Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Enzymatic cleavage of HMGB1
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Karolinska Institutet, CMM, Rheumatology)
2017 (English)Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
Abstract [en]

Alarmins and damage associated molecular pattern (DAMP) are endogenous proteins with distinct and various intracellular roles that when released extracellularly act as startingsignals for inflammatory immune responses. The endogenous protein High mobility group box 1 (HMGB1) acts as a DAMP and has been shown to drive progression of multiple inflammatory and autoimmune diseases. During homeostasis HMGB1 is localized in the nucleus of almost any cell, where its main function is organization of the DNA and regulation of transcription. Upon cell death or immune cell activation HMGB1 can be translocated into the cytoplasm for subsequent release into the extracellular space. Extracellular HMGB1 can act as a DAMP by activating several receptors of the immune system. Recent studies focus on HMGB1 release and functional regulation due to prost-translational modifications (PTMs) on cysteine residues. However, little is known about enzymatic regulation of HMGB1. The aim of this thesis was to investigate the possibility of proteolytic processing of HMGB1 by enzymes, which play a crucial role in inflammatory diseases and their progression. We utilized an in vitro model that mimics natural conditions of the autoimmune disease arthritis. Enzymatic digestion of HMGB1 was performed in kinetics studies using the neutrophilic enzymes cathepsin G, neutrophil Elastase as well as matrix metalloproteinase-3, which is released from tissues at the site of inflammation. We defined that HMGB1 is a novel substrate of all of the tested enzymes. All enzymes induced different cleavage pattern. In conclusion, my findings open up the possibility for future studies involving the observed fragments of HMGB1 and their functional features. It also demonstrated that HMGB1 is affected by protease modifications in a disease relevant environment.

Place, publisher, year, edition, pages
2017.
Keywords [en]
HMGB1, enzymatic cleavage, neutrophil Elastase, cathepsin G, matrix metalloproteinase-3, arthritis
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-331333OAI: oai:DiVA.org:uu-331333DiVA, id: diva2:1148901
External cooperation
Karolinska Institutet
Educational program
Master Programme in Infection Biology
Supervisors
Examiners
Available from: 2017-11-17 Created: 2017-10-12 Last updated: 2017-11-20Bibliographically approved

Open Access in DiVA

fulltext(3374 kB)61 downloads
File information
File name FULLTEXT01.pdfFile size 3374 kBChecksum SHA-512
95c1bf5acdd6cb3abf273b3908d23ad138cddff0846c0fbe9604d9172d8ee6d5c30dfd07f9dadfb58e5107990338eda136e520323ac6ad4c42a3afd897c61b4c
Type fulltextMimetype application/pdf

By organisation
Department of Medical Biochemistry and Microbiology
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 61 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

urn-nbn

Altmetric score

urn-nbn
Total: 1148 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf