Mechanisms of asthma and allergic inflammationIncreased TGF-β2 in severe asthma with eosinophilia
Section snippets
Subjects
Severe asthma was defined by: (1) FEV1 of ≤70% predicted on more than 1 occasion over the previous year, (2) 10 mg/d prednisone or equivalent for at least 50% of the previous year while taking other standard asthma medications, (3) >2 urgent care visits for asthma in the previous year, and (4) ongoing symptoms.3 Patients with severe asthma were divided into those with persistent tissue eosinophilia (>22 eosinophils/mm2 tissue, equivalent to ≥2 SDs from the mean value measured in normal
Subject characteristics
Eighty-three subjects, including 24 eosinophil+ (eos+) and 24 eosinophil− (eos−) subjects with severe asthma, were enrolled in this study (Table I). Control subjects were younger than subjects with asthma (overall P = .03). There was no difference in oral steroid doses between the 2 severe groups, and ∼25% subjects in both groups were only on high-dose inhaled corticosteroids at the time of bronchoscopy.
Tissue expression of TGF-β1, TGF-β2, and TGF-β3
TGF-β1+ and TGF-β3+ cell counts were similar in all groups (Fig 1, A and C). In contrast,
Discussion
The current study, designed to evaluate specifically TGF-β isoforms and TGF-β–related pathways in asthma, is the first to identify TGF-β2 as a prominent TGF-β isoform in severe asthma and its association with eosinophils. TGF-β2 expression in eosinophils was specific to severe asthma, because TGF-β2 could not be colocalized to tissue eosinophils in mild/nonsteroid-treated subjects with asthma or normal subjects. This study further reports evidence for activation of downstream TGF-β–related
References (43)
- et al.
Subepithelial fibrosis in the bronchi of asthmatics
Lancet
(1989) - et al.
Matrix metalloproteinases (MMPs) and their physiological inhibitors (TIMPs) are differentially expressed during excisional skin wound repair
Exp Cell Res
(1998) - et al.
Balance in asthma between matrix metalloproteinases and their inhibitors
J Allergy Clin Immunol
(1999) - et al.
The role of transforming growth factor beta in lung development and disease
Chest
(2004) - et al.
TGF-beta isoforms in renal fibrogenesis
Kidney Int
(2003) - et al.
Distinguishing severe asthma phenotypes: role of age at onset and eosinophilic inflammation
J Allergy Clin Immunol
(2004) - et al.
Peripheral blood and airway tissue expression of transforming growth factor beta by neutrophils in asthmatic subjects and normal control subjects
J Allergy Clin Immunol
(2000) - et al.
Transforming growth factor β2 induces bronchial epithelial mucin expression in asthma
Am J Pathol
(2004) - et al.
Expression and regulation of tissue inhibitor of metalloproteinase-1 and matrix metalloproteinases by intestinal myofibroblasts in inflammatory bowel disease
Am J Pathol
(2003) - et al.
Mediation of transforming growth factor-beta(1)-stimulated matrix contraction by fibroblasts: a role for connective tissue growth factor in contractile scarring
Am J Pathol
(2003)
Peroxisome proliferator-activated receptor gamma inhibits transforming growth factor beta-induced connective tissue growth factor expression in human aortic smooth muscle cells by interfering with Smad3
J Biol Chem
Cellular infiltration of the airways in asthma of varying severity
Am J Respir Crit Care Med
Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics
Am J Respir Crit Care Med
Expression and activation of 15-lipoxygenase pathway in severe asthma: relationship to eosinophilic phenotype and collagen deposition
Clin Exp Allergy
Eosinophil-associated TGF-beta1 mRNA expression and airways fibrosis in bronchial asthma
Am J Respir Cell Mol Biol
Interleukin-4 and interleukin-13-enchanced transforming growth factor-beta2 production in cultured human bronchial epithelial cells is attenuated by interferon-gamma
Am J Respir Cell Mol Biol
Involvement of the epidermal growth factor receptor in epithelial repair in asthma
FASEB J
Repression of tissue inhibitor of matrix metalloproteinase expression by all-trans-retinoic acid in rat bone cell populations: comparison with transforming growth factor-beta 1
J Cell Physiol
Regulation of tissue inhibitor of matrix metalloproteinase expression
Ann N Y Acad Sci
Transforming growth factor beta (TGF-beta) and dexamethasone have direct opposing effects on collagen metabolism in low passage human dermal fibroblasts in vitro
Growth Factors
Tissue inhibitor of metalloproteinase-1 levels in bronchoalveolar lavage fluid from asthmatic subjects
Am J Respir Crit Care Med
Cited by (124)
Eosinophils and tissue remodeling: Relevance to airway disease
2023, Journal of Allergy and Clinical ImmunologyERBIN and phosphoglucomutase 3 deficiency
2023, Current Opinion in ImmunologyQuestionnaire for diagnosing asthma-COPD overlap in COPD: Development of ACO screening questionnaire (ACO-Q)
2023, Allergology InternationalDual role for CXCR3 and CCR5 in asthmatic type 1 inflammation
2022, Journal of Allergy and Clinical ImmunologyBone morphogenetic protein-2 as a novel biomarker for refractory chronic rhinosinusitis with nasal polyps
2021, Journal of Allergy and Clinical Immunology
Supported by National Institutes of Health grants HL-64087, AI-40600, RR-00051, and ALA of Colorado, Oklahoma, and Alaska.