with top-high and bottom-low exposures of BPA. Candidate genes with differential methylation levels were validated by qPCR and promoter associated CpG islands have been investigated. Correlations between the methylation percentage and BPA exposure and asthma were analyzed. According to our findings, MAPK1 showed differential methylation and was further investigated in 228 children. Adjusting for confounders, urinary BPA glucuronide (BPAG) level inversely correlated with MAPK1 promoter methylation (β = −0.539, p = 0.010). For the logistic regression analysis, MAPK1 methylation status was dichotomized into higher methylated and lower methylated groups with cut off continuous variable of median of promoter methylation percentage (50%) while performing the analysis. MAPK1 methylation was lower in children with asthma than in children without asthma (mean ± SD; 69.82 ± 5.88% vs. 79.82 ± 5.56%) (p = 0.001). Mediation analysis suggested that MAPK1 methylation acts as a mediation variable between BPA exposure and asthma. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation.

show abstract

Genetic Polymorphism of Transforming Growth Factor β1 and Tumor Necrosis Factor α Is Associated With Asthma and Modulates the Severity of Asthma

Cited by 23 publications

References 31 publications

TGF-β1 Suppresses IL-33–Induced Mast Cell Function

TGF-β1 Suppresses IL-33–Induced Mast Cell Function

Transforming growth factor β and severe asthma: A perfect storm

Bisphenol a Exposure, DNA Methylation, and Asthma in Children

Contact Info

Product

Resources

About