Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate–induced asthma☆

Lee, Kyung S.; Jin, Sun; Kim, Seung S.; Lee, Yong C.

doi:10.1016/j.jaci.2004.03.008

Cited by 62 publications

(38 citation statements)

References 48 publications

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“…533, iss.1-3, pp. 133-144 Status: Postprint (Author's version) IL-4 levels in bronchoalveolar lavage fluids (Lee et al, 2004).…”

Section: Interactions Between Mmps and Cytokines -Growth Factors In Amentioning

confidence: 99%

“…The effect of doxycycline (a broad-spectrum MMP inhibitor) and other synthetic non-specific inhibitors on bronchial inflammation and airway hyperresponsiveness was evaluated by the use of a murine model for TDI-induced asthma. After oral administration of doxycycline, mice display a decreased airway inflammation, airway hyperresponsiveness, and a decreased expression of MMP-9 at mRNA and protein levels (Lee et al, 2001(Lee et al, , 2004. Other in vitro studies suggest that non-specific MMP inhibition by GM-6001 could lead to a decrease of goblet cell hyperplasia, one of the components of airway remodeling in asthma (Yoshisue and Hasegawa, 2004).…”

Section: New Therapeutic Insights In Asthmamentioning

confidence: 99%

“…Based on these observations, IL-4 might be considered as a potential link between inflammation and collagen deposition observed in asthmatic airways (Bergeron et al, 2003). It has been described that MMP inhibitors administered intratracheally in a mouse model of asthma can exert a direct effect on cytokines and are able to significantly abrogate the increased expression of cytokines, including IL-4 mRNA in lung tissues and IL-4 levels in bronchoalveolar lavage fluids (Lee et al, 2004).…”

Section: Interactions Between Mmps and Cytokines -Growth Factors In Amentioning

confidence: 99%

“…533, iss.1-3, pp. 133-144 Status: Postprint (Author's version) IL-4 levels in bronchoalveolar lavage fluids (Lee et al, 2004).IL-5 is another major Th 2 cytokine exerting an effect on eosinophils production, maturation, activation and acting as a strong chemotactic agent for those cells (Chung and Barnes, 1999). This cytokine could therefore significantly contribute to tissue damages observed in chronic asthma.…”

mentioning

confidence: 99%

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Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases

Guéders

Foidart

Noël

et al. 2006

European Journal of Pharmacology

279

224

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In healthy lung, Matrix Metalloproteinases (MMPs) and their physiological inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs), are produced in the respiratory tract by a panel of different structural cells. These activities are mandatory for many physiological processes including development, wound healing and cell trafficking. Deregulation of proteolytic-antiproteolytic network and inappropriate secretion of various MMPs by stimulated structural or inflammatory cells is thought to take part to pathophysiology of numerous lung diseases including asthma, chronic obstructive pulmonary disease (COPD), lung fibrosis and lung cancer. Cytokines and growth factors are involved in these inflammatory processes and some of those mediators interact directly with MMPs and TIMPs leading either to a regulation of their expression or changes in their biological activities by proteolytic cleavage. In turn, cytokines and growth factors modulate secretion of MMPs establishing a complex network of reciprocal interactions. Every MMP seem to play a rather specific role and some variations of their expression are observed in different lung diseases. The precise role of these enzymes and their inhibitors is now studied in depth as they could represent relevant therapeutic targets for many diseases. Indeed, MMP inhibition can lead either to a decrease of the intensity of a pathological process or, in the contrary for some of them, to an increase of disease severity. In this review, we focus on the role played by MMPs and TIMPs in asthma and we provide an overview of their potential roles in COPD, lung fibrosis and lung cancer, with a special emphasis on loops including MMPs and cytokines and growth factors relevant in these diseases.Keywords: Matrix metalloproteinase; Tissue inhibitor of MMP; Asthma; Cytokine; Growth factors Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs)Matrix metalloproteinases (MMPs), or matrixins, belong to the metzincin superfamily of metalloproteinases, also including astacins, ADAMs (a protein with a disintegrin and metallopro-tease domain) and ADAM-TS proteases (ADAM with a thrombospondin-like motif) (Sternlicht and Werb, 2001;Folgueras et al., 2004;Handsley and Edwards, 2005;Noel et al., 2004). MMPs are proteolytic enzymes believed to be implicated in many physiological and pathological processes including embryonic development, morphogenesis, reproductive processes, bone remodeling, wound healing, cancer, arthritis, atherosclerosis, MMPs are zinc and calciumdependent enzymes being able to degrade virtually all extracellular matrix components. This can modulate cell behaviour by creating influential cellular environment (Shapiro, 1998). The extracellular matrix is a complex network of molecules including collagens, fibronectin, laminin, entactin/ nidogen and heparan sulfate proteoglycans (Mott and Werb, 2004). The extracellular matrix is a mechanical support for cells but also acts as a reservoir for cytokines and growth factors (vascular endothelial ...

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“…533, iss.1-3, pp. 133-144 Status: Postprint (Author's version) IL-4 levels in bronchoalveolar lavage fluids (Lee et al, 2004).…”

Section: Interactions Between Mmps and Cytokines -Growth Factors In Amentioning

confidence: 99%

Section: New Therapeutic Insights In Asthmamentioning

confidence: 99%

Section: Interactions Between Mmps and Cytokines -Growth Factors In Amentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases

Guéders

Foidart

Noël

et al. 2006

European Journal of Pharmacology

279

224

View full text Add to dashboard Cite

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“…5C). Tetracyclines have been reported to reduce P-Akt levels in lung tissue in an animal model for asthma (57). Yet, it was also reported that minocycline enhanced P-Akt levels in retinal ganglion cells contributing to their increased survival (33).…”

Section: Discussionmentioning

confidence: 99%

Impact of Minocycline on Extracellular Matrix Metalloproteinase Inducer, a Factor Implicated in Multiple Sclerosis Immunopathogenesis

Hahn

Kaushik

Mishra

et al. 2016

The Journal of Immunology

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Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a transmembrane glycoprotein that is upregulated on leukocytes in active lesions in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Administration of anti-EMMPRIN Abs reduces the severity of EAE. Minocycline is a tetracycline antibiotic with immune-modulatory properties that decreases the severity of EAE; it was recently found to attenuate the conversion from a first demyelinating event to clinically definite MS in a phase III trial. We investigated whether and how minocycline affects the expression of EMMPRIN on T cells in culture and in mice afflicted with EAE. EMMPRIN expression in cultures of mouse splenocytes or human PBMCs was elevated upon polyclonal T cell activation, and this was reduced by minocycline correspondent with decreased P-Akt levels. An established MS medication, IFN-β, also diminished EMMPRIN levels on human cells whereas this was not readily observed for fingolimod or monomethylfumarate. In EAE-afflicted mice, minocycline treatment significantly reduced EMMPRIN levels on splenic lymphocytes at the presymptomatic (day 7) phase, and prevented the development of disease. Day 7 spleen transcripts from minocycline-treated EAE mice had a significantly lower MMP-9/TIMP-1 ratio, and significantly lower MCT-1 and CD98 levels, factors associated with EMMPRIN function. Day 16 (peak clinical severity) CNS samples from EAE mice had prominent representation of inflammatory perivascular cuffs, inflammatory molecules and EMMPRIN, and these were abrogated by minocycline. Overall, minocycline attenuated the activation-induced elevation of EMMPRIN on T cells in culture and in EAE mice, correspondent with reduced immune function and EAE CNS pathology.

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MMP induced by Gr‐1⁺ cells are crucial for recruitment of Th cells into the airways

et al. 2009

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Th2 lymphocytes deliver essential signals for induction of asthmatic airway inflammation. We previously found that airway antigen challenge induces recruitment of Gr-1 + neutrophils prior to the recruitment of Th2 cells. We examined, therefore, whether Gr-1 + cells contribute to the development of Th2-dependent airway inflammation. Systemic depletion of Gr-1 + cells using the RB6-8C5 monoclonal antibody reduced Th2 cell recruitment following i.n. antigen challenge. The levels of both MMP-9 and the tissue inhibitor of matrix metalloproteinases-1 mRNA were up-regulated in the lungs of mice 12 h after i.n. antigen challenge. Up-regulation of tissue inhibitor of matrix metalloproteinases-1 was independent of Gr-1 + cells, whereas up-regulation of MMP-9 RNA and total gelatinolytic activity was dramatically reduced in mice depleted of Gr-1 + cells. At 24 h after challenge, total lung collagenolytic activity was also up-regulated, in a Gr-1 + cell-dependent fashion.Systemic inhibition of MMP-8 and MMP-9 reduced the airway recruitment of Th cells, resulting in significantly reduced eosinophilic inflammation. These data suggest that antigen challenge via the airway activates Gr-1 + cells and consequently MMP to facilitate the recruitment of Th cells in the airway inflammatory response.Key words: Asthma . Airway inflammation . MMP . Tissue inhibitor of matrix metalloproteinases Supporting Information available online IntroductionAsthma is a complex disease, characterized by airway obstruction and bronchial hyperresponsiveness (AHR). Bronchial inflammation is a crucial component of asthma pathogenesis, and accumulating data suggest that asthma is due to an aberrant Th2 immune response to commonly inhaled antigens [1]. Despite the clear role of Th2 cells in this disease, little is known about the mechanisms that govern the recruitment of Th2 cells into airways.Although they are generally present in numbers lower than the numbers of mononuclear cells, polymorphonuclear neutrophils (PMN) also accumulate in the airways of patients with allergic and nonallergic asthma [2,3]. After allergen challenge of asthmatic patients or mice, PMN are the first inflammatory cells to accumulate within the airways [4][5][6], and the numbers of PMN recovered from the lungs of patients with allergic asthma by bronchoalveolar lavage (BAL) 4 h after allergen challenge have been calculated to be approximately 90-fold higher than the numbers of PMN recovered from the lungs of healthy controls [7]. 2281In mice, PMN are characterized by surface expression of the Gr-1 antigen [8]. Gr-1 is also expressed by plasmacytoid dendritic cells (pDC) [9,10], by a subset of monocytes/macrophages [11,12], and by immature eosinophils [13]. PMN and perhaps other Gr-1 + cells can be depleted from the circulation of mice by systemic treatment with the anti-Gr-1 monoclonal antibody (mAb), . Depletion of circulating Gr-1 + cells has been shown to reduce the severity of inflammatory diseases of the liver [15][16][17] and eye [15] by inhibition of effector T-cell recruit...

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Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate–induced asthma☆

Cited by 62 publications

References 48 publications

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases

Impact of Minocycline on Extracellular Matrix Metalloproteinase Inducer, a Factor Implicated in Multiple Sclerosis Immunopathogenesis

MMP induced by Gr‐1⁺ cells are crucial for recruitment of Th cells into the airways

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Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate–induced asthma☆

Cited by 62 publications

References 48 publications

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases

Impact of Minocycline on Extracellular Matrix Metalloproteinase Inducer, a Factor Implicated in Multiple Sclerosis Immunopathogenesis

MMP induced by Gr‐1+ cells are crucial for recruitment of Th cells into the airways

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MMP induced by Gr‐1⁺ cells are crucial for recruitment of Th cells into the airways