Effects of interleukin-1β, interleukin-13 and transforming growth factor-β on gene expression in human airway smooth muscle using gene microarrays

Járai, Gábor; Sukkar, Maria B.; Garrett, Sarah; Duroudier, Nathalie P.; Westwick, John; Adcock, Ian M.; Chung, Kian Fan

doi:10.1016/j.ejphar.2004.06.055

Cited by 51 publications

(54 citation statements)

References 37 publications

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“…Thus, in ASMC, the release of GM-CSF, IL-8, and RANTES induced by IL-1␤ or TNF-␣ is dependent on JNK activation (34). IL-1␤ is also able to induce a range of other gene classes in ASMC, including proteases, enzymes, cytokine receptors, and transcription factors (35), which could be regulated by corticosteroids through induction of MKP-1. Therefore, our results that relate specifically to GRO-␣ regulation may have wider implications as a mechanism of effect of corticosteroids in ASMC.…”

Section: Discussionmentioning

confidence: 99%

Corticosteroid Inhibition of Growth-Related Oncogene Protein-α via Mitogen-Activated Kinase Phosphatase-1 in Airway Smooth Muscle Cells

Issa

Xie

Khorasani

et al. 2007

The Journal of Immunology

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Expression of the inflammatory chemokine, growth-related oncogene protein-α (GRO-α), from airway smooth muscle cells (ASMC) is regulated by pathways involving NF-κB and MAPK activation. We determined the effects of dexamethasone on GRO-α induced by IL-1β or TNF-α with respect to the role of MAPK pathways and of MAPK phosphatase-1 (MKP-1). Human ASMC were studied in primary culture at confluence. Dexamethasone (10−8–10−5 M) partially inhibited GRO-α expression and release induced by IL-1β and TNF-α; this was associated with an inhibition of JNK, but not of p38 or ERK phosphorylation. Together with IL-1β or TNF-α, dexamethasone rapidly induced mRNA and protein expression of MKP-1, which dephosphorylates MAPKs. Using MKP-1 small interfering RNA (siRNA) to block the expression of IL-1β- and dexamethasone-induced MKP-1 by 50%, JNK phosphorylation was doubled. The inhibitory effect of dexamethasone on GRO-α release was partially reversed in ASMC treated with MKP-1 siRNA compared with those treated with scrambled siRNA. In contrast, overexpression of MKP-1 led to a reduction in IL-1β-induced release of GRO-α, but the inhibitory effects of dexamethasone were preserved. Nuclear translocation of the glucocorticoid receptor was increased in ASMC exposed to dexamethasone and IL-1β. Using chromatin immunoprecipitation assay, glucocorticoid receptor binding to the MKP-1 promoter was increased by IL-1β and dexamethasone compared with either alone. Glucocorticoids and IL-1β or TNF-α modulate GRO-α release partly through the inhibition of JNK pathway, resulting from an up-regulation of MKP-1 expression.

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Section: Discussionmentioning

confidence: 99%

Corticosteroid Inhibition of Growth-Related Oncogene Protein-α via Mitogen-Activated Kinase Phosphatase-1 in Airway Smooth Muscle Cells

Issa

Xie

Khorasani

et al. 2007

The Journal of Immunology

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“…In the context of allergen provocation models, several potential mechanisms have been repeatedly hypothesized to underlie many of these pathologies in both patients as well as mouse models, including IL-13 expression (46), TGF-␤ activities in the lung (47), the production of small molecule mediators of inflammation such as cysteinyl (cys-) leukotrienes (48) or leukotriene B 4 (49), and the release of other tissue-damaging molecules (e.g., cationic granule proteins (1,50)). However, for many of these mechanisms, their relative importance and relevant cellular source(s) in the lung have remained debatable and/or unclear.…”

Section: Discussionmentioning

confidence: 99%

Coexpression of IL-5 and Eotaxin-2 in Mice Creates an Eosinophil-Dependent Model of Respiratory Inflammation with Characteristics of Severe Asthma

Ochkur

Jacobsen

Protheroe

et al. 2007

The Journal of Immunology

140

143

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Mouse models of allergen provocation and/or transgenic gene expression have provided significant insights regarding the cellular, molecular, and immune responses linked to the pathologies occurring as a result of allergic respiratory inflammation. Nonetheless, the inability to replicate the eosinophil activities occurring in patients with asthma has limited their usefulness to understand the larger role(s) of eosinophils in disease pathologies. These limitations have led us to develop an allergen-naive double transgenic mouse model that expresses IL-5 systemically from mature T cells and eotaxin-2 locally from lung epithelial cells. We show that these mice develop several pulmonary pathologies representative of severe asthma, including structural remodeling events such as epithelial desquamation and mucus hypersecretion leading to airway obstruction, subepithelial fibrosis, airway smooth muscle hyperplasia, and pathophysiological changes exemplified by exacerbated methacholine-induced airway hyperresponsiveness. More importantly, and similar to human patients, the pulmonary pathologies observed are accompanied by extensive eosinophil degranulation. Genetic ablation of all eosinophils from this double transgenic model abolished the induced pulmonary pathologies, demonstrating that these pathologies are a consequence of one or more eosinophil effector functions.

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“…TGF-␤ increases the expression of smooth muscle contractile proteins, such as smooth muscle ␣-actin and calponin, in airway smooth muscle and fibroblasts, and it increases airway smooth muscle cell size and number (77,78). TGF-␤ increases the expression of other growth factors, structural proteins, extracellular matrix proteins, and enzymes from airway smooth muscle cells (55). An interesting effect of TGF-␤ is the promotion of differentiation of fibroblasts into myofibroblasts secreting interstitial collagen and other growth factors, such as endothelin-1 and vascular endothelial growth factor.…”

Section: Tgf-␤mentioning

confidence: 99%

“…The airway smooth muscle cell not only has contractile properties but also is capable of expressing and releasing cytokines, chemokines, growth factors, and proteases (55,56), and can participate in the inflammatory and remodeling process (57). Airway smooth muscle cells also produce matrix proteins, and their behavior may depend on interactions with their own matrix (58).…”

Section: Airway Smooth Muscle In Airway Wall Remodeling Cytokines Andmentioning

confidence: 99%

“…Airway smooth muscle cells also produce matrix proteins, and their behavior may depend on interactions with their own matrix (58). Potential cytokines or chemokines of interest in COPD that may be released from airway smooth muscle include IL-6 and -8; monocyte chemotactic protein -1, -2, and -3; growthrelated oncogene-␣; CXCL10 (IP-10); and granulocyte-macrophage colony-stimulating factor (55,(59)(60)(61). Proinflammatory cytokines IL-1␤ and TNF-␣ and bradykinin induce the release of IL-8 (60, 62), a potent neutrophil chemoattractant and activator, whereas IFN-␥ and TNF-␣ induce the release of CXCL10, which is also expressed in airway smooth muscle cells of patients with COPD (59).…”

Section: Airway Smooth Muscle In Airway Wall Remodeling Cytokines Andmentioning

confidence: 99%

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The Role of Airway Smooth Muscle in the Pathogenesis of Airway Wall Remodeling in Chronic Obstructive Pulmonary Disease

Chung¹

2005

Proceedings of the American Thoracic Society

104

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Airway wall remodeling processes are present in the small airways of patients with chronic obstructive pulmonary disease, consisting of tissue repair and epithelial metaplasia that contribute to airway wall thickening and airflow obstruction. With increasing disease severity, there is also increased mucous metaplasia and submucosal gland hypertrophy, peribronchial fibrosis, and an increase in airway smooth muscle mass. Apart from its contractile properties, airway smooth muscle produces inflammatory cytokines, proteases, and growth factors, which may contribute to the remodeling process and induce phenotypic changes of the muscle. Airflow limitation responds minimally to ␤-agonists and corticosteroid therapy, unlike asthma, perhaps because of alterations in ␤-receptor or glucocorticoid receptor numbers, alterations in receptor signaling, or the constrictive limitation imposed by peribronchial fibrosis. Better response is observed with the combination of inhaled long-acting ␤-agonists and corticosteroids. This could result from effects at the level of airway smooth muscle. Airway wall remodeling may involve the release of growth factors from inflammatory or resident cells. The influence of smoking cessation or of current therapies on airway wall remodeling is unknown. Specific therapies for airway wall remodeling may be necessary, together with noninvasive methods of imaging small airway wall remodeling to assess responses.

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Effects of interleukin-1β, interleukin-13 and transforming growth factor-β on gene expression in human airway smooth muscle using gene microarrays

Cited by 51 publications

References 37 publications

Corticosteroid Inhibition of Growth-Related Oncogene Protein-α via Mitogen-Activated Kinase Phosphatase-1 in Airway Smooth Muscle Cells

Corticosteroid Inhibition of Growth-Related Oncogene Protein-α via Mitogen-Activated Kinase Phosphatase-1 in Airway Smooth Muscle Cells

Coexpression of IL-5 and Eotaxin-2 in Mice Creates an Eosinophil-Dependent Model of Respiratory Inflammation with Characteristics of Severe Asthma

The Role of Airway Smooth Muscle in the Pathogenesis of Airway Wall Remodeling in Chronic Obstructive Pulmonary Disease

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