TGF-β and IL-13 Synergistically Increase Eotaxin-1 Production in Human Airway Fibroblasts

Wenzel, Sally E.; Trudeau, John B.; Barnes, S.M.; Zhou, Xiaodong; Cundall, Meghan; Westcott, Jay Y.; McCord, Kelly; Chu, Hong Wei

doi:10.4049/jimmunol.169.8.4613

Cited by 119 publications

(101 citation statements)

References 23 publications

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“…For example, release of eotaxin in response to TGF-b and IL-13 can act as a chemoattractant for eosinophils [150]. TGF-binduced CCL-2 (monocyte chemoattractant protein-1) acts as a chemoattractant for monocytes [151].…”

Section: Contribution Of Tgf-b and Egf To Remodelling C Boxall Et Almentioning

confidence: 99%

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

Boxall

Holgate²,

Davies³

2006

Eur Respir J

226

187

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Asthma is increasing in prevalence in the developing world, affecting ,10% of the world's population. It is characterised by chronic lung inflammation and airway remodelling associated with wheezing, shortness of breath, acute bronchial hyperresponsiveness to a variety of innocuous stimuli and a more rapid decline in lung function over time.Airway remodelling, involving proliferation and differentiation of mesenchymal cells, particularly myofibroblasts and smooth muscle cells, is generally refractory to corticosteroids and makes a major contribution to disease chronicity. Transforming growth factor-b is a potent profibrogenic factor whose expression is increased in the asthmatic airways and is a prime candidate for the initiation and persistence of airway remodelling in asthma.This review highlights the role of transforming growth factor-b in the asthmatic lung, incorporating biosynthesis, signalling pathways and functional outcome. In vivo, however, it is the balance between transforming growth factor-b and other growth factors, such as epidermal growth factor, which will determine the extent of fibrosis in the airways.A fuller comprehension of the actions of transforming growth factor-b, and its interaction with other signalling pathways, such as the epidermal growth factor receptor signalling cascade, may enable development of therapies that control airway remodelling where there is an unmet clinical need.

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Section: Contribution Of Tgf-b and Egf To Remodelling C Boxall Et Almentioning

confidence: 99%

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

Boxall

Holgate²,

Davies³

2006

Eur Respir J

226

187

View full text Add to dashboard Cite

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“…The threshold cycle (Ct) was recorded for each sample and the comparative Ct method was used to represent the relative gene expression levels [15].…”

Section: Bronchoscopymentioning

confidence: 99%

Mycoplasma pneumoniaeinduces airway epithelial cell expression of MUC5AC in asthma

Kraft¹,

Adler²,

Ingram³

et al. 2007

Eur Respir J

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As excess mucin expression can contribute to the exacerbation of asthma, the present authors hypothesised that Mycoplasma pneumoniae significantly induces MUC5AC (the major airway mucin) expression in airway epithelial cells isolated directly from asthmatic subjects.A total of 11 subjects with asthma and six normal controls underwent bronchoscopy with airway brushing. Epithelial cells were cultured at an air-liquid interface and incubated with and without M. pneumoniae for 48 h, and in the presence and absence of nuclear factor (NF)-kB and a toll-like receptor (TLR)2 inhibitor. Quantitative PCR was performed for MUC5AC and TLR2 mRNA. MUC5AC protein and total protein were determined by ELISA.M. pneumoniae exposure significantly increased MUC5AC mRNA and protein expression after 48 h in epithelial cells isolated from asthmatic, but not from normal control subjects, at all concentrations as compared to unexposed cells. TLR2 mRNA expression was significantly increased in asthmatic epithelial cells at 4 h compared with unexposed cells. NF-kB and TLR2 inhibition reduced MUC5AC expression to the level of the unexposed control in both groups.Mycoplasma pneumoniae exposure significantly increased MUC5AC mRNA and protein expression preferentially in airway epithelial cells isolated from asthmatic subjects. The toll-like receptor 2 pathway may be involved in this process.

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“…The biopsy (and postmortem) lung tissue was processed as described previously (14). Briefly, the biopsy pieces were cultured until fibroblasts advanced out from the tissue.…”

Section: Fibroblast Culture and Experimentationmentioning

confidence: 99%

“…In addition to their fibrotic potential, fibroblasts release other mediators that are important in the pathogenesis of asthma (11)(12)(13). For instance, fibroblasts are an important source of eotaxin, a potent eosinophil chemoattractant (13,14). Aberrant or abnormal phenotypes of fibroblasts have been described in several fibrotic disorders (15).…”

mentioning

confidence: 99%

Regional Fibroblast Heterogeneity in the Lung

Kotaru

Schoonover²,

Trudeau³

et al. 2006

Am J Respir Crit Care Med

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Rationale: Excessive deposition of extracellular matrix occurs in proximal airways of individuals with asthma, but fibrosis in distal lung has not been observed. Whether differing fibrotic capacities of fibroblasts from these two regions contribute to this variability is unknown. Objectives: We compared morphologic and functional characteristics of fibroblasts isolated from proximal airways and distal lung parenchyma to determine phenotypic differences. Methods: Concurrent proximal airway and distal lung biopsies were obtained by bronchoscopy from subjects with asthma to isolate airway and distal lung fibroblasts, respectively. The following characteristics were compared: morphology, proliferation, ␣-smooth muscle actin expression, and synthesis of procollagen type I and eotaxin-1. Results: Airway fibroblasts (AFs) are morphologically distinct from distal lung fibroblasts (DLFs): they are larger (2.3-fold greater surface area vs. matched DLFs; p ϭ 0.02), stellate in appearance, and with more cytoplasmic projections compared with the spindleshaped DLFs. AFs synthesized more procollagen type I than did DLFs at baseline (twofold higher; p ϭ 0.003) and after transforming growth factor-␤ stimulation (1.4-fold higher; p ϭ 0.02). Similarly, AFs produced more eotaxin-1 than did DLFs at baseline (2.5-fold higher; p ϭ 0.004) and after interleukin-13 stimulation (13-fold higher; p ϭ 0.0001). In contrast, DLFs proliferate more than AFs with serum stimulation (about sixfold greater; p ϭ 0.03). Unstimulated DLFs also expressed more ␣-smooth muscle actin than did corresponding AFs (p ϭ 0.006). Conclusions: These studies suggest that at least two phenotypes of fibroblast exist in the lung. These phenotypic differences may partially explain the variable responses to injury and repair between proximal airways and distal lung/parenchyma in asthma and other respiratory diseases.

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TGF-β and IL-13 Synergistically Increase Eotaxin-1 Production in Human Airway Fibroblasts

Cited by 119 publications

References 23 publications

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

Mycoplasma pneumoniaeinduces airway epithelial cell expression of MUC5AC in asthma

Regional Fibroblast Heterogeneity in the Lung

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