On the role of interleukin 36 in host defense against Mycobacterium tuberculosis:
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| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
Berlin
2017
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | 127 Seiten Illustrationen, Diagramme |
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MARC
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|---|---|---|---|
| 001 | BV044426105 | ||
| 003 | DE-604 | ||
| 005 | 20220628 | ||
| 007 | t | ||
| 008 | 170726s2017 a||| m||| 00||| eng d | ||
| 035 | |a (OCoLC)1013468798 | ||
| 035 | |a (DE-599)BVBBV044426105 | ||
| 040 | |a DE-604 |b ger |e rda | ||
| 041 | 0 | |a eng | |
| 049 | |a DE-11 | ||
| 084 | |a YE 1604 |0 (DE-625)153370:12910 |2 rvk | ||
| 100 | 1 | |a Ahsan, Fadhil |d 1985- |e Verfasser |0 (DE-588)1137384514 |4 aut | |
| 245 | 1 | 0 | |a On the role of interleukin 36 in host defense against Mycobacterium tuberculosis |c von Fadhil Ahsan |
| 264 | 1 | |a Berlin |c 2017 | |
| 300 | |a 127 Seiten |b Illustrationen, Diagramme | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Humboldt-Universität zu Berlin |d 2017 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 776 | 0 | 8 | |i Reproduziert als |a Ahsan, Fadhil |t On the role of interleukin 36 in host defense against Mycobacterium tuberculosis |d Ketsch bei Mannheim : Mikroform Dissertation, 2017 |h 2 Mikrofiches |w (DE-604)BV044868753 |
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| 999 | |a oai:aleph.bib-bvb.de:BVB01-029827593 | ||
Record in the Search Index
| _version_ | 1804177724725526528 |
|---|---|
| adam_text | LIST OF CONTENTS
ABSTRACT..........................................................................................................................
8
ZUSAMMENFASSUNG.......................................................................................................9
INTRODUCTION................................................................................................................
11
1. MYCOBACTERIUM TUBERCULOSIS (MTB)
...........................................................................11
1.1. GLOBAL PERSPECTIVE ON
TUBERCULOSIS........................................................................11
1.2. GENERAL FEATURES OF THE
PATHOGEN........................................................................13
1.3. CELL ENVELOPE STRUCTURE
..........................................................................................
14
2. HOST INNATE IM M UNITY TO M TB
.....................................................................................
16
2.1. MACROPHAGE AS ONE OF THE MAJOR INNATE
CELLS...................................................... 16
2.1.1. ALVEOLAR
MACROPHAGE....................................................................................
16
2.1.2. ACTIVATION OF MACROPHAGE AND ANTIBACTERIAL EFFECTORS
.................................
17
2.2. SENSING MTB: ROLE OF TLRS AND OTHER
RECEPTORS................................................... 18
2.3. ROLE OF EFFECTOR PROTEINS: ANTIMICROBIAL PEPTIDES AND CYTOKINES
..........................
21
2.3.1. ANTIMICROBIAL
PEPTIDES...................................................................................21
2.3.2. THE MAIN CYTOKINES: TNF, IFNY AND
IL-1.....................................................22
3. INTERLEUKIN 36 AS THE FAM ILY MEMBER OF IL -1
............................................................23
3.1. OVERVIEW OF IL-1 FAM
ILY..........................................................................................
23
3.1.1. EXPRESSION PATTERN AND PROTEOLYTIC PROCESSING
...........................................
26
3.1.2. SIGNALING CASCADE AND IMMUNE
EFFECTORS.....................................................27
3.2. STRUCTURE AND EXPRESSION OF IL-36
CYTOKINES.........................................................27
3.3. IL-36 RECEPTOR AND DOWNSTREAM
SIGNALING.............................................................
29
4. LIVER X RECEPTOR
(LXR)..............................................................................................
30
4.1. EXPRESSION AND ACTIVATION OF LXR
.........................................................................
30
4.2. REGULATION OF HOST
CHOLESTEROL...............................................................................31
4.3. ROLE OF LXR IN
TUBERCULOSIS...................................................................................32
AIM OF THE PRESENT
STUDY.......................................................................................
33
MATERIALS AND
METHODS..........................................................................................
34
1.
MATERIALS.......................................................................................................................
34
2. HUMAN PRIM ARY CELLS AND CELL LIN E S
.........................................................................
34
3. M ICE
.....................................................................
34
4. B
ACTERIA.........................................................................................................................35
5. V IRU S
..............................................................................................................................35
6.
METHODS........................................................................................................................35
6.1. CELL
CULTURES...........................................................................................................
35
6.1.1. HUMAN CELL CULTURE AND MACROPHAGE
DIFFERENTIATION...................................35
6.1.2. MURINE BONE MARROW ISOLATION AND MACROPHAGE
DIFFERENTIATION.................36
6.2. BACTERIAL CULTURE AND IN VITRO
INFECTION..................................................................37
6.3. ASSESSMENT OF GENE
EXPRESSION...........................................................................37
6.3.1. RNA
EXTRACTION...............................................................................................37
6.3.2. REVERSE TRANSCRIPTION AND REAL TIME QUANTITATIVE PCR
(QPCR)..................37
6.4. ENZYME-LINKED IMMUNOSORBENT ASSAY
(ELISA)...................................................38
6.5. WESTERN BLOT
ANALYSIS.............................................................................................38
6.6. GENERATION OF GENETICALLY MODIFIED THP-1
CELLS...................................................39
6.6.1. LENTIVIRUS
PRODUCTION.....................................................................................
39
6.6.2. LENTIVIRUS TRANSDUCTION AND CELL
SELECTION....................................................39
6.7. ISOLATION OF MYCOBACTERIAL GENOMIC DMA AND R N A
............................................
40
6.6. CELL
STIMULATIONS.....................................................................................................
41
6.9. ENDOTOXIN
ASSESSMENT..........................................................................................
41
6.10. CELL VIABILITY
ASSESSMENT.....................................................................................
42
6.10.1. CYTOTOXICITY
ASSAY.......................................................................................
42
6.10.2. MTS VIABILITY
ASSAY.....................................................................................
42
6.11. IN SILICO CLEAVAGE SITE
PREDICTION..........................................................................42
6.12. ASSESSMENT OF BACTERIAL
REPLICATION.....................................................................43
6.12.1. [3H]-URACIL UPTAKE
ASSAY............................................................................43
6.12.2. COLONY FORMING UNIT
ASSAY..........................................................................43
6.13. LUCIFERASE
ASSAY..................................................................................................44
6.14. IN SILICO PREDICTION OF TRANSCRIPTION FACTOR BINDING
SITES......................................44
6.15. ASSESSMENT OF
CHOLESTEROL..................................................................................
44
6.15.1. CHOLESTEROL/ CHOLESTERYL ESTER QUANTIFICATION
.............................................
44
6.15.2. FILIPIN III FREE CHOLESTEROL STAINING
..............................................................
44
6.15.3. CHOLESTEROL
EFFLUX........................................................................................
44
6.16. STATISTICAL
ANALYSIS................................................................................................45
RESULTS............................................................................................................................
46
1. REGULATION OF IL-36 EXPRESSION UPON MTB INFECTION
..............................................
46
1.1. IL-36Y EXPRESSION UPON MTB INFECTION
..................................................................
46
1.2. MYD88-TLR2/4-DEPENDENT IL-36Y PRODUCTION UPON MTB INFECTION
....................
46
1.3. MTB LIPOPROTEINS/LIPOGLYCANS AND HEAT SHOCK PROTEINS
INDUCE IL-36Y UP-REGULATION VIA TLR2 AND TLR 4
...............................................
50
1.4. CASPASE-1 AND INFLAMMASOME CONTRIBUTE TO AMPLIFICATION OF
IL-36Y.................52
1.5. IL-1 SS AND IL-18 ARE SUFFICIENT FOR CASPASE/INFLAMMASOME-DEPENDENT
INDUCTION OF
IL-36Y.................................................................................................53
1.6. IL-1R1 AND IL-18R1 ARE ESSENTIAL FOR LATE-STAGE
AMPLIFICATION OF IL-36Y
LEVELS.................................................................................57
2. 11,-36 SIGNALING MODULATES MACROPHAGE HOST DEFENSE AGAINST M TB
.................59
2.1. IL-36 SIGNALING INHIBITS MTB GROWTH
......................................................................
59
2.2. IL-36 MEDIATES ANTIMICROBIAL PEPTIDE PRODUCTION
................................................
61
2.3. IL-36 SIGNALING FACILITATES LXR ACTIVATION UPON MTB INFECTION
.............................
63
2.4. RECOMBINANT IL-36Y FACILITATES THE PRODUCTION OF
ENDOGENOUS LXR
LIGANDS.......................................................................................
66
2.5. IL-36-INDUCED HOST DEFENSE IN MACROPHAGE IS
LXR-DEPENDENT........................66
2.6. IL-36/LXR AXIS CONTRIBUTES TO CHOLESTEROL METABOLISM
........................................
73
2.7. SUPPRESSION OF INTRACELLULAR CHOLESTEROL SYNTHESIS REDUCES MTB
GROWTH
............
77
DISCUSSION.....................................................................................................................
80
1. MAIN FINDINGS O F THE PRESENT S TU D Y
......................................................................
80
2. REGULATION O F IL-36 EXPRESSION UPON INFECTION AND STIM ULATION
BY MICROBIAL LIG A N D
S................................................................................................81
3. THE ROLE OF INFLAMMASOME AND PROTEASES IN IL-36 EXP RE SSIO N
.......................
82
4. CROSSTALK BETWEEN IL-36 AND LXR S IG N A LIN G
.......................................................83
5. ROLE O F IL-36/LXR AXIS IN CHOLESTEROL METABOLISM AND HOST DEFENSE
.............
84
6. OUTLOOK AND FUTURE
DIRECTION..................................................................................86
REFERENCES...................................................................................................................
88
ACKNOWLEDGEMENTS................................................................................................107
COPYRIGHT
PERMISSION.............................................................................................108
SELBSTAENDIGKEITSERKLAERUNG.............................................................................109
ABBREVIATIONS............................................................................................................
110
APPENDICES...................................................................................................................114
1. M
ATERIALS......................................................................................................................114
1.1.
ANTIBODIES.............................................................................................................
114
1.2. BUFFERS AND
MEDIA.................................................................................................115
1.3.
REAGENTS..............................................................................................................
115
1.4. COMMERCIAL
KITS....................................................................................................
118
1.5.
PRIMERS..................................................................................................................118
1.6. PLASTIC
WARES.............................................................................................
120
1.7. INSTRUMENTS............................. 121
1.8.
SOFTWARE.................................................................................................................122
1.9.
SUPPLIERS................................................................................................................122
2. PUBLICATIONS AND SCIENTIFIC
MEETINGS....................................................................125
2.1.
PUBLICATIONS...........................................................................................................125
2.2. ORAL
PRESENTATIONS................................................................................................
125
2.3. POSTER
PRESENTATIONS.............................................................................................
125
3. CURRICULUM
VITAE.......................................................................................................
126
|
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| spelling | Ahsan, Fadhil 1985- Verfasser (DE-588)1137384514 aut On the role of interleukin 36 in host defense against Mycobacterium tuberculosis von Fadhil Ahsan Berlin 2017 127 Seiten Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Dissertation Humboldt-Universität zu Berlin 2017 (DE-588)4113937-9 Hochschulschrift gnd-content Reproduziert als Ahsan, Fadhil On the role of interleukin 36 in host defense against Mycobacterium tuberculosis Ketsch bei Mannheim : Mikroform Dissertation, 2017 2 Mikrofiches (DE-604)BV044868753 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029827593&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Ahsan, Fadhil 1985- On the role of interleukin 36 in host defense against Mycobacterium tuberculosis |
| subject_GND | (DE-588)4113937-9 |
| title | On the role of interleukin 36 in host defense against Mycobacterium tuberculosis |
| title_auth | On the role of interleukin 36 in host defense against Mycobacterium tuberculosis |
| title_exact_search | On the role of interleukin 36 in host defense against Mycobacterium tuberculosis |
| title_full | On the role of interleukin 36 in host defense against Mycobacterium tuberculosis von Fadhil Ahsan |
| title_fullStr | On the role of interleukin 36 in host defense against Mycobacterium tuberculosis von Fadhil Ahsan |
| title_full_unstemmed | On the role of interleukin 36 in host defense against Mycobacterium tuberculosis von Fadhil Ahsan |
| title_short | On the role of interleukin 36 in host defense against Mycobacterium tuberculosis |
| title_sort | on the role of interleukin 36 in host defense against mycobacterium tuberculosis |
| topic_facet | Hochschulschrift |
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