epidermal-growth-factor and Hypersensitivity

Decreased exposure to microbial agents in industrialized countries and urban living areas is considered as a risk factor of developing immune-mediated diseases, such as allergies and asthma. Epithelial surfaces in the gastrointestinal and respiratory tracts and in the skin constitute the primary areas in contact with the environmental microbial load.. We analyzed the levels of 30 cytokines and growth factors in serum or plasma as markers of the immune maturation in the participants in the DIABIMMUNE study from Russian Karelia (n = 60), Estonia (n = 83) and Finland (n = 89), three neighboring countries with remarkable differences in the incidences of allergies, asthma and autoimmune diseases.. We observed an upregulation of T helper cell signature cytokines during the first 12 months of life, reflecting natural development of adaptive immune responses. During the first years of life, circulating concentrations of epidermal growth factor (EGF) were significantly higher, especially in Russian children compared with Finnish children. The children who developed IgE sensitization showed lower levels of EGF than those without such responses.. Our results suggest that low circulating EGF levels associate with the risk of allergies possibly via the effects on the epithelial integrity and mucosal homeostasis.

Topics: Allergens; Asthma; Child; Child, Preschool; Epidermal Growth Factor; Humans; Hypersensitivity; Immunoglobulin E

Phosphoinositide 3-kinase (PI3K)/Akt pathway is linked to the development of asthma. Anti-malarial drug artesunate is a semi-synthetic derivative of artemisinin, the principal active component of a medicinal plant Artemisia annua, and has been shown to inhibit PI3K/Akt activity. We hypothesized that artesunate may attenuate allergic asthma via inhibition of the PI3K/Akt signaling pathway.. Female BALB/c mice sensitized and challenged with ovalbumin (OVA) developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Artesunate dose-dependently inhibited OVA-induced increases in total and eosinophil counts, IL-4, IL-5, IL-13 and eotaxin levels in bronchoalveolar lavage fluid. It attenuated OVA-induced lung tissue eosinophilia and airway mucus production, mRNA expression of E-selectin, IL-17, IL-33 and Muc5ac in lung tissues, and airway hyperresponsiveness to methacholine. In normal human bronchial epithelial cells, artesunate blocked epidermal growth factor-induced phosphorylation of Akt and its downstream substrates tuberin, p70S6 kinase and 4E-binding protein 1, and transactivation of NF-κB. Similarly, artesunate blocked the phosphorylation of Akt and its downstream substrates in lung tissues from OVA-challenged mice. Anti-inflammatory effect of artesunate was further confirmed in a house dust mite mouse asthma model.. Artesunate ameliorates experimental allergic airway inflammation probably via negative regulation of PI3K/Akt pathway and the downstream NF-κB activity. These findings provide a novel therapeutic value for artesunate in the treatment of allergic asthma.

Topics: Animals; Anti-Inflammatory Agents; Antimalarials; Artemisinins; Artesunate; Asthma; Bronchi; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Enzyme Activation; Epidermal Growth Factor; Epithelial Cells; Female; Gene Expression Regulation; Humans; Hypersensitivity; Mice; Mice, Inbred BALB C; Mucus; Ovalbumin; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Pyroglyphidae; Signal Transduction; Th2 Cells

To determine some early signs connected with the increased risk of future allergy development, gene expression and production of selected cytokines were tested in children of allergic mothers and compared with newborns of healthy mothers. Expression of IL-1β, IL-2, IL-4, IL-8, IL-10, IL-13, IFN-γ, TNF-α, TGF-β and EGF was tested in cord blood cells using real-time PCR and production of these cytokines was evaluated in cord sera by ELISA. Gene expression of IL-2, IL-4, IL-8, IFN-γ, IL-1β, TNF-α and TGF-β was decreased and that of IL-10, IL-13 and EGF increased in children of allergic mothers in comparison with those of healthy mothers. Significant differences in sera of healthy and allergic groups were only in IL-10 and EGF. Different relationship among serum cytokine levels reflects the fact that the cytokines are not produced only by blood cells. Significantly decreased production of EGF in newborns of allergic mothers could negatively influence maturation of mucosal membranes of these children and support thus their easier allergization. Allergic phenotype pointing to the bias to T(H)2 response and to possibly impaired intestine maturation was apparent already on the level of cord blood and could serve as a predictive sign of increased allergy risk.

Topics: Cytokines; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Fetal Blood; Gene Expression; Humans; Hypersensitivity; Infant, Newborn; Interleukin-10; Pregnancy; Reverse Transcriptase Polymerase Chain Reaction

Testing of cytokine levels in colostrum, cord blood and amniotic fluid of healthy and allergic mothers and their newborns (using protein microarrays and quantitative analysis by ELISA) revealed differences in the levels of IL-5, IL-10, TGF-beta, TNF-alpha, EGF and eotaxin between healthy and allergic groups. Significantly higher concentration of IL-5 and IL-10 in the colostrum of allergic mothers and cord blood of their children and also tendency to a higher level of IL-4 found at allergic mothers and their children (but without statistical significance) indicate a bias to T(H)2 response in this group. The higher level of TGF-beta in the colostrum of healthy mothers should be involved in beneficial immunological tuning of their children including enhanced IgA formation and better intestine maturation. In amniotic fluid, concentration of TGF-beta was higher in children of allergic mothers. A significantly higher level of EGF was proved in the colostrum of healthy mothers and in cord blood of their children in comparison with allergic group. EGF deficiency in the allergic group could impair or delay intestine maturation and support thus allergy development.

Topics: Amniotic Fluid; Colostrum; Cytokines; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Fetal Blood; Humans; Hypersensitivity; Infant, Newborn; Pregnancy; Prognosis; Protein Array Analysis; Risk Assessment

The concentrations of plasmin and epidermal growth factor were determined in tear fluid (TF) samples from wearers of different types of contact lenses (CLs) during and after cessation of CL wear (CLW). TF samples of 50 healthy eyes served as controls. The plasmin concentrations in the control group (0.4 +/- 0.1 microgram/ml; mean +/- SEM) were significantly lower (p less than 0.001) than in the group of soft CL (SCL) wearers during CLW (1.2 +/- 0.2 microgram/ml). Cessation of CLW led to a decrease in TF plasmin concentrations from 1.2 +/- 0.2 to 0.6 +/- 0.1 micrograms/ml in the group of SCL wearers (p less than 0.001), from 1.5 +/- 1.1 to 0.3 +/- 0.2 micrograms/ml in the group of extended-wear SCL wearers (p greater than 0.05) and from 0.4 +/- 0.3 to 0.0 +/- 0.0 microgram/ml in the group of gas-permeable CL wearers (p greater than 0.05). After CLW cessation, TF plasmin levels of CL wearers did not differ from those of controls. The occurrence of plasmin in TF was associated with a higher degree of corneal neovascularization and with the presence of limbal injection. The concentrations of epidermal growth factor in TF were not significantly altered by the discontinuation of CLW.

Topics: Conjunctiva; Contact Lenses, Extended-Wear; Contact Lenses, Hydrophilic; Epidermal Growth Factor; Fibrinolysin; Humans; Hypersensitivity; Prospective Studies; Tears; Wound Healing