Transforming Growth Factor-β1 Suppresses Airway Hyperresponsiveness in Allergic Airway Disease

Alcorn, John F.; Rinaldi, Lisa; Jaffe, Elizabeth F.; Loon, Mirjam van; Bates, Jason H. T.; Janssen–Heininger, Yvonne M. W.; Irvin, Charles G.

doi:10.1164/rccm.200702-334oc

Cited by 109 publications

(105 citation statements)

References 58 publications

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“…Consistent with our findings in children with asthma, Ogawa and colleagues reported that the CC genotype of SNP rs1800469 was associated with increased airway responsiveness in 590 adults with COPD (33). If allele C of SNP rs1800469 is in fact correlated with reduced levels of TGF-b1 (see below), our findings and those of Ogawa and colleagues are consistent with those of murine models of allergic airway inflammation that suggest that antagonism of TGF-b1 results in increased airway responsiveness (34), and that intratracheal administration of TGF-b1 inhibits antigeninduced airway responsiveness (35). * All analyses were conducted under the assumption of a dominant genetic model.…”

Section: Discussionsupporting

confidence: 91%

Variants in TGFB1, Dust Mite Exposure, and Disease Severity in Children with Asthma

Sharma¹,

Raby²,

Hunninghake³

et al. 2009

Am J Respir Crit Care Med

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Rationale: Polymorphisms in the gene for transforming growth factor-b1 (TGFB1) have been associated with asthma, but not with airway responsiveness or disease exacerbations in subjects with asthma. Objectives: To test for association between single nucleotide polymorphisms (SNPs) in TGFB1 and markers of asthma severity in childhood. Methods: We tested for the association between nine SNPs in TGFB1 and indicators of asthma severity (lung function, airway responsiveness, and disease exacerbations) in two cohorts: 416 Costa Rican parent-child trios and 465 families of non-Hispanic white children in the Childhood Asthma Management Program (CAMP). We also tested for the interaction between these polymorphisms and exposure to dust mite allergen on asthma severity. Measurements and Main Results: The A allele of promoter SNP rs2241712 was associated with increased airway responsiveness in Costa Rica (P 5 0.0006) and CAMP (P 5 0.005), and the C allele of an SNP in the promoter region (rs1800469) was associated with increased airway responsiveness in both cohorts (P < 0.01). Dust mite exposure modified the effect of the C allele of exonic SNP rs1800471 on airway responsiveness (P 5 0.03 for interactions in both cohorts). The T allele of a coding SNP (rs1982073) was associated with a reduced risk of asthma exacerbations in Costa Rica (P 5 0.009) and CAMP (P 5 0.005). Dust mite exposure also significantly modified the effect of the A allele of the promoter SNP rs2241712 on asthma exacerbations in both cohorts. Conclusions: SNPs in TGFB1 are associated with airway responsiveness and disease exacerbations in children with asthma. Moreover, dust mite exposure may modify the effect of TGFB1 SNPs on airway responsiveness and asthma exacerbations.

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Section: Discussionsupporting

confidence: 91%

Variants in TGFB1, Dust Mite Exposure, and Disease Severity in Children with Asthma

Sharma¹,

Raby²,

Hunninghake³

et al. 2009

Am J Respir Crit Care Med

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“…Accordingly, airway reactivity was shown to correlate negatively with airway wall thickness in humans with asthma (155,175). Similar observations were made in a mouse model of asthma (2). Therefore, even if thickening due to fibrosis can theoretically increase airway narrowing in response to spasmogens because of geometrical effects, airway wall stiffening due to thicker or more fibrotic wall may well protect against AHR.…”

Section: Reduced Asm-load Due To Remodelingsupporting

confidence: 54%

Airway Smooth Muscle in Asthma Symptoms: Culprit but Maybe Innocent

Bossé¹,

Paré²,

Boss³

2012

Lung Diseases - Selected State of the Art Reviews

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“…In contrast, Alcorn and coworkers have indicated that attenuated airway remodeling does not impact airway inflammatory responses or AHR (27). In particular, these authors reported that neutralization of TGF-b1 responses in the lungs of OVA-treated mice suppressed airway fibrosis while increasing AHR; neutralization had no affect on airway inflammation (27). Collectively, these studies demonstrate that airway inflammation, remodeling, and hyperresponsiveness may not be directly interrelated.…”

Section: Discussionmentioning

confidence: 80%

“…Similarly, Leigh and coworkers have shown that mice that undergo chronic allergen exposure exhibit structural changes that are associated with AHR in the absence of cellular inflammation (26). In contrast, Alcorn and coworkers have indicated that attenuated airway remodeling does not impact airway inflammatory responses or AHR (27). In particular, these authors reported that neutralization of TGF-b1 responses in the lungs of OVA-treated mice suppressed airway fibrosis while increasing AHR; neutralization had no affect on airway inflammation (27).…”

Section: Discussionmentioning

confidence: 99%

Acute Exercise Decreases Airway Inflammation, but Not Responsiveness, in an Allergic Asthma Model

Hewitt

Creel²,

Estell³

et al. 2009

Am J Respir Cell Mol Biol

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Previous studies have suggested that the asthmatic responses of airway inflammation, remodeling, and hyperresponsiveness (AHR) are interrelated; in this study, we used exercise to examine the nature of this interrelationship. Mice were sensitized and challenged with ovalbumin (OVA); mice were then exercised via running on a motorized treadmill at a moderate intensity. Data indicate that, within the lungs of OVA-treated mice, exercise attenuated the production of inflammatory mediators, including chemokines KC, RANTES, and MCP-1 and IL-12p40/p80. Coordinately, OVA-treated and exercised mice displayed decreases in leukocyte infiltration, including eosinophils, as compared with sedentary controls. Results also show that a single bout of exercise significantly decreased phosphorylation of the NFkB p65 subunit, which regulates the gene expression of a wide variety of inflammatory mediators. In addition, OVA-treated and exercised mice exhibited decreases in the levels of Th2-derived cytokines IL-5 and IL-13 and the prostaglandin PGE 2 , as compared with sedentary controls. In contrast, results show that a single bout of exercise had no effect on AHR in OVA-treated mice challenged with increasing doses of aerosolized methacholine (0-50 mg/ml) as compared with sedentary mice. Exercise also had no effect on epithelial cell hypertrophy, mucus production, or airway wall thickening in OVA-treated mice as compared with sedentary controls. These findings suggest that a single bout of aerobic exercise at a moderate intensity attenuates airway inflammation but not AHR or airway remodeling in OVA-treated mice. The implication of these findings for the interrelationship between airway inflammation, airway remodeling, and AHR is discussed.

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Transforming Growth Factor-β1 Suppresses Airway Hyperresponsiveness in Allergic Airway Disease

Cited by 109 publications

References 58 publications

Variants in TGFB1, Dust Mite Exposure, and Disease Severity in Children with Asthma

Variants in TGFB1, Dust Mite Exposure, and Disease Severity in Children with Asthma

Airway Smooth Muscle in Asthma Symptoms: Culprit but Maybe Innocent

Acute Exercise Decreases Airway Inflammation, but Not Responsiveness, in an Allergic Asthma Model

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