Tag: inhibits

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Intranasal Curcumin Inhibits Pulmonary Fibrosis by Modulating Matrix Metalloproteinase-9 (MMP-9) in Ovalbumin-Induced Chronic Asthma.

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Intranasal Curcumin Inhibits Pulmonary Fibrosis by Modulating Matrix Metalloproteinase-9 (MMP-9) in Ovalbumin-Induced Chronic Asthma.

Inflammation. 2016 Nov 19;

Authors: Chauhan PS, Dash D, Singh R

Abstract
Pulmonary fibrosis is associated with irreversible, or partially reversible, airflow obstruction and ultimately unresponsiveness to asthma therapies such as corticosteroids. Intranasal curcumin, an anti-inflammatory molecule, has been found effective in allergic asthma. To study the effect of intranasal curcumin on airway remodeling and fibrosis in murine model of chronic asthma, BALB/c mice were sensitized to ovalbumin (OVA) and exposed to OVA aerosol (2%) from day 21 (after sensitization) for 5 weeks (twice/week). Curcumin (intranasal) was administered during the OVA aerosol challenge. Mice exposed to OVA developed inflammation dominated by eosinophils which lead to fibrosis and airway remodeling. Intranasal administration of curcumin significantly inhibited airway inflammation and pulmonary fibrosis, where MMP-9 activities were decreased along with ?-smooth muscle actin (?-SMA), MMP-9, TIMP-1, and eotaxin expressions. These results suggest that intranasal curcumin regulates airway inflammation and remodeling in chronic asthma.

PMID: 27866296 [PubMed – as supplied by publisher]

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The soluble guanylyl cyclase activator BAY 60-2770 inhibits murine allergic airways inflammation and human eosinophil chemotaxis.

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The soluble guanylyl cyclase activator BAY 60-2770 inhibits murine allergic airways inflammation and human eosinophil chemotaxis.

Pulm Pharmacol Ther. 2016 Nov 2;:

Authors: Baldissera L, Squebola-Cola DM, Calixto MC, Lima-Barbosa AP, Rennó AL, Anhê GF, Condino-Neto A, De Nucci G, Antunes E

Abstract
OBJECTIVES: Activators of soluble guanylyl cyclase (sGC) act preferentially in conditions of enzyme oxidation or haem group removal. This study was designed to investigate the effects of the sGC activator BAY 60-2770 in murine airways inflammation and human eosinophil chemotaxis.
METHODS: C57Bl/6 mice treated or not with BAY 60-2770 (1 mg/kg/day, 14 days) were intranasally challenged with ovalbumin (OVA). At 48 h, bronchoalveolar lavage fluid (BALF) was performed, and circulating blood, bone marrow and lungs were obtained. Human eosinophils purified from peripheral blood were used to evaluate the cell chemotaxis.
RESULTS: OVA-challenge promoted marked increases in eosinophil number in BAL, lung tissue, circulating blood and bone marrow, all of which were significantly reduced by BAY 60-2770. The IL-4 and IL-5 levels in BALF were significantly reduced by BAY 60-2770. Increased protein expression of iNOS, along with decreases of expression of sGC (?1 and ?1 subunits) and cGMP levels were detected in lung tissue of OVA-challenged mice. BAY 60-2770 fully restored to baseline the iNOS and sGC subunit expressions, and cGMP levels. In human isolated eosinophils, BAY 60-2770 (1-5 ?M) had no effects on the cGMP levels and eotaxin-induced chemotaxis; however, prior incubation with ODQ (10 ?M) markedly elevated the BAY 60-2770-induced cyclic GMP production, further inhibiting the eosinophil chemotaxis.
CONCLUSIONS: BAY 60-2770 reduces airway eosinophilic inflammation and rescue the sGC levels. In human eosinophils under oxidized conditions, BAY 60-2770 elevates the cGMP levels causing cell chemotaxis inhibition. BAY 60-2770 may reveal a novel therapeutic target for asthma treatment.

PMID: 27816773 [PubMed – as supplied by publisher]

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Apigenin inhibits TGF-?1-induced proliferation and migration of airway smooth muscle cells.

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Apigenin inhibits TGF-?1-induced proliferation and migration of airway smooth muscle cells.

Int J Clin Exp Pathol. 2015;8(10):12557-63

Authors: Li LH, Lu B, Wu HK, Zhang H, Yao FF

Abstract
It is well known that the proliferation and migration of ASM cells (ASMCs) plays an important role in the pathogenesis of airway remodeling in asthma. Previous studies reported that apigenin can inhibit airway remodeling in a mouse asthma model. However, its effects on the proliferation and migration of ASMCs in asthma remain unknown. Therefore, the aim of our present study was to investigate the effects of apigenin on ASMC proliferation and migration, and explore the possible molecular mechanism. We found that apigenin inhibited transforming growth factor-?1 (TGF-?1)-induced ASMC proliferation. The cell cycle was blocked at G1/S-interphase by apigenin. It also suppressed TGF-?1-induced ASMCs migration. Furthermore, apigenin inhibited TGF-?1-induced Smad 2 and Smad 3 phosphorylation in ASMCs. Taken together, these results suggested that apigenin inhibited the proliferation and migration of TGF-?1-stimulated ASMCs by inhibiting Smad signaling pathway. These data might provide useful information for treating asthma and show that apigenin has potential for attenuating airway remodeling.

PMID: 26722444 [PubMed – in process]

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Sonchus asper extract inhibits LPS-induced oxidative stress and pro-inflammatory cytokine production in RAW264.7 macrophages.

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Sonchus asper extract inhibits LPS-induced oxidative stress and pro-inflammatory cytokine production in RAW264.7 macrophages.

Nutr Res Pract. 2015 Dec;9(6):579-585

Authors: Wang L, Xu ML, Liu J, Wang Y, Hu JH, Wang MH

Abstract
BACKGROUND/OBJECTIVES: Sonchus asper is used extensively as an herbal anti-inflammatory for treatment of bronchitis, asthma, wounds, burns, and cough; however, further investigation is needed in order to understand the underlying mechanism. To determine its mechanism of action, we examined the effects of an ethyl acetate fraction (EAF) of S. asper on nitric oxide (NO) production and prostaglandin-E2 levels in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages.
MATERIALS/METHODS: An in vitro culture of RAW264.7 macrophages was treated with LPS to induce inflammation.
RESULTS: Treatment with EAF resulted in significant suppression of oxidative stress in RAW264.7 macrophages as demonstrated by increased endogenous superoxide dismutase (SOD) activity and intracellular glutathione levels, decreased generation of reactive oxygen species and lipid peroxidation, and restoration of the mitochondrial membrane potential. To confirm its anti-inflammatory effects, analysis of expression of inducible NO synthase, cyclooxygenase-2, tumor necrosis factor-?, and the anti-inflammatory cytokines IL-1? and IL-6 was performed using semi-quantitative RT-PCR. EAF treatment resulted in significantly reduced dose-dependent expression of all of these factors, and enhanced expression of the antioxidants MnSOD and heme oxygenase-1. In addition, HPLC fingerprint results suggest that rutin, caffeic acid, and quercetin may be the active ingredients in EAF.
CONCLUSIONS: Taken together, findings of this study imply that the anti-inflammatory effect of EAF on LPS-stimulated RAW264.7 cells is mediated by suppression of oxidative stress.

PMID: 26634045 [PubMed – as supplied by publisher]

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A simple molecule inhibits asthma-related inflammation at an early stage – Medical Xpress


Medical Xpress

A simple molecule inhibits asthma-related inflammation at an early stage
Medical Xpress
A promising new candidate for an asthma drug has been found: a simple synthetic molecule based on a sugar effectively inhibits the bronchial inflammation that arises with respiratory disease – moreover, at an earlier stage than the current, widely …

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RGS5 Inhibits Bronchial Smooth Muscle Contraction in Severe Asthma.

RGS5 Inhibits Bronchial Smooth Muscle Contraction in Severe Asthma.

Am J Respir Cell Mol Biol. 2012 Jan 26;

Authors: Yang Z, Balenga N, Cooper PR, Damera G, Edwards R, Brightling CE, Panettieri Jr RA, Druey KM

Abstract
Severe asthma is associated with fixed airway obstruction due to inflammation, copious luminal mucous, and increased airway smooth muscle (ASM) mass. Paradoxically, studies have demonstrated that hypertrophic and hyperplastic ASM characteristic of severe asthma has reduced contractile capacity. We compared GPCR-induced Ca(2+) mobilization and expression of GPCRs and signaling proteins related to procontractile signaling in ASM derived post-mortem from subjects who died of non-respiratory causes to cells from subjects who died of asthma. Despite increased or comparable expression of contraction-promoting GPCRs (bradykinin B2 or histamine H1 and PAR1, respectively) in asthmatic ASM cells relative to cells from healthy donors, asthmatic ASM cells had reduced histamine-induced Ca(2+) mobilization and comparable responses to bradykinin and thrombin, suggesting a post-receptor signaling defect. Accordingly, expression of Regulator of G protein signaling 5 (RGS5), an inhibitor of ASM contraction, was increased in cultured asthmatic ASM cells and in bronchial smooth muscle bundles of both asthmatic human subjects and allergen-challenged mice relative to those of healthy human subjects or naïve mice. Overexpression of RGS5 impaired Ca(2+)release to thrombin, histamine and carbachol and reduced contraction of precision-cut lung slices (PCLS) to carbachol. These results suggest that increased RGS5 expression contributes to decreased myocyte shortening in severe and/or fatal asthma.

PMID: 22281988 [PubMed – as supplied by publisher]

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Chlamydophila pneumonia inhibits the corticosteroid-induced suppressions of metalloproteinase-9 and tissue inhibitor metalloproteinase-1 secretion by human peripheral blood mononuclear cells.

Chlamydophila pneumonia inhibits the corticosteroid-induced suppressions of metalloproteinase-9 and tissue inhibitor metalloproteinase-1 secretion by human peripheral blood mononuclear cells.

J Med Microbiol. 2012 Jan 26;

Authors: Park CS, Lee YS, Kwon HS, Lee TH, Kim TB, Moon KA, Yoo B, Moon HB, Cho YS

Abstract
Chlamydophila pneumoniae infection has been suggested to be associated with severe asthma characterized by persistent airway limitation, which may be related to airway remodeling. We investigated whether C. pneumoniae infection affected the secretion of metalloproteinase-9 (MMP9) and tissue inhibitor metalloproteinase-1 (TIMP1), and altered the responsiveness of inflammatory cells to corticosteroids. Human peripheral blood mononuclear cells (PBMC) were cultured in vitro in the presence or absence of C. pneumoniae. Secretion of both MMP9 and TIMP1 was strongly suppressed by dexamethasone treatment in uninfected cells. MMP9 secretion was also significantly inhibited by dexamethasone in C. pneumoniae-infected cells, but TIMP1 secretion was not; hence the MMP9 to TIMP1 ratio decreased. Interestingly, expression of human glucocorticoid receptor (GR)?, which is believed to confer resistance to corticosteroids, was enhanced by dexamethasone treatment in C. pneumoniae-infected PBMC. We conclude that C. pneumoniae infection may promote airway remodeling by decreasing the ratio of MMP9 to TIMP1 secreted by inflammatory cells, and by altering cellular responsiveness to corticosteroids.

PMID: 22282461 [PubMed – as supplied by publisher]

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Amaranthus spinosus Linn. inhibits mast cell-mediated anaphylactic reactions.

Amaranthus spinosus Linn. inhibits mast cell-mediated anaphylactic reactions.

J Immunotoxicol. 2011 Dec 6;

Authors: Patil SD, Patel MR, Patel SR, Surana SJ

Abstract
The current study characterizes the mechanism by which the Amaranthus spinosus (Amaranthaceae) decreases mast cell-mediated anaphylactic reactions. Anaphylaxis is a typical hypersensitivity Type I reaction, sharing common mechanisms with asthma in its early and late phases. Mast cells are key as effector cells in hypersensitivity Type I reactions. A. spinosus has been traditionally used in the treatment of allergic bronchitis and asthma, but its role in mast cell-mediated anaphylactic reactions has not fully been investigated. This report investigated the potential effects of the ethyl acetate fraction of A. spinosus leaves (EAFAS) against a Compound 48/80 (potent secretagogue)-induced systemic anaphylactic shock paradigm in a mouse model. In addition, rat peritoneal mast cells (RPMC) were used in in vitro studies to investigate the effect of EAFAS on Compound 48/80-induced peritoneal mast cell degranulation and histamine release. When administration by the oral route-1?h before Compound 48/80 injection-EAFAS (at dose from 0.001-1?g/kg) completely inhibited the induced anaphylactic shock. EAFAS at concentrations ranging 0.25-1?mg/ml dose-dependently attenuated rates of mast cell degranulation and histamine release from RPMC that were evoked by Compound 48/80. The results of the present investigation indicated that EAFAS stabilizes the mast cell lipid bilayer membrane, thereby preventing the perturbation of membrane and the release of histamine. As a result of these anti-degranulating and anti-histaminic effects, it can be suggested that EAFAS may have a potential use in the prophylaxis and management of anaphylactic reactions.

PMID: 22145857 [PubMed – as supplied by publisher]

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