curcumin and Airway-Remodeling

Bronchial epithelial cells and fibroblasts play an essential role in airway remodelling, due to their protective and secretory functions. There are many studies proving that infection caused by human rhinovirus may contribute to the process of airway remodelling. The beneficial properties of curcumin, the basic ingredient of turmeric, have been proved in many studies. Therefore, the aim of this study was the evaluation of curcumin immunomodulatory properties in development of airway remodelling. Fibroblasts (WI-38 and HFL1) and epithelial cells (NHBE) were incubated with curcumin. Additionally, remodelling conditions were induced with rhinovirus (HRV). Airway remodelling genes were determined by qPCR and immunoblotting. Moreover, NF-κB, c-Myc and STAT3 were silenced to analyse the pathways involved in airway remodelling. Curcumin reduced the expression of the genes analysed, especially MMP-9, TGF-β and collagen I. Moreover, curcumin inhibited the HRV-induced expression of MMP-9, TGF-β, collagen I and LTC4S (p < 0.05). NF-κB, c-Myc and STAT3 changed their course of expression. Concluding, our study shows that curcumin significantly downregulated gene expression related to the remodelling process, which is dependent on NF-κB and, partially, on c-Myc and STAT3. The results suggest that the remodelling process may be limited and possibly prevented, however this issue requires further research.

Topics: Airway Remodeling; Curcumin; Epithelial Cells; Fibroblasts; Humans; NF-kappa B

Bacterial infections can exacerbate asthmatic inflammation depending on lipopolysaccharide (LPS) composition, the outermost component of cell wall, its exposure timings as well as host's immune status. In present study, Balb/c mice were exposed to antigen (ovalbumin) and LPS simultaneously to establish an asthmatic model. Curcumin (diferuloylmethane), well known for its anti-inflammatory potential, was administered through intranasal route 1 h before LPS and OVA (ovalbumin) exposure to evaluate its efficacy against airway structural changes.. Inflammatory cell infiltration in lungs was measured by flow cytometry and further eosinophils were especially measured by immunofluorescence detection of major basic protein (MBP) as marker of eosinophilc granule protein. We also measured reactive oxygen species (ROS) in BALF by spectrofluorometry. MMP-9 activity was evaluated by gelatin zymography and mRNA expressions of MMP-9, TIMP-1, TGF-β1, IL-13, Collagen-1 and TLR-4 were measured in lungs. Protein expression of MAP kinases (P-ERK, P-JNK, P-p38), TLR-4, Cox-2, Lox-5 and Eotaxin was measured by western blotting. Hydroxyproline level and masson's trichrome staining were used to evaluate collagen deposition in lung.. Exposure to LPS (0.1 µg) exacerbates airway inflammation and induces structural changes in lungs by enhanced ROS production, collagen deposition, expression of genes involved in airway remodeling and activation of MAP kinases pathway enzymes. Intranasal curcumin pretreatment had significantly suppressed inflammatory mediators and airway remodeling proteins.. Our results strongly suggest that intranasal curcumin effectively protects LPS-induced airway inflammation and structural changes by modulating genes involved in airway remodeling in safer way; hence, it can be considered as supplementary alternative towards asthma treatments.

Topics: Administration, Intranasal; Airway Remodeling; Animals; Anti-Inflammatory Agents; Collagen; Curcumin; Disease Models, Animal; Inflammation; Lipopolysaccharides; Lung; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; Ovalbumin; Protective Agents; Toll-Like Receptor 4

The purpose of this study is to evaluate the therapeutic effects of curcumin on airway inflammation using LPS and cigarette smoke (LC)-induced COPD murine models and LPS-stimulated human bronchial epithelial (BEAS-2B) cells. In this research, COPD murine models were established after challenged with LPS for 2 days and exposed to cigarette smoke for 35 days. Treatment with curcumin for 10 days distinctly alleviated airway inflammation and airway remolding in LC-induced COPD mice according to the lung H&E histopathological examination. The number of neutrophils and lymphocytes in broncho alveolar lavage fluid (BALF) was significantly decreased in curcumin+LC-treated group compared with the LC-induced mice. Additionally, curcumin inhibited BEAS-2B cells proliferation, which suggested the preventive effect of curcumin on progressive airway remolding and inflammatory response mediated by bronchial epithelial cells. Further investigation demonstrated an underlying molecular mechanism for the therapeutic effects of curcumin may rely on the inhibition of the degradation of IκBα and COX-2 expression in curcumin+LC-treated COPD mice and LPS-stimulated BEAS-2B cells. Overall, curcumin alleviates the airway inflammation and airway remolding, which is closely related to inhibit the BEAS-2B cells proliferation and suppress the activation of NF-κB and COX-2 expression. These findings indicate that curcumin may be a potential agent for the therapy of COPD.

Topics: Airway Remodeling; Animals; Bronchi; Cell Line; Curcumin; Cyclooxygenase 2; Epithelial Cells; Humans; Inflammation; Mice; NF-kappa B; NF-KappaB Inhibitor alpha; Pulmonary Disease, Chronic Obstructive; Smoke; Tobacco Products

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 α-smooth muscle actin (α-SMA), MMP-9, TIMP-1, and eotaxin expressions. These results suggest that intranasal curcumin regulates airway inflammation and remodeling in chronic asthma.

Topics: Actins; Administration, Intranasal; Airway Remodeling; Animals; Asthma; Chronic Disease; Curcumin; Eosinophils; Inflammation; Matrix Metalloproteinase 9; Mice; Ovalbumin; Pulmonary Fibrosis; Tissue Inhibitor of Metalloproteinase-1

The inhibition of the proliferation of airway smooth muscle cells (ASMCs) is crucial for the prevention and treatment of asthma. Recent studies have revealed some important functions of curcumin; however, its effects on the proliferation of ASMCs in asthma remain unknown. Therefore, in this study, we performed in vitro and in vivo experiments to investigate the effects of curcumin on the proliferation of ASMCs in asthma. The thickness of the airway wall, the airway smooth muscle layer, the number of ASMCs and the expression of extracellular signal-regulated kinase (ERK) were significantly reduced in the curcumin-treated group as compared with the model group. Curcumin inhibited the cell proliferation induced by platelet-derived growth factor (PDGF) and decreased the PDGF-induced phosphorylation of ERK1/2 in the rat ASMCs. Moreover, the disruption of caveolae using methyl-β-cyclodextrin (MβCD) attenuated the anti-proliferative effects of curcumin in the ASMCs, which suggests that caveolin is involved in this process. Curcumin upregulated the mRNA and protein expression of caveolin-1. The data presented in this study demonstrate that the proliferation of ASMCs is inhibited by curcumin in vitro and in vivo; curcumin exerts these effects by upregulating the expression of caveolin-1 and blocking the activation of the ERK pathway.

Topics: Airway Remodeling; Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Bronchi; Caveolin 1; Cell Proliferation; Curcumin; Extracellular Signal-Regulated MAP Kinases; Female; Gene Expression Regulation; Lung; Mice; Myocytes, Smooth Muscle; Ovalbumin; Platelet-Derived Growth Factor; Primary Cell Culture; Protein Transport; Respiratory Hypersensitivity

To advance the control of airway epithelial cell function and asthma, we investigated the effects of a new curcumin derivative, CNB001, which possesses improved pharmacological properties. Normal human bronchial epithelial (NHBE) cells were stimulated with synthetic double-stranded RNA, Poly(I:C). CNB001 significantly suppressed IL-6, TNF-α, and GM-CSF production by NHBE cells, and did so more effectively than did curcumin or dexamethasone (DEX). CNB001 significantly inhibited the decrease of E-cadherin mRNA expression and increase of vimentin mRNA expression observed in NHBE cells induced by a combination of TGF-β1 and TNF-α, which are markers of airway remodeling. In NHBE cells stimulated by TGF-β1, CNB001 significantly downregulated the level of active serine peptidase inhibitor clade E member (SERPINE) 1, which is also reported to be related to airway remodeling. Whereas DEX alone significantly increased the active SERPINE1 level, the combination of DEX and CNB001 significantly suppressed active SERPINE1. In addition, CNB001 significantly suppressed neutrophil infiltration, IL-6, TNF-α, IL-13 and active SERPINE1 production in bronchoalveolar lavage fluid of the murine asthma model, which was not observed in the case of DEX. In conclusion, the curcumin derivative, CNB001, is a promising candidate to treat asthma associated with neutrophilic airway inflammation and remodeling.

Topics: Airway Remodeling; Animals; Asthma; Bronchi; Cadherins; Curcumin; Cytokines; Dexamethasone; Female; Glucocorticoids; Humans; Mice; Mice, Inbred BALB C; Plasminogen Activator Inhibitor 1; Pyrazoles; RNA, Double-Stranded