ABSTRACT
In intestinal helminth infections, Th2 immune respones are generally associated with mucin secretion for worm expulsion from the host intestine. In particular, IL-4 and IL-13 are the important cytokines related with intestinal mucus production via STAT6 signalling in nematode infections. However, this perspective has never been studied in Gymnophalloides seoi infection. The present study aimed to observe the STAT6 signalling and cytokine responses in C57BL/6 mice, a mouse strain resistant to infection with this trematode. The results showed that worm expulsion occurred actively during days 1-2 post-infection (PI), when goblet cells began to proliferate in the small intestine. The STAT6 gene expression in the mouse spleen became remarkable from day 2 PI. Moreover, G. seoi infection induced a significant increase of IL-13 from day 4 PI in the spleen of infected mice. Our results suggested that goblet cell hyperplasia and worm expulsion in G. seoi-infected mice should be induced by STAT6 signalling, in which IL-13 may be involved as a dominant triggering cytokine.
Subject(s)
Animals , Female , Mice , Crassostrea , Goblet Cells/pathology , Hyperplasia/pathology , Interleukin-13/metabolism , Interleukin-4/metabolism , Intestine, Small/immunology , Metacercariae , Mice, Inbred C57BL , STAT6 Transcription Factor/metabolism , Signal Transduction , Specific Pathogen-Free Organisms , Spleen/immunology , Trematoda/immunology , Trichinellosis/immunologyABSTRACT
PURPOSE: Cockroach (CR) is an important inhalant allergen and can induce allergic asthma. However, the mechanism by which CR induces airway allergic inflammation and the role of endotoxin in CR extract are not clearly understood in regards to the development of airway inflammation. In this study, we evaluated whether endotoxin is essential to the development of CR induced airway allergic inflammation in mice. MATERIALS AND METHODS: Airway allergic inflammation was induced by intranasal administration of either CR extract, CR with additional endotoxin, or endotoxin depleted CR extract, respectively, in BALB/c wild type mice. CR induced inflammation was also evaluated with toll like receptor-4 (TLR-4) mutant (C3H/HeJ) and wild type (C3H/HeN) mice. RESULTS: Intranasal administration of CR extracts significantly induced airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation, as well as goblet cell hyperplasia in a dose-dependent manner. The addition of endotoxin along with CR allergen attenuated eosinophilic inflammation, interleukin (IL)-13 level, and goblet cell hyperplasia of respiratory epithelium; however, it did not affect the development of AHR. Endotoxin depletion in CR extract did not attenuate eosinophilic inflammation and lymphocytosis in BAL fluid, AHR and IL-13 expression in the lungs compared to CR alone. The attenuation of AHR, eosinophilic inflammation, and goblet cell hyperplasia induced by CR extract alone was not different between TLR-4 mutant and the wild type mice. In addition, heat inactivated CR extract administration induced attenuated AHR and eosinophilic inflammation. CONCLUSION: Endotoxin in CR extracts may not be essential to the development of airway inflammation.
Subject(s)
Animals , Female , Mice , Allergens/immunology , Asthma/chemically induced , Cockroaches/immunology , Endotoxins/immunology , Enzyme-Linked Immunosorbent Assay , Inflammation/chemically induced , Interferon-gamma/metabolism , Interleukin-13/metabolism , Interleukin-5/metabolism , Mice, Inbred BALB C , Respiratory Hypersensitivity/chemically inducedABSTRACT
Since the risk of developing allergic disease increases in individuals exposed to allergens previously, even during the neonatal period, the immunologic status of a fetus may be important in the subsequent development of allergy. We evaluated the fetal factors to predict atopic dermatitis (AD) at 12 months in 412 infants of a COhort for Childhood Origin of Asthma and Allergic Diseases (COCOA) in the general Korean population. Cord blood mononuclear cells (CBMCs) were stimulated with ovalbumin and phytohemagglutinin and cellular proliferative response and concentrations of interleukin-13 and interferon-gamma, were measured. The risk of developing AD was greater in boys than girls (OR 1.97, 95% CI 1.26-3.09), infants delivered by cesarean section than vaginally (OR 1.93, 95% CI 1.14-3.26) and infants with than without parental history of AD (OR 2.34, 95% CI 1.29-4.24). The CBMC proliferative response to phytohemagglutinin stimulation was higher in infants with than without AD (P = 0.048), but no difference was observed in ovalbumin-stimulated cells (P = 0.771). Risk factors for the development of AD at 12 months include male gender, delivery by cesarean section and parental history of AD. Increased CBMC proliferative response to phytohemagglutinin stimulation may predict the development of AD at 12 months.
Subject(s)
Adult , Female , Humans , Infant , Male , Pregnancy , Cell Proliferation , Cesarean Section , Dermatitis, Atopic/diagnosis , Fetal Blood/cytology , Interferon-gamma/metabolism , Interleukin-13/metabolism , Leukocytes, Mononuclear/drug effects , Odds Ratio , Ovalbumin/toxicity , Phytohemagglutinins/toxicity , Predictive Value of Tests , Risk Factors , Sex FactorsABSTRACT
Since the risk of developing allergic disease increases in individuals exposed to allergens previously, even during the neonatal period, the immunologic status of a fetus may be important in the subsequent development of allergy. We evaluated the fetal factors to predict atopic dermatitis (AD) at 12 months in 412 infants of a COhort for Childhood Origin of Asthma and Allergic Diseases (COCOA) in the general Korean population. Cord blood mononuclear cells (CBMCs) were stimulated with ovalbumin and phytohemagglutinin and cellular proliferative response and concentrations of interleukin-13 and interferon-gamma, were measured. The risk of developing AD was greater in boys than girls (OR 1.97, 95% CI 1.26-3.09), infants delivered by cesarean section than vaginally (OR 1.93, 95% CI 1.14-3.26) and infants with than without parental history of AD (OR 2.34, 95% CI 1.29-4.24). The CBMC proliferative response to phytohemagglutinin stimulation was higher in infants with than without AD (P = 0.048), but no difference was observed in ovalbumin-stimulated cells (P = 0.771). Risk factors for the development of AD at 12 months include male gender, delivery by cesarean section and parental history of AD. Increased CBMC proliferative response to phytohemagglutinin stimulation may predict the development of AD at 12 months.
Subject(s)
Adult , Female , Humans , Infant , Male , Pregnancy , Cell Proliferation , Cesarean Section , Dermatitis, Atopic/diagnosis , Fetal Blood/cytology , Interferon-gamma/metabolism , Interleukin-13/metabolism , Leukocytes, Mononuclear/drug effects , Odds Ratio , Ovalbumin/toxicity , Phytohemagglutinins/toxicity , Predictive Value of Tests , Risk Factors , Sex FactorsABSTRACT
In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.
Subject(s)
Animals , Female , Mice , Antibodies, Helminth/blood , Chemokine CCL11/biosynthesis , Cytokines/biosynthesis , Gene Expression Profiling , Immunoglobulin E/blood , Interleukin-13/metabolism , Interleukin-4/metabolism , Interleukin-5/metabolism , Interleukins/biosynthesis , Mice, Inbred C57BL , Mice, Knockout , Receptor, PAR-2/metabolism , Th2 Cells/immunology , Trichinella spiralis/immunology , Trichinellosis/immunologyABSTRACT
PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated in many aspects of the airway pathology in asthma. TNF-alpha blocking strategies are now being tried in asthma patients. This study investigated whether TNF-alpha blocking therapy inhibits airway inflammation and airway hyperresponsiveness (AHR) in a mouse model of asthma. We also evaluated the effect of TNF-alpha blocking therapy on cytokine production and adhesion molecule expression. MATERIALS AND METHODS: Ovalbumin (OVA) sensitized BALB/c female mice were exposed to intranasal OVA administration on days 31, 33, 35, and 37. Mice were treated intraperitoneally with soluble TNF-alpha receptor (sTNFR) during the OVA challenge. RESULTS: There were statistically significant decreases in the numbers of total cell and eosinophil in bronchoalveolar lavage fluid (BALF) in the sTNFR treated group compared with the OVA group. However, sTNFR-treatment did not significantly decrease AHR. Anti-inflammatory effect of sTNFR was accompanied with reduction of T helper 2 cytokine levels including interleukin (IL)-4, IL-5 and IL-13 in BALF and vascular cell adhesion molecule 1 expression in lung tissue. CONCLUSION: These results suggest that sTNFR treatment can suppress the airway inflammation via regulation of Th2 cytokine production and adhesion molecule expression in bronchial asthma.