Holdings: Pharmacological modulation of the Th1/Th2 balance

Pharmacological modulation of the Th1/Th2 balance: a new concept for anti-asthmatic therapy

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Bibliographic Details
Main Author:	Zhang, Meixia 1964- (Author)
Format:	Thesis Book
Language:	English German
Published:	2003
Subjects:	Helferzelle Therapie Allergisches Asthma Hochschulschrift
Online Access:	Inhaltsverzeichnis
Item Description:	Erlangen-Nürnberg, Univ., Diss., 2003. - Enth. dt. Zs.fassung
Physical Description:	III, 100 S. Ill., graph. Darst.

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MARC


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adam_text	PHARMACOLOGICAL MODULATION OF THE TH1/TH2 BALANCE: A NEW CONCEPT FOR ANTI-ASTHMATIC THERAPY DEN NATURWISSENSCHAFTLICHEN FAKULTATEN DER FRIEDRICH-ALEXANDER UNIVERSITAT ERLANGEN-NIIRNBERG ZUR ERLANGUNG DES DOKTORGRADES VORGELEGT VON MEIXIA ZHANG AUS SHANDONG, P.R. CHINA CONTENTS 1 INTRODUCTION 1 1.1 PATHOPHYSIOLOGY OF ASTHMA 1 1.2 THL TH2 PARADIGM 2 1.3 T CELL ACTIVATION 3 1.4 ANTI-INFLAMMATORY THERAPY OF ASTHMA 6 1.5 MECHANISM OF APOPTOSIS 7 1.6 AIM OF THE STUDY 9 2 MATERIALS AND METHODS 11 2.1 MATERIALS 11 2.1.1 REAGENTS 11 2.1.2 PRIMERS AND PROBES 14 2.2 METHODS 14 2.2.1 PREPARATION OF PBMC 14 2.2.2 PREPARATION OF CD4+T CELL 14 2.2.3 PREPARATION OF MONOCYTES 15 2.2.4 CELL PROLIFERATION .7. 15 2.2.5 CELL TREATMENT AND CULTURE 15 2.2.6 CULTURE OF CELL LINES 15 2.2.7 RT-PCR 16 2.2.8 ELISA 16 2.2.9 MEASUREMENT OF HUMAN CD4+T CELL ANERGY 16 2.2.10 CHANGES OF PHOSPHATIDYLSERINE EXTERNALIZATION AND CELL MEMBRANE IMPAIRMENT * ANNEXIN-V AND PI ASSAY 17 2.2.11 CHANGES OF MITOCHONDRIAL MEMBRANE POTENTIAL * JC-1 ASSAY 17 2.2.12 CASPACE FITC-VAD-FMK IN SITU MARKER LABELING 18 CONTENTS 2.2.13 CASPATAG CASPASE-6 ACTIVITY ASSAY 18 2.2.14 WESTERN BLOTTING ANALYSIS 19 3 RESULTS 21 3.1 HUMAN IL-2, IL-4, IL-5 AND IFN-Y REGULATION BY DIFFERENT IMMUNOMODULATING DRUGS 21 3.1.1 TIME COURSE OF IL-2, IL-4, IL-5 AND IFN-Y INDUCTION IN HUMAN PBMC 21 3.1.2 EFFECTS OF INHIBITORS OF THE CALCIUM-*NF-AT PATHWAY 21 3.1.3 EFFECTS OF NF-KB INHIBITORS 26 3.1.4 EFFECTS OF MAPK INHIBITORS 29 3.1.5 IC50 VALUES OF DIFFERENT DRUGS FOR IL-2, IL-4,11-5 AND IFN-Y MRNA IN HUMAN PBMC 34 3.2 THE EFFECTS OF DIFFERENT IMMUNOMODULATING DRUGS ON HUMAN IL-13 34 3.2.1 INDUCTION OF IL-13 IN HUMAN PBMCS 35 3.2.2 TIME COURSE OF IL-13 INDUCTION 36 3.2.3 EFFECTS OF INHIBITORS OF THE CALCIUM-»NF-AT PATHWAY 37 3.2.4 EFFECTS OF NF-KB INHIBITORS 40 3.2.5 EFFECTS OF MAPK INHIBITORS 43 3.2.6 COMPARISON OF IC 50 OF PBMC WITH CD4+ T CELLS 46 3.3 THE EFFECT OF D-43787 ON HUMAN T CELL AND PROINFLAMMATORY CYTOKINES .47 3.3.1 DOSE RESPONSE EFFECT ON CELL PROLIFERATION 47 3.3.2 D-43787 DOES NOT INDUCE ANERGY IN HUMAN CD4+ T CELLS 49 3.3.3 D-43787 INHIBITS TH2 CYTOKINES 50 3.3.4 DOSE RESPONSE EFFECT ON THL/TH2 CYTOKINES 54 3.3.5 DOSE RESPONSE EFFECT ON PROINFLAMMATORY CYTOKINES 56 3.4 APOPTOTIC EFFECT OF D-43787 ON HUMAN CD4+ T CELLS 58 CONTENTS III 3.4.1 D-43787 INDUCES APOPTOSIS IN HUMAN CD4+ T CELLS 58 3.4.2 INDUCTION OF APOPTOSIS DEPENDS ON A SPECIFIC COMPOUND STRUCTURE AND A NEW BINDING SITE AT CYCLOPHILIN 60 3.4.3 D-43787 INDUCES DEPOLARIZATION OF MITOCHONDRIA IN CD4+ T CELLS.. 63 3.4.4 D-43787 ACTIVATES CASPASE-LIKE PROTEASES 64 3.4.5 CASPASE-6 MEDIATES INDUCTION OF APOPTOSIS BY D-43787 65 3.4.6 CLEAVAGE OF THE CASPASE-6 SUBSTRATE LAMIN A/C 68 4 DISCUSSION 71 4.1 THE EFFECTS OF DIFFERENT IMMUNOSUPPRESSIVE DRUGS ON HUMAN IL-2, IL-4, IL-5 AND IFN-Y REGULATION 72 4.2 THE EFFECTS OF DIFFERENT IMMUNOSUPPRESSIVE DRUGS ON HUMAN IL-13 REGULATION 75 4.3 THE EFFECT OF D-43787 ON HUMAN T CELL CYTOKINES AND PROINFLAMMATORY CYTOKINES 77 4.4 APOPTOTIC EFFECTS OF D-43787 ON HUMAN CD4+ T CELLS 79 5 SUMMARY 83 6 ZUSAMMENFASSUNG 85 7 REFERENCE 89 8 ACKNOWLEDGEMENT 101 9 CURRICULUM VITAE 102
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author	Zhang, Meixia 1964-
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spelling	Zhang, Meixia 1964- Verfasser (DE-588)128458690 aut Pharmacological modulation of the Th1/Th2 balance a new concept for anti-asthmatic therapy von Meixia Zhang 2003 III, 100 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Erlangen-Nürnberg, Univ., Diss., 2003. - Enth. dt. Zs.fassung Erlangen-Nürnberg, Univ., Diss., 2003 Helferzelle (DE-588)4258130-8 gnd rswk-swf Therapie (DE-588)4059798-2 gnd rswk-swf Allergisches Asthma (DE-588)4275602-9 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Allergisches Asthma (DE-588)4275602-9 s Therapie (DE-588)4059798-2 s Helferzelle (DE-588)4258130-8 s DE-604 GBV Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=010600398&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis
spellingShingle	Zhang, Meixia 1964- Pharmacological modulation of the Th1/Th2 balance a new concept for anti-asthmatic therapy Helferzelle (DE-588)4258130-8 gnd Therapie (DE-588)4059798-2 gnd Allergisches Asthma (DE-588)4275602-9 gnd
subject_GND	(DE-588)4258130-8 (DE-588)4059798-2 (DE-588)4275602-9 (DE-588)4113937-9
title	Pharmacological modulation of the Th1/Th2 balance a new concept for anti-asthmatic therapy
title_auth	Pharmacological modulation of the Th1/Th2 balance a new concept for anti-asthmatic therapy
title_exact_search	Pharmacological modulation of the Th1/Th2 balance a new concept for anti-asthmatic therapy
title_full	Pharmacological modulation of the Th1/Th2 balance a new concept for anti-asthmatic therapy von Meixia Zhang
title_fullStr	Pharmacological modulation of the Th1/Th2 balance a new concept for anti-asthmatic therapy von Meixia Zhang
title_full_unstemmed	Pharmacological modulation of the Th1/Th2 balance a new concept for anti-asthmatic therapy von Meixia Zhang
title_short	Pharmacological modulation of the Th1/Th2 balance
title_sort	pharmacological modulation of the th1 th2 balance a new concept for anti asthmatic therapy
title_sub	a new concept for anti-asthmatic therapy
topic	Helferzelle (DE-588)4258130-8 gnd Therapie (DE-588)4059798-2 gnd Allergisches Asthma (DE-588)4275602-9 gnd
topic_facet	Helferzelle Therapie Allergisches Asthma Hochschulschrift
url	http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=010600398&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
work_keys_str_mv	AT zhangmeixia pharmacologicalmodulationoftheth1th2balanceanewconceptforantiasthmatictherapy

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