Allergic Disorders and Pregnancy: from Clinic to Mechanism
博士 === 國立陽明大學 === 臨床醫學研究所 === 107 === Allergic disorders have progressively become a significant health problem worldwide. Maternal history was shown to be an important risk factor. However, little is known about the role of allergic sensitization in pregnancy and its impact on developing allergic d...
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博士 === 國立陽明大學 === 臨床醫學研究所 === 107 === Allergic disorders have progressively become a significant health problem worldwide. Maternal history was shown to be an important risk factor. However, little is known about the role of allergic sensitization in pregnancy and its impact on developing allergic disorders in the offspring. In the present study, we plan to explore pregnancy and allergic disorders in two parts: clinical presentation (determination of allergic sensitization in pregnancy) and immuno-pathological mechanism (pathways contribute to Fusarium-induced mediators release from human respiratory epithelial cells).
Determination of allergic sensitization in pregnancy
There is an increase in prevalence and financial burden of childhood atopic disorders in recent years. Understanding allergic conditions of pregnant women is important for developing strategies for prevention and management of allergy-related diseases. However, little is currently known about the atopic conditions in pregnant women. The sera from 46 pregnant women were analyzed for allergen-specific IgE antibodies using the Optigen assay and SDS-PAGE immunoblot analysis. Results from the Optigen assay showed that 20 (43%) of the 46 serum samples analyzed demonstrated IgE reactivity against mite p (Dermatophagoides pteronyssinus) (95%), mite f (D. farinae) (95%), house dust (60%), cat (25%), shrimp (20%), crab (15%), cockroach (10%), dog (5%), latex (5%), willow black (5%) and timothy grass (5%). Nineteen of the 20 Optigen-positive sera demonstrated IgE reactivity against both the house dust mites D. pteronyssinus and D. farina, with 10 of them having a high IgE CLA Class value of 4. IgE reactivity to the house dust mite D. pteronyssinus was confirmed in SDS-PAGE-immunoblots, which correlated well with the intensity of IgE-binding to the 15-kDa D. pteronyssinus component and to the purified recombinant Der p 2 major house dust mite allergen. A high prevalence of IgE sensitization against house dust mites during pregnancy is noted, which is worthy of clinical attention. Children of IgE-sensitized mothers should be closely monitored for development of allergenic disorders.
Pathways contribute to Fusarium-induced mediators release from human respiratory epithelial cells
Fusarium species are causative agents of human respiratory disorders and are distributed widely in our environment. Little is known of their interaction with human respiratory epithelial cells, which may contribute to allergic airway responses. In this study, we report on the release of C–X–C motif chemokine ligand 8 (CXCL-8) from human bronchial epithelial BEAS-2B cells upon stimulation with Fusarium proliferatum extracts. F. proliferatum-induced cytokine release from BEAS-2B cells was determined by cytokine array and CXCL-8 enzyme-linked immunosorbent assay (ELISA) kits. Blocking antibodies and signaling pathway inhibitors were employed to delineate cell surface receptors and signaling pathways participating in CXCL-8 release. F. proliferatum extracts induced the release of CXCL-8 in a time-dependent manner. The dectin-1 receptor ligands, curdlan and laminarin, reduced CXCL-8 release. Cells pre-treated with anti-Dectin-1 antibodies (2 ug/mL) decreased CXCL-8 release by 24%. Furthermore, F. proliferatum-stimulated CXCL-8 release was reduced by 32%, 53%-81%, 40% and 26% after BEAS-2B cells were pretreated with activation inhibitors of spleen tyrosine kinase (Syk)-piceatannol-, mitogen-activated protein kinases (MAPKs)-PD98059, U0126, SB202190, SP600125-, phosphatidylinositol-3-kinase (PI3K)-LY294002-, and nuclear factor k-light-chain-enhancer of activated B cells (NF-kB)-BAY117082-, respectively. These results suggest that Dectin-1-mediated activation of the Syk, MAPKs, PI3K and NF-kB signaling pathways contributes to F. proliferatum-stimulated CXCL-8 release from BEAS-2B cells and provides an important basis for developing novel therapeutic strategies in clinical allergy.
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author2 |
Peng-Hui Wang |
author_facet |
Peng-Hui Wang Chang-Ching Yeh 葉長青 |
author |
Chang-Ching Yeh 葉長青 |
spellingShingle |
Chang-Ching Yeh 葉長青 Allergic Disorders and Pregnancy: from Clinic to Mechanism |
author_sort |
Chang-Ching Yeh |
title |
Allergic Disorders and Pregnancy: from Clinic to Mechanism |
title_short |
Allergic Disorders and Pregnancy: from Clinic to Mechanism |
title_full |
Allergic Disorders and Pregnancy: from Clinic to Mechanism |
title_fullStr |
Allergic Disorders and Pregnancy: from Clinic to Mechanism |
title_full_unstemmed |
Allergic Disorders and Pregnancy: from Clinic to Mechanism |
title_sort |
allergic disorders and pregnancy: from clinic to mechanism |
publishDate |
2018 |
url |
http://ndltd.ncl.edu.tw/handle/645ud2 |
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AT changchingyeh allergicdisordersandpregnancyfromclinictomechanism AT yèzhǎngqīng allergicdisordersandpregnancyfromclinictomechanism AT changchingyeh guòmǐnxìngjíbìngyǔhuáiyùncónglínchuángdàojīzhuǎn AT yèzhǎngqīng guòmǐnxìngjíbìngyǔhuáiyùncónglínchuángdàojīzhuǎn |
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1719196835482959872 |
spelling |
ndltd-TW-107YM0055210092019-05-30T03:57:16Z http://ndltd.ncl.edu.tw/handle/645ud2 Allergic Disorders and Pregnancy: from Clinic to Mechanism 過敏性疾病與懷孕: 從臨床到機轉 Chang-Ching Yeh 葉長青 博士 國立陽明大學 臨床醫學研究所 107 Allergic disorders have progressively become a significant health problem worldwide. Maternal history was shown to be an important risk factor. However, little is known about the role of allergic sensitization in pregnancy and its impact on developing allergic disorders in the offspring. In the present study, we plan to explore pregnancy and allergic disorders in two parts: clinical presentation (determination of allergic sensitization in pregnancy) and immuno-pathological mechanism (pathways contribute to Fusarium-induced mediators release from human respiratory epithelial cells). Determination of allergic sensitization in pregnancy There is an increase in prevalence and financial burden of childhood atopic disorders in recent years. Understanding allergic conditions of pregnant women is important for developing strategies for prevention and management of allergy-related diseases. However, little is currently known about the atopic conditions in pregnant women. The sera from 46 pregnant women were analyzed for allergen-specific IgE antibodies using the Optigen assay and SDS-PAGE immunoblot analysis. Results from the Optigen assay showed that 20 (43%) of the 46 serum samples analyzed demonstrated IgE reactivity against mite p (Dermatophagoides pteronyssinus) (95%), mite f (D. farinae) (95%), house dust (60%), cat (25%), shrimp (20%), crab (15%), cockroach (10%), dog (5%), latex (5%), willow black (5%) and timothy grass (5%). Nineteen of the 20 Optigen-positive sera demonstrated IgE reactivity against both the house dust mites D. pteronyssinus and D. farina, with 10 of them having a high IgE CLA Class value of 4. IgE reactivity to the house dust mite D. pteronyssinus was confirmed in SDS-PAGE-immunoblots, which correlated well with the intensity of IgE-binding to the 15-kDa D. pteronyssinus component and to the purified recombinant Der p 2 major house dust mite allergen. A high prevalence of IgE sensitization against house dust mites during pregnancy is noted, which is worthy of clinical attention. Children of IgE-sensitized mothers should be closely monitored for development of allergenic disorders. Pathways contribute to Fusarium-induced mediators release from human respiratory epithelial cells Fusarium species are causative agents of human respiratory disorders and are distributed widely in our environment. Little is known of their interaction with human respiratory epithelial cells, which may contribute to allergic airway responses. In this study, we report on the release of C–X–C motif chemokine ligand 8 (CXCL-8) from human bronchial epithelial BEAS-2B cells upon stimulation with Fusarium proliferatum extracts. F. proliferatum-induced cytokine release from BEAS-2B cells was determined by cytokine array and CXCL-8 enzyme-linked immunosorbent assay (ELISA) kits. Blocking antibodies and signaling pathway inhibitors were employed to delineate cell surface receptors and signaling pathways participating in CXCL-8 release. F. proliferatum extracts induced the release of CXCL-8 in a time-dependent manner. The dectin-1 receptor ligands, curdlan and laminarin, reduced CXCL-8 release. Cells pre-treated with anti-Dectin-1 antibodies (2 ug/mL) decreased CXCL-8 release by 24%. Furthermore, F. proliferatum-stimulated CXCL-8 release was reduced by 32%, 53%-81%, 40% and 26% after BEAS-2B cells were pretreated with activation inhibitors of spleen tyrosine kinase (Syk)-piceatannol-, mitogen-activated protein kinases (MAPKs)-PD98059, U0126, SB202190, SP600125-, phosphatidylinositol-3-kinase (PI3K)-LY294002-, and nuclear factor k-light-chain-enhancer of activated B cells (NF-kB)-BAY117082-, respectively. These results suggest that Dectin-1-mediated activation of the Syk, MAPKs, PI3K and NF-kB signaling pathways contributes to F. proliferatum-stimulated CXCL-8 release from BEAS-2B cells and provides an important basis for developing novel therapeutic strategies in clinical allergy. Peng-Hui Wang 王鵬惠 2018 學位論文 ; thesis 47 en_US |