Eotaxin Production Research Articles

Anti-inflammatory effects of Zea mays L. husk extracts.

BackgroundZea mays L. (Z. mays) has been used for human consumption in the various forms of meal, cooking oil, thickener in sauces and puddings, sweetener in processed food and beverage products, bio-disel. However, especially, in case of husk extract of Z. mays, little is known about its anti-inflammatory effects. Therefore, in this study, the anti-inflammatory effects of Z. mays husk extract (ZMHE) and its mechanisms of action were investigated.MethodsThe husks of Z. Mays were harvested in kangwondo, Korea. To assess the anti-inflammatory activities of ZMHE, we examined effects of ZMHE on nitric oxide (NO) production, and release of soluble intercellular adhesion molecule-1 (sICAM-1) and eotaxin-1. The expression level of inducible nitric oxide synthase (iNOS) gene was also determined by Western blot and luciferase reporter assays. To determine its mechanisms of action, a luciferase reporter assay for nuclear factor kappa B (NF-kB) and activator protein-1 (AP-1) was introduced.ResultsZMHE inhibited lipopolysaccharide (LPS)-induced production of NO in RAW264.7 cells. In addition, expression of iNOS gene was reduced, as confirmed by Western blot and luciferase reporter assays. Effects of ZMHE on the AP-1 and NF-kB promoters were examined to elucidate the mechanism of its anti-inflammatory activity. Activation of AP-1 and NF-kB promoters induced by LPS was significantly reduced by ZMHE treatment. In addition, LPS-induced production of sICAM-1 and IL-4-induced production of eotaxin-1 were all reduced by ZMHE.ConclusionsOur results indicate that ZMHE has anti-inflammatory effects by downregulating the expression of iNOS gene and its downregulation is mediated by inhibiting NF-kB and AP-1 signaling.

The in vitro evaluation of isolated procyanidins as modulators of cytokine-induced eotaxin production in human alveolar epithelial cells

BACKGROUND: Populations that consume procyanidin-rich diets are less susceptible to inflammatory disease. Allergic asthma is an inflammatory lung disease perpetuated by a hyperreactive airway epithelium and eosinophil infiltration into the lung. Eotaxin-1 (CCL11) mediates eosinophil migration into tissues and its modulation could represent a means to assist the management of airway inflammation. OBJECTIVE: Here we evaluated procyanidins as a means of modulating CCL11 production in vitro. METHODS: We used human lung epithelial cells (A549) and optimized the conditions to induce CCL11 production in vitro. Cells were exposed to procyanidins for 6 h prior to an inflammatory insult of 5 ng/mL IL-4 with 5 ng/mL TNF for 48 h. An enzyme-linked immunosorbent assay was used to measure CCL11 production. RESULTS: Cells exposed to 5 M procyanidin A2 prior to the inflammatory challenge showed significantly inhibited (36%) CCL11 production. Under the same conditions, procyanidins B1 and B2 elicited no effect. Furthermore, combinations of procyanidins A2 and B2 (5 M total) demonstrated no evidence of a synergistic interaction. CONCLUSIONS: These data demonstrate that the regulation of CCL11 by lung epithelial cells is not ubiquitous among the three investigated procyanidins. We demonstrate a differential inhibition of CCL11 by A-type and B-type procyanidins. This evidence supports further studies into procyanidins, specifically A-type, for managing inappropriate airway inflammation.

Proton Pump Inhibitors (PPIs) May Modulate More Than Just Reflux in Chronic Rhinosinusitis with Nasal Polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently characterized by tissue eosinophilia but the relationship of eosinophilia to other type 2 biomarkers has not been explored. Furthermore, recent data suggesting PPIs modulate eotaxin-3 production in eosinophilic esophagitis may have therapeutic implications for CRSwNP. We sought to characterize levels of type 2 mediators and their relationship to tissue eosinophilia and radiographic severity in CRS. We further aimed to evaluate whether PPIs have therapeutic potential in CRS and identify possible mechanisms of action in airway epithelium. Type 2 mediators in nasal tissue and lavage fluid from control and CRS patients were measured by Luminex assay. Human sinonasal epithelial cells and BEAS-2B cells were stimulated with IL-13 in the presence and absence of PPIs. The effects of PPIs on IL-13-induced effects were measured by ELISA, qRT-PCR, and pH imaging. IL-13, eotaxin-2 and eotaxin-3 were highly elevated in CRSwNP compared to control and were correlated with tissue ECP and radiographic severity. CRS patients taking PPIs had significantly lower tissue eotaxin-2 and eotaxin-3 levels than those not taking PPIs. In vitro, 5 different PPIs and the competitive H+/K+-ATPase inhibitor SCH-28080 all significantly inhibited IL-13-induced eotaxin-3 release by airway epithelial cells. In addition, IL-13-induced eotaxin-3 expression was dependent on the presence of extracellular K+ and associated with a PPI sensitive efflux of H+ions. IL-13, eotaxin-2, and eotaxin-3 in tissue are potential biomarkers of eosinophilia and severity in CRSwNP. Inhibition of IL-13-induced eotaxin-3 by PPIs may provide therapeutic benefit in CRSwNP via a novel H+/K+-dependent mechanism.

Microfibrillar-associated protein 4 modulates airway smooth muscle cell phenotype in experimental asthma

BackgroundRecently, several proteins of the extracellular matrix have been characterised as active contributors to allergic airway disease. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein abundant in the lung,...

Combination effects of Gumiganghwal-tang water extract and montelukast on airway inflammation in human bronchial epithelial cells

Purpose: Gumiganghwal-tang (known as Kumi-Kyokatsuto in Japanese) is well known traditional herbal prescription, which consists of 12 different herbs; Osterici Radix, Saposhnikoviae Radix, Cnidii Rhizoma, Angelicae Dahuricae Radix, Atractylodis Rhizoma, Scutellariae Radix, Rehmanniae Radix, Asari Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma Recens, Zizyphi Fructus, and Allii Fistulosi Bulbus. Gumiganghwal-tang has been commonly used in various disease including common cold, pain, and inflammatory diseases in Korea. Montelukast has been used as an effective therapeutic agent for prevention and treatment of allergic rhinitis or asthma. The objective of this study is to find out the combination effect on interaction of Gumiganghwaltang water extract (GGTW) and montelukast using human bronchial epithelial, BEAS-2B cells. Methods:Anti-inflammation effects were selected to study the effects on IL-4/TNF-induced inflammatory response in BEAS2B cells. Cell supernatants and mRNA were collected for cellular inflammatory mediators determined via enzymelinked immunosorbent assay, gelatin zymography, and polymerase chain reaction. Results: After treatment of IL-4/TNF, the production of eotaxin, regulated on activation of normal T-cell-expressedandsecreted (RANTES), matrix metalloproteinases-9 (MMP9), and vascular cell adhesion molecule (VCAM)-1 expression were increased. However, each of GGTW and montelukast was significantly inhibit the production of eotaxin, RANTES, MMP-9, andVCAM-1 expression.Moreover, drug combinations (co-treatment ofGGTWwithmontelukast)weremore effective than each treatment, although the difference was not significant. Conclusion: Taken together, these findings suggest that GGTW combined with montelukast may be useful to reduce airway inflammation, which may explain its beneficial effect for the regulation of inflammatory disease. Contact: Woo-Young Jeon, ssamggun85@kiom.re.kr

Anti-allergic properties of curine, a bisbenzylisoquinoline alkaloid.

Curine is a bisbenzylisoquinoline alkaloid isolated from Chondrodendron platyphyllum (Menispermaceae). Recent findings have shed light on the actions of curine in different models of allergy and inflammation. Here we review the properties and mechanisms of action of curine focusing on its anti-allergic effects. Curine pre-treatment significantly inhibited the scratching behavior, paw edema and systemic anaphylaxis induced by either ovalbumin (OVA) in sensitized animals or compound 48/80, through mechanisms of mast cell stabilization and inhibition of mast cell activation to generate lipid mediators. In addition, oral administration of curine significantly inhibited eosinophil recruitment and activation, as well as, OVA-induced airway hyper-responsiveness in a mouse model of asthma, through inhibition of the production of IL-13 and eotaxin, and of Ca2+ influx. In conclusion, curine exhibit anti-allergic effects in models of lung, skin and systemic allergy in the absence of significant toxicity, and as such has the potential for anti-allergic drug development.

Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) was historically distinguished from gastroesophageal reflux disease on the basis of histology and lack of responsiveness to acid suppressive therapy, but it is now appreciated that esophageal eosinophilia can respond to proton pump inhibitors. Genetic and environmental factors contribute to risk for EoE, particularly early-life events. Disease pathogenesis involves activation of epithelial inflammatory pathways (production of eotaxin-3 [encoded by CCL26]), impaired barrier function (mediated by loss of desmoglein-1), increased production and/or activity of transforming growth factor-β, and induction of allergic inflammation by eosinophils and mast cells. Susceptibility has been associated with variants at 5q22 (TSLP) and 2p23 (CAPN14), indicating roles for allergic sensitization and esophageal specific protease pathways. We propose that EoE is a unique disease characterized by food hypersensitivity; strong hereditability influenced by early-life exposures and esophageal-specific genetic risk variants; and allergic inflammation and that the disease is remitted by disrupting inflammatory and T-helper type 2 cytokine-mediated responses and through dietary elimination therapy.

Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced Th2 responses and airway inflammation in mice.

Zerumbone is a sesquiterpene compound isolated from the rhizome of wild ginger, Zingiber zerumbet Smith. The rhizomes of the plant are used as a spice and traditional medicine. Zerumbone was shown to possess anticarcinogenic, anti-inflammatory, and antioxidant properties. However, the antiallergic activity and the underlying mechanism of zerumbone have not been reported. Herein, we investigated the immunomodulatory effects of zerumbone on antigen-presenting dendritic cells (DCs) in vitro and its potential therapeutic effects against ovalbumin (OVA)-induced T helper 2 (Th2)-mediated asthma in mice. In the presence of zerumbone, lipopolysaccharide-activated bone marrow-derived DCs enhanced T cell proliferation and Th1 cell polarization in an allogeneic mixed lymphocyte reaction. In animal experiments, mice were sensitized and challenged with OVA, and were orally treated with different doses of zerumbone after sensitization. Circulating titers of OVA-specific antibodies, airway hyperresponsiveness to methacholine, histological changes in lung tissues, the cell composition and cytokine levels in bronchoalveolar lavage fluid, and cytokine profiles of spleen cells were assessed. Compared to OVA-induced hallmarks of asthma, oral administration of zerumbone induced lower OVA-specific immunoglobulin E (IgE) and higher IgG2a antibody production, attenuated airway hyperresponsiveness, prevented eosinophilic pulmonary infiltration, and ameliorated mucus hypersecretion. Zerumbone treatment also reduced the production of eotaxin, keratinocyte-derived chemokine (KC), interleukin (IL)-4, IL-5, IL-10, and IL-13, and promoted Th1 cytokine interferon (IFN)-γ production in asthmatic mice. Taken together, these results suggest that zerumbone exhibits an antiallergic effect via modulation of Th1/Th2 cytokines in an asthmatic mouse model.

Ferulic Acid Induces Th1 Responses by Modulating the Function of Dendritic Cells and Ameliorates Th2-Mediated Allergic Airway Inflammation in Mice.

This study investigated the immunomodulatory effects of ferulic acid (FA) on antigen-presenting dendritic cells (DCs) in vitro and its antiallergic effects against ovalbumin- (OVA-) induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS) stimulation induced a high level of interleukin- (IL-) 12 but reduced the expression levels of the proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor- (TNF-) α. Compared to control-treated DCs, FA significantly enhanced the expressions of Notch ligand Delta-like 4 (Dll4), MHC class II, and CD40 molecules by these DCs. Furthermore, these FA-treated DCs enhanced T-cell proliferation and Th1 cell polarization. In animal experiments, oral administration of FA reduced the levels of OVA-specific immunoglobulin E (IgE) and IgG1 and enhanced IgG2a antibody production in serum. It also ameliorated airway hyperresponsiveness and attenuated eosinophilic pulmonary infiltration in dose-dependent manners. In addition, FA treatment inhibited the production of eotaxin, Th2 cytokines (IL-4, IL-5, and IL-13), and proinflammatory cytokines but promoted the Th1 cytokine interferon- (IFN-) γ production in bronchoalveolar lavage fluid (BALF) and the culture supernatant of spleen cells. These findings suggest that FA exhibits an antiallergic effect via restoring Th1/Th2 imbalance by modulating DCs function in an asthmatic mouse model.

Inhibitory activity of Socheongryong-tang and its constituent components against the production of RANTES, eotaxin, eotaxin-3 and MMP-9 from BEAS-2B cells

Socheongryeong‑tang (SCRT) is a herbal formula previously used to treat pulmonary diseases primarily caused by the common cold virus, including airway inflammation, asthma and allergy. The aim of the present study was to investigate the inhibitory effect of SCRT water extract and its 13 constituent components on chemokine and enzyme production in the human bronchial epithelium cell line BEAS‑2B when induced by tumor necrosis factor‑α and interleukin‑4. The chemokines examined included regulated on activation of normal T‑cell‑expressed‑and‑secreted (RANTES), eotaxin and eotaxin‑3. The SCRT water extract demonstrated a dose‑dependent inhibition of RANTES, eotaxin, eotaxin‑3 and matrix metalloproteinase‑9 (MMP‑9) in BEAS‑2B cells. The 13 constituent compounds of SCRT water extract were quantitatively determined, and it was found that gallic acid, 6‑gingerol and methyl eugenol produced the most potent inhibition of RANTES, eotaxin and eotaxin‑3 as well as MMP‑9 activity regardless of their concentration in SCRT water extract. Principal component analysis and hierarchical clustering analysis revealed that the inhibitory effect of these three compounds contributed to that of SCRT water extract. In conclusion, the results of the present study indicated that the inhibitory effects of SCRT on chemokine and enzyme production in BEAS‑2B cells was associated with three of its constituent compounds, gallic acid, 6‑gingerol and methyl eugenol. This therefore suggested the potential use of these compounds as anti‑inflammatory agents.

CYTOKINES AND CHEMOKINES IN THE BLOOD PLASMA OF PATIENTS WITH CHRONIC HEPATITIS C

Abstract. Pathogenesis of chronic hepatitis C (CHC) remains to be determined. Mechanisms of liver parenchyma damage in patients with CHC are complex and different. Cytokines play the role of intermediaries in the process of fibrosis development and chronic inflammation. In the present study levels of 27 cytokines in the blood plasma of 14 patients with CHC were tested using multiplex analysis. The liver biopsy was performed in all patients to define the activity of inflammation (histological activity index) and the degree of fibrosis. Nineteen samples of blood plasma obtained from healthy individuals were served as a control group in this study. The following cytokines were measured: IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, eotaxin, FGF-2, G-CSF, GM-CSF, IFNγ, IP-10, MCP-1, MIP-1α, MIP-1β, RANTES, PDGF-BB, TNFα and VEGF. In patients with CHC elevated levels of plasma IL-1ra, IL-6, IL-7, IFNγ, IL-12 (p70), IL-4, IL-9, IL-8, IP-10, eotaxin, MCP-1, MIP-1β, TNFα, G-CSF and GM-CSF were found in compare with the control group. At the same time levels of FGF-2 and PDGF-BB were reduced in patients with CHC in compare with controls. Differences in the production of IL-1ra, IL-6, IL-7, IFNγ, IL-12 (p70), IL-4, IL-9, IL-8, IP-10, eotaxin, MCP-1, MIP-1β, TNFα, G-CSF and GM-CSF were depend on the genotype of HCV (3a or 1b), histological activity index in liver tissue and the degree of liver fibrosis. The revealed changes of cytokine production in patients with CHC characterize different orientation of regulatory violations confirming that CHC is an immunopathological process.

Plant-derived Foods for the Attenuation of Allergic Airway Inflammation

Asthma is an allergy-mediated inflammatory disease characterised by infiltration of the airway with mast cells, lymphocytes, and eosinophils. The disease is induced by co-ordination of T-helper cell type 2 (Th2) cytokines and inflammatory signal molecules. Fruits and vegetables are a rich source of polyphenolic bioactive compounds, which have been observed to have health-promoting properties when consumed by humans. In particular, fruit-derived proanthocyanins and anthocyanins have been found to attenuate lung inflammation. Epidemiological studies have revealed correlations between fruit consumption and a lower prevalence of respiratory symptoms and lower incidence of non-specific lung diseases. In this review we summarise the current understanding of the pathophysiologic mechanism(s) involved in the development of allergic airway disease. We also review evidence of the beneficial effects of plant-derived foods, their components and metabolites in allergic airway inflammation arising from in vitro and rodent studies, epidemiological studies and human intervention trials. The mechanism, biological relevance and functional benefits, such as immune modulation (e.g. reduction in cytokine and eotaxin production), antioxidant ability, tissue remodelling and tight junction function are also discussed.

Demethylation of the Human Eotaxin-3 Gene Promoter Leads to the Elevated Expression of Eotaxin-3

DNA demethylation has been primarily studied in the context of development biology, cell fate, and cancer, with less attention on inflammation. In this article, we investigate the association between DNA methylation and production of the chemoattractant cytokine eotaxin-3 in the tissue of patients with allergic disease. Regions of the human eotaxin-3 promoter were found to be hypomethylated in primary epithelial cells obtained from allergic tissue compared with normal control tissue. The demethylation of a specific CpG site (designated CpG 2), which is juxtaposed to a key cAMP-responsive element site, was significantly demethylated in patient-derived compared with normal control tissue-derived epithelial cells. Levels of methylation at CpG 2 inversely correlated with basal and IL-13-induced eotaxin-3 gene expression. Conversely, global inhibition of methylation with 5-azacytidine promoted eotaxin-3 production in association with decreasing CpG 2 methylation. In addition, the basal and IL-13-induced eotaxin-3 transcriptional activity was suppressed by promoter methylation using a methylation-free in vitro system. Furthermore, EMSAs demonstrated that the attachment of CREB binding protein and activating transcription factor 2 (ATF-2) to the cAMP-responsive element site was methylation dependent. Taken together, these data identify a contributory role for DNA methylation in regulating eotaxin-3 production in human allergic inflammation.

Matrine attenuates allergic airway inflammation and eosinophil infiltration by suppressing eotaxin and Th2 cytokine production in asthmatic mice

Ethnopharmacological relevanceMatrine has been isolated from Sophora flavescens, and found to show anti-inflammatory effects in macrophages and anti-cachectic effects in hepatomas. The present study investigated whether matrine suppressed eosinophil infiltration and airway hyperresponsiveness (AHR) in mice, and decreased the inflammatory response of tracheal epithelial cells. Materials and methodsBALB/c mice were sensitized and challenged with ovalbumin to induce allergic asthma in mice. These asthmatic mice were given various doses of matrine by intraperitoneal injection. Additionally, activated human tracheal epithelial cells (BEAS-2B cells) were treated with matrine, and evaluated for levels of proinflammatory cytokines and chemokines. ResultsWe found that matrine significantly decreased AHR, and suppressed goblet cell hyperplasia, eosinophil infiltration, and inflammatory response in the lung tissue of asthmatic mice. Matrine also reduced the levels of Th2 cytokines and chemokines in bronchoalveolar lavage fluid, and suppressed OVA–IgE production in serum. Furthermore, matrine treatment of activated BEAS-2B cells decreased production of proinflammatory cytokines and eotaxins, as well as suppressed ICAM-1 expression and thus adhesion of eosinophils to inflammatory BEAS-2B cells in vitro. ConclusionsOur findings suggest that matrine can improve allergic asthma in mice, and therefore has potential therapeutic potential in humans.

Reduction of eotaxin production and eosinophil recruitment by pulmonary autologous macrophage transfer in a cockroach allergen-induced asthma model

We sought to investigate the effects of cockroach allergen (CRA) exposure on the lung macrophage population to determine how different macrophage phenotypes influence exacerbation of disease. CRA exposure caused significantly reduced expression of CD86 on lung macrophages. These effects were not systemic, as peritoneal macrophage CD86 expression was not altered. To investigate whether naïve macrophages could reduce asthma-like pulmonary inflammation, autologous peritoneal macrophages were instilled into the airways 24 h before the final CRA challenge. Pulmonary inflammation was assessed by measurement of airway hyperresponsiveness, mucin production, inflammatory cell recruitment, and cytokine production. Cell transfer did not have significant effects in control mice, nor did it affect pulmonary mucin production or airway hyperresponsiveness in control or CRA-exposed mice. However, there was significant reduction in the number of eosinophils recovered in the bronchoalveolar lavage (BAL) (5.8 × 10⁵ vs. 0.88 × 10⁵), and total cell recruitment to the airways of CRA-exposed mice was markedly reduced (1.1 × 10⁶ vs. 0.57 × 10⁶). The reduced eosinophil recruitment was reflected by substantially lower levels of eosinophil peroxidase in the lung and significantly lower concentrations of eotaxins in BAL (eotaxin 1: 3 pg/ml vs. undetectable; eotaxin 2: 2,383 vs. 131 pg/ml) and lung homogenate (eotaxin 1: 1,043 vs. 218 pg/ml; eotaxin 2: 10 vs. 1.5 ng/ml). We conclude that CRA decreases lung macrophage CD86 expression. Furthermore, supplementation of the lung cell population with peritoneal macrophages inhibits eosinophil recruitment, achieved through reduction of eotaxin production. These data demonstrate that transfer of naïve macrophages will reduce some aspects of asthma-like pulmonary inflammation in response to CRA.

Alendronate Attenuates Eosinophilic Airway Inflammation Associated with Suppression of Th2 Cytokines, Th17 Cytokines, and Eotaxin-2

Bisphosphonates (BPs) have been widely used to treat osteoporosis. They act by inhibiting farnesyl diphosphate synthase in the mevalonate pathway. This resembles the action of statins, whose immune-modulating effect has recently been highlighted. In contrast, the effect of BPs on immune responses has not been elucidated well. In this study, we examined the effect of alendronate (ALN), a nitrogen-containing BP, on allergic airway inflammation in a mouse model. BALB/c mice were sensitized twice with OVA and challenged three times with nebulized OVA to induce eosinophilic airway inflammation. ALN was administered by an intragastric tube before each inhalation. ALN strongly suppressed airway eosinophilia and Th2, as well as Th17 cytokine production in the lung. ALN also attenuated eotaxin-2 production in the lung. Immunohistochemistry demonstrated that the major cell source of eotaxin-2 was peribronchial/perivascular macrophages, and flow cytometrical studies confirmed that ALN decreased eotaxin-2 expression in these macrophages. Furthermore, ALN attenuated eotaxin-2 production from mouse pleural macrophages and human monocyte/macrophage-like THP-1 cells in vitro. These results suggest that ALN suppressed Ag-induced airway responses in the mouse model. The suppression of eotaxin-2 production from macrophages appears to be one of ALN's immunomodulatory effects, whereas the mechanism by which ALN suppressed Th2 and Th17 responses could not be fully elucidated in this study. Although a clinical study should be conducted, ALN could be a novel therapeutic option for asthma.

Type 2 innate lymphoid cells control eosinophil homeostasis

Eosinophils are specialized myeloid cells associated with allergy and helminth infections. Blood eosinophils demonstrate circadian cycling, as described over 80 years ago,1 and are abundant in the healthy gastrointestinal tract. Although a cytokine, interleukin (IL)-5, and chemokines such as eotaxins, mediate eosinophil development and survival,2 and tissue recruitment,3 respectively, the processes underlying the basal regulation of these signals remain unknown. Here, we show that serum IL-5 is maintained by long-lived type 2 innate lymphoid cells (ILC2) resident in peripheral tissues. ILC2 secrete IL-5 constitutively and are induced to co-express IL-13 during type 2 inflammation, resulting in localized eotaxin production and eosinophil accumulation. In the small intestine where eosinophils and eotaxin are constitutive,4 ILC2 co-express IL-5 and IL-13, which is enhanced after caloric intake. The circadian synchronizer vasoactive intestinal peptide (VIP) also stimulates ILC2 through the VPAC2 receptor to release IL-5, linking eosinophil levels with metabolic cycling. Tissue ILC2 regulate basal eosinophilopoiesis and tissue eosinophil accumulation through constitutive and stimulated cytokine expression, and this dissociated regulation can be tuned by nutrient intake and central circadian rhythms.

Effects of n‐3 PUFA on the CD4+ type 2 helper T‐cell‐mediated immune responses in Fat‐1 mice

It has been suggested that n-3 PUFA can be used as a preventive or therapeutic strategy to control allergic asthma. But little is known about the exact mechanisms by which n-3 PUFA modulates it. Here, the effects of elevated n-3 PUFA on ovalbumin (OVA) induced airway inflammation were investigated using Fat-1 transgenic mice that can convert n-6 PUFA to n-3 PUFA endogenously. First, we tested whether Fat-1 expression modulates CD4⁺ T-cell activation, proliferation, and differentiation in vitro and found that the Fat-1 expression attenuated all of these CD4⁺ T-cell responses by suppression of T-cell receptor mediated signaling and cytokine-mediated phosphorylation of STATs. When the Fat-1 mice were sensitized and challenged with the OVA, they showed a significant decrease in the recruitment of inflammatory cells into airway, the production of Th2 cytokines, eotaxin, and mucin in the lung, and the concentration of OVA-specific IgE in the serum. Furthermore, the differentiation of CD4⁺ T cells into Th2 was also decreased in the spleen of Fat-1 mice. Our results showed that an elevated level of n-3 PUFA was effective in preventing allergic airway inflammation by modulating the activation and differentiation of CD4⁺ T cells in Fat-1 mice.

사과 '히로사키' 캘러스 추출물의 기능성 화장품 소재로서의 특성

In order to investigate functional characterization of callus extracts of apple 'Hirosaki' for cosmetic materials, biological activities of its extracts including wrinkle improvement, hair growth, and anti-inflammatory effect were investigated. The callus extract showed similar activity with TGF-<TEX>${\beta}$</TEX> used as positive control at 50 <TEX>${\mu}g/mL$</TEX> in the test of collagen synthesis, and increased 40% of proliferation of hair follicle dermal papilla cells. Especially, in case of anti-inflammatory effect, callus extract inhibited about 50% of COX-2 expression which was known as response for intermediating inflammation, and about 70% of eotaxin-1 production which was increased by atopy dermatitis.

Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca++ influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs.