Platelet‐derived growth factor in asthma

Chanez, Pascal; Vignola, María Belén; Stenger, Richard J.; Vic, P.; Michel, François; Bousquet, Jean

doi:10.1111/j.1398-9995.1995.tb02493.x

Cited by 41 publications

(18 citation statements)

References 38 publications

(31 reference statements)

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“…SMC are a primary source of PDGF-AA (1). Levels of PDGF-AA are not raised in asthma (2). However, PDGF has been implicated in proliferation and migration of SMC in atherosclerosis (5).…”

Section: Discussionmentioning

confidence: 99%

Production of Basic Fibroblast Growth Factor and Interleukin 6 by Human Smooth Muscle Cells following Infection with Chlamydia pneumoniae

et al. 2000

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Chlamydia pneumoniae infection has been associated with asthma and atherosclerosis. Smooth muscle cells represent host cells for chlamydiae during chronic infection. In this study we demonstrated that C. pneumoniae infection of human smooth muscle cells in vitro increased production of interleukin 6 (IL-6) and basic fibroblast growth factor (bFGF) as shown by reverse transcription-PCR, immunoblotting, and enzyme-linked immunosorbent assay. In contrast, levels of platelet-derived growth factor A-chain mRNA were not affected after infection. The stimulation of bFGF and IL-6 production was most effective when viable chlamydiae were used as inoculum. Furthermore, inhibition of bacterial protein synthesis with chloramphenicol prevented up-regulation of IL-6 and bFGF in infected cells. Addition of IL-6 antibody to infected cultures diminished bFGF expression, indicating involvement of produced IL-6. These findings suggest that chlamydial infection of smooth muscle cells elicits a cytokine response that may contribute to structural remodeling of the airway wall in chronic asthma and to fibrous plaque formation in atherosclerosis.Chlamydia pneumoniae (in a recent paper renamed Chlamydophila pneumoniae) is an obligate intracellular bacterial pathogen that causes acute respiratory infections (9). Moreover, chronic or recurrent chlamydial infections have been associated with asthma and atherosclerosis. C. pneumoniae has a biphasic growth cycle. Infectious elementary bodies (EBs) enter the host cell and differentiate into reticulate bodies (RBs). These RBs divide by binary fission within the expanding endosome, resulting in development of an intracellular inclusion. After a period of growth, RBs reorganize into new EBs that are released by host cell lysis or exocytosis. Chronic infections are obviously associated with lytic and nonlytic phases in which chlamydiae do not replicate.Evidence for C. pneumoniae in asthma comes from serodiagnostic studies and culture (3,13,14). The association of asthma with elevated specific immunoglobulin G (IgG) antibodies seems to be strongest for nonatopic long-standing asthma (37). These studies suggest an important role for chronic infection as a promoting factor that would produce a tendency to severe chronic asthma. It is possible that chlamydiae amplify the inflammation in patients with early mild asthma, leading to permanent changes in the airways (37). Furthermore, C. pneumoniae can probably initiate adult-onset asthma (15). Activation of a synthetic phenotype of smooth muscle cells (SMC) plays an important role in the pathogenesis of asthma (17). Chronic inflammation and cycles of repair in chronic asthma lead to structural remodeling of the airway wall. This process is characterized by smooth muscle hyperplasia and hypertrophy and by thickening of the basement membrane with deposition of collagen types III and V (31, 33). The increase in the amount of SMC results in an enhanced contractile response and in irreversible airflow obstruction.The pathogenesis of atherosclerosis also invo...

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“…SMC are a primary source of PDGF-AA (1). Levels of PDGF-AA are not raised in asthma (2). However, PDGF has been implicated in proliferation and migration of SMC in atherosclerosis (5).…”

Section: Discussionmentioning

confidence: 99%

Production of Basic Fibroblast Growth Factor and Interleukin 6 by Human Smooth Muscle Cells following Infection with Chlamydia pneumoniae

et al. 2000

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“…All the mitogens are present in the airways (4,15,24). However, their levels in the airways of asthmatics are likely to vary depending on the degree of inflammatory cell activation and vascular leakage occurring locally.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of serum potentiation of GM-CSF production by human airway smooth muscle cells

Lalor¹,

Truong²,

Henness³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Inflammation and vascular leakage are prevalent in asthma. This study aimed to elucidate the mechanisms involved in serum potentiation of cytokine-induced granulocyte macrophage colony stimulating factor (GM-CSF) production by human airway smooth muscle cells and to identify possible factors responsible. Serum-deprived cells at low density were stimulated with TNF-α and IL-1β for 24 h. Human AB serum (10%), inhibitors of RNA and protein synthesis or specific signaling molecules, or known smooth muscle mitogens were then added for 24 h. Culture supernatants were analyzed for GM-CSF levels, and cells were harvested to assess viability, cell cycle progression, GM-CSF-specific mRNA content, and p38 phosphorylation. Serum potentiated GM-CSF release when added before, together with (maximal), or after the cytokines. The potentiation involved both new GM-CSF-specific mRNA production and protein synthesis. The mitogens IGF, PDGF, and thrombin all potentiated GM-CSF release, and neutralizing antibodies for EGF, IGF, and PDGF reduced the serum potentiation. Inhibitor studies ruled as unlikely the involvement of p70S6kinase and the MAPK p42/p44, two signaling pathways implicated in proliferation, and the involvement of the MAPK JNK, while establishing roles for p38 MAPK and NF-κB in the potentiation of GM-CSF release. Detection of significant p38 phosphorylation in response to serum stimulation, through Western blotting, further demonstrated the involvement of p38. These studies have provided evidence to support p38 being targeted to interrupt the cycle of inflammation, vascular leakage and cytokine production in asthma.

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“…It is known that hyperplasia of smooth muscle in animal models [9][10][11] and both hyperplasia and hypertrophy in airway specimens from human subjects [12,13] contribute to the increase in ASM mass. It has also been proposed that migration of subepithelial myofibroblasts may add to the tissue mass [7].The mechanism of the growth response of muscle is quite uncertain, although several descriptive studies of growth factor expression in human airway tissues have been reported [14][15][16] and many growth factors have been demonstrated to have mitogenic effects on ASM in culture [17][18][19][20]. Cysteinyl (cys)-leukotrienes (LTs) are known to be involved in allergen-induced ASM cell proliferation in vivo [21,22] but in vitro these substances are weak mitogens for ASM [23,24].…”

mentioning

confidence: 99%

“…The mechanism of the growth response of muscle is quite uncertain, although several descriptive studies of growth factor expression in human airway tissues have been reported [14][15][16] and many growth factors have been demonstrated to have mitogenic effects on ASM in culture [17][18][19][20]. Cysteinyl (cys)-leukotrienes (LTs) are known to be involved in allergen-induced ASM cell proliferation in vivo [21,22] but in vitro these substances are weak mitogens for ASM [23,24].…”

mentioning

confidence: 99%

The epidermal growth factor receptor mediates allergic airway remodelling in the rat

Tamaoka¹,

Hassan²,

McGovern³

et al. 2008

European Respiratory Journal

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The chronicity of bronchial asthma is attributed to persistent airway inflammation and to a variety of structural changes, or remodelling, that includes smooth muscle and goblet cell hyperplasia.To investigate the mechanisms of airway remodelling, the current authors used an established allergen (ovalbumin; OVA)-driven rodent model (the Brown Norway rat).Brown Norway rats were sensitised to OVA and challenged three times at 5-day intervals to evoke airway remodelling. The effects of an epidermal growth factor (EGF) receptor inhibitor, AG1478, and a cysteinyl leukotriene-1 receptor antagonist, montelukast, on epithelial and airway smooth muscle (ASM) cell proliferation in vivo in response to repeated OVA challenge were tested. Three challenges with leukotriene (LT)D 4 were given, to examine their effects on remodelling with and without AG1478 pretreatment.OVA challenges caused ASM hyperplasia, with an increase in mass, epithelial cell proliferation and goblet cell proliferation. AG1478 prevented the changes, as did montelukast. Multiple OVA challenges increased heparin-binding EGF-like growth factor but not EGF expression by airway epithelium. LTD 4 reproduced the changes in remodelling induced by OVA and this was blocked by AG1478.Allergen-induced airway epithelial and airway smooth muscle remodelling is mediated by cysteinyl leukotrienes via the cysteinyl leukotriene-1 receptor with downstream effects on the epidermal growth factor receptor axis.KEYWORDS: Allergy, inflammation, lung, signal transduction A sthmatic airways often show extensive and complex remodelling [1][2][3][4]. The growth of smooth muscle has the potential to have the most significant pathophysiological consequences through excessive airway narrowing and airway hyperresponsiveness [5,6]. Increase in airway smooth muscle (ASM) in the airways has been associated with the severity of asthma [3,7], and when present in excess in the large airways is associated with mortality [8]. It is known that hyperplasia of smooth muscle in animal models [9][10][11] and both hyperplasia and hypertrophy in airway specimens from human subjects [12,13] contribute to the increase in ASM mass. It has also been proposed that migration of subepithelial myofibroblasts may add to the tissue mass [7].The mechanism of the growth response of muscle is quite uncertain, although several descriptive studies of growth factor expression in human airway tissues have been reported [14][15][16] and many growth factors have been demonstrated to have mitogenic effects on ASM in culture [17][18][19][20]. Cysteinyl (cys)-leukotrienes (LTs) are known to be involved in allergen-induced ASM cell proliferation in vivo [21,22] but in vitro these substances are weak mitogens for ASM [23,24]. In the sensitised mouse, cys-LT 1 receptor (cys-LT 1 R) antagonism prevents an increase in ASM thickening after repeated allergen challenge [25,26]. It is possible that the effects of cys-LTs in vivo are indirect and mediated by altering the expression of or potentiating the effects of tyrosi...

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Platelet‐derived growth factor in asthma

Cited by 41 publications

References 38 publications

Production of Basic Fibroblast Growth Factor and Interleukin 6 by Human Smooth Muscle Cells following Infection with Chlamydia pneumoniae

Production of Basic Fibroblast Growth Factor and Interleukin 6 by Human Smooth Muscle Cells following Infection with Chlamydia pneumoniae

Mechanisms of serum potentiation of GM-CSF production by human airway smooth muscle cells

The epidermal growth factor receptor mediates allergic airway remodelling in the rat

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