Increased circulating 92 kDa matrix metalloproteinase (MMP-9) activity in exacerbations of asthma

Oshita, Yuichi

doi:10.1136/thorax.58.9.757

Cited by 68 publications

(45 citation statements)

References 26 publications

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“…There is strong evidence of MMP-9 involvement in asthma, particularly in patients with severe asthma [39] and in acute, severe exacerbations [40]. MMP-9 is expressed by inflammatory cells and structural cells of the lungs, including the ASM cells.…”

Section: Discussionmentioning

confidence: 99%

Extracellular matrix components and regulators in the airway smooth muscle in asthma

Araujo

Dolhnikoff²,

Silva³

et al. 2008

Eur Respir J

205

180

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There is an intimate relationship between the extracellular matrix (ECM) and smooth muscle cells within the airways. Few studies have comprehensively assessed the composition of different ECM components and its regulators within the airway smooth muscle (ASM) in asthma.With the aid of image analysis, the fractional areas of total collagen and elastic fibres were quantified within the ASM of 35 subjects with fatal asthma (FA) and compared with 10 nonfatal asthma (NFA) patients and 22 nonasthmatic control cases. Expression of collagen I and III, fibronectin, versican, matrix metalloproteinase (MMP)-1, -2, -9 and -12 and tissue inhibitor of metalloproteinase-1 and -2 was quantified within the ASM in 22 FA and 10 control cases.In the large airways of FA cases, the fractional area of elastic fibres within the ASM was increased compared with NFA and controls. Similarly, fibronectin, MMP-9 and MMP-12 were increased within the ASM in large airways of FA cases compared with controls. Elastic fibres were increased in small airways in FA only in comparison with NFA cases.There is altered extracellular matrix composition and a degradative environment within the airway smooth muscle in fatal asthma patients, which may have important consequences for the mechanical and synthetic functions of airway smooth muscle. It has previously been demonstrated that ASM cells exposed to serum from patients with asthma produce increased levels of ECM proteins [6]. In turn, ECM proteins are able to affect the proliferative and secretory state of the ASM [7]. ASM cells secrete matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) [8], which have a role in the immunomodulatory mechanisms regulating ECM composition in asthma patients.In asthma patients, abnormal deposition of ECM elements has been described in the submucosal and adventitial areas of large and small airways [9][10][11][12]. The fractional area of the ECM has also been shown to be increased within the ASM layer in fatal asthma (FA) cases [13], but there are important reasons for better understanding of this subject. First, changes in the ECM composition within the ASM may affect its contractile properties. Digestion with collagenase of the ECM associated with ASM results in increased force generation and shortening in strips of ASM

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Section: Discussionmentioning

confidence: 99%

Extracellular matrix components and regulators in the airway smooth muscle in asthma

Araujo

Dolhnikoff²,

Silva³

et al. 2008

Eur Respir J

205

180

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“…Indeed, an increased MMP-9 activity has been reported in patients with allergic asthma. [31][32][33] Allergic bronchial asthma is characterized by upregulation of IgE and Th2 cytokine levels, infiltration of inflammatory cells such as macrophages, neutrophils and eosinophils, and airway hyperresponsiveness (AHR). It has also been reported that the gene expression of MMP-12 was upregulated in patients with asthma.…”

Section: Discussionmentioning

confidence: 99%

Increase in the Expression of Matrix Metalloproteinase-12 in the Airways of Rats with Allergic Bronchial Asthma

Chiba

Sakai

et al. 2007

Biological & Pharmaceutical Bulletin

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Matrix metalloproteinases (MMPs) are a family of proteinases which have zinc dependent structure centre, widely degrade extracellular matrix components and cleave non-matrix proteins including growth factors, chemoattractants and cell surface receptors.1) Most of the MMPs contain pro-domain which is accordant, through binding of the cysteine of pro-domain and histidines of the catalytic domain, to the metallo cation Zn 2ϩ . MMPs are activated by cleavage to set the catalytic domain free to act on substrates.MMP-12, which is also called metalloelastase and macrophage elastase, was firstly detected in mouse peritoneal macrophage.2) Subsequently, it was also found in alveolar macrophages, 3,4) bronchial epithelial cells 5) and airway smooth muscle cells. 6) Like other MMPs, MMP-12 consists of a pro-domain, a catalytic domain and a hemopexin domain, and is activated by taking off the pro-domain and then the hemopexin domain remaining the catalytic domain. It has been reported that the rat MMP-12 catalytic domain can degrade collagen-V and partially degrade collagen-I 7) and other extracellular matrix proteins. 8)Although the role of MMP-12 in airways is not fully understood, an involvement of MMP-12 has been reported in cigarette smoking-associated airway inflammatory diseases, such as chronic obstructive pulmonary disease (COPD). 9)MMP-12 has been reported to be associated with cigarette smoke-induced emphysema 10) and macrophage migration. 11)In patients with COPD, MMP-12-positive macrophages were increased in airway epithelial layers and bronchoalveolar lavage fluids when compared with normal subjects. 12) On the other hand, an upregulation of MMP-12 was also found in a mouse model of airway inflammation and remodeling induced by IL-13.13) Furthermore, an increased expression of MMP-12 was reported in a mouse model of allergic airway inflammation: the MMP-12 upregulation was not observed in IL-13-knockout mice.14) It is thus possible that MMP-12 is also relating to airway diseases mediated by Th2 cytokines such as allergic bronchial asthma. Indeed, MMP-12 has been proposed as one of the asthma candidate genes. 15) In the present study, the changes in the expression and localization of MMP-12 in airways of repeatedly antigen-challenged rats were investigated to reveal whether or not MMP-12 has relevance to allergic bronchial asthma. MATERIALS AND METHODS Sensitization and Antigenic ChallengeMale Wistar rats (6 weeks of age, specific pathogen-free, 170-190 g; Charles River Japan, Inc.) were sensitized and repeatedly challenged with 2,4-dinitrophenylated Ascaris suum antigen (DNP-Asc) by the method described in the previous papers. [16][17][18][19][20][21][22][23][24] In brief, the rats were sensitized with DNP-Asc together with Bordetella pertussis and were boosted 5 d later. Eight days after the first immunization, the rats were challenged by inhaling DNP-Asc for 40 min under conscious state. Then the animals were subjected to totally three times repeated antigen challenge every 48 h with the same inhalational cha...

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“…A significant increase in both the level of circulating MMP-9 [67] and its activity in BAL fluid [68] was also seen in patients after exacerbation compared with patients with asthma. Additionally, MMP-9 staining in the subepithelial basement membrane region was reportedly higher in severe asthmatic biopsies than in control subjects [69].…”

Section: Increased Deposition Of Extracellular Matrixmentioning

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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Increased circulating 92 kDa matrix metalloproteinase (MMP-9) activity in exacerbations of asthma

Cited by 68 publications

References 26 publications

Extracellular matrix components and regulators in the airway smooth muscle in asthma

Extracellular matrix components and regulators in the airway smooth muscle in asthma

Increase in the Expression of Matrix Metalloproteinase-12 in the Airways of Rats with Allergic Bronchial Asthma

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

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