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Identification of mechanisms behind tissue destruction in chronic infection/inflammation with focus on the regulation of MMP-8 and IL-6 production

Odlén, Karin (2019) MOBM02 20182
Degree Projects in Molecular Biology
Popular Abstract
Identification of mechanisms behind tissue destruction in caries

Caries is a common problem in everyday life and the disease is characterized by destruction of the hard tissues of the teeth allowing for bacteria to enter the cavities formed and finally reach the pulp tissue. There are two types of bacteria: gram-positive and gram-negative bacteria where gram-positive bacteria are thought to be the predominant ones in the disease-process of caries. Odontoblasts form a single cell layer between the dentin and the pulp tissue and have been identified as a potential barrier protecting the vascular and innervated pulp. The physiological and pathophysiological importance of this cell type is not completely understood.

Odontoblasts are... (More)
Identification of mechanisms behind tissue destruction in caries

Caries is a common problem in everyday life and the disease is characterized by destruction of the hard tissues of the teeth allowing for bacteria to enter the cavities formed and finally reach the pulp tissue. There are two types of bacteria: gram-positive and gram-negative bacteria where gram-positive bacteria are thought to be the predominant ones in the disease-process of caries. Odontoblasts form a single cell layer between the dentin and the pulp tissue and have been identified as a potential barrier protecting the vascular and innervated pulp. The physiological and pathophysiological importance of this cell type is not completely understood.

Odontoblasts are large columnar cells located at the bottom/side of the pulp and they are thought to play an important role in tooth repair as they produce and restore dentin. Dentin is a calcified tissue that contains a lot of collagen located within the teeth, just under the enamel layer. Odontoblasts produce most of the collagen needed in dentin. The functional importance of odontoblasts in innate immunity is not that extensively investigated.

The aim of this project was to get a better understanding of odontoblast, specifically what triggers them to produce pro-inflammatory factors and specific modulators within the cells to activate immune responses. This was done by stimulating odontoblast-like MDPC-23 cells, with virulent components of gram-positive bacteria and gram-negative bacteria, respectively. Gene expression was observed for three different genes involved in immune function (MMP-8, IL-6, MCP-1). Protein expression was then observed for MMP-8 and IL-6. Lastly, one aim was to try to identify the mechanism behind increase of IL-6 expression observed in cells stimulated with LTA. Hereby, we investigated proteins of the NF-κB complex, an immune activating pathway.

When stimulated with a virulent component of gram-positive bacteria, IL-6 showed a significant increase in both gene and protein expression. On the other hand, it was not affected by stimulation with the gram-negative component. None of the other immune modulators (MMP-8 and MCP-1) were affected by either component of gram-positive or gram-negative bacteria. The same observations as above were made when looking at the protein level. No increase in protein expression was observed for any of the proteins of the NF-κB complex. This might indicate that the NF-κB pathway is not involved in the increase of IL-6 expression through stimulation by a gram-positive component although this can´t be confirmed as no positive control was used.

Identifying factors and mechanisms that affect immune function in teeth can help understanding the mechanisms behind caries and inflammation of the pulp tissue better. This can help to prevent formation of caries and secondary inflammation of the pulp by targeting specific factors produced by odontoblasts to decrease bacterial activity in caries.

Master’s Degree Project in Molecular Biology 30 credits Fall 2018
Department of Biology, Lund University
Advisor: Bengt-Olof Nilsson
Vascular Physiology group, Department of Experimental Medical Science, BMC (Less)
Please use this url to cite or link to this publication:
author
Odlén, Karin
supervisor
organization
course
MOBM02 20182
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8969008
date added to LUP
2019-01-31 11:55:53
date last changed
2019-01-31 11:55:53
@misc{8969008,
  author       = {{Odlén, Karin}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Identification of mechanisms behind tissue destruction in chronic infection/inflammation with focus on the regulation of MMP-8 and IL-6 production}},
  year         = {{2019}},
}