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Modulation of Osteopontin Production and Chemokine-derived Fragments as Host Defense Peptides

Uppalapati, Kanthi Rekha (2017) MOBN01 20161
Degree Projects in Molecular Biology
Popular Abstract
Our bodies are defended by inborn protective strategies aimed against microorganisms, the so-called innate immune system. In this system, small peptide molecules characterized by positive charge serve as antibiotics. During allergic reactions, as exemplified hay fever and asthma, molecules named eotaxins are released. These attract a group of white blood cells named eosinophils to sites of inflammation, for example in the lung. Chronic obstructive pulmonary disease (COPD) is a common respiratory disease associated with a limitation of the airflow leading to difficulties in breathing. In COPD, deteriorations called exacerbations are frequently seen. In approximately 25% of these, there are signs of allergic inflammation, including presence... (More)
Our bodies are defended by inborn protective strategies aimed against microorganisms, the so-called innate immune system. In this system, small peptide molecules characterized by positive charge serve as antibiotics. During allergic reactions, as exemplified hay fever and asthma, molecules named eotaxins are released. These attract a group of white blood cells named eosinophils to sites of inflammation, for example in the lung. Chronic obstructive pulmonary disease (COPD) is a common respiratory disease associated with a limitation of the airflow leading to difficulties in breathing. In COPD, deteriorations called exacerbations are frequently seen. In approximately 25% of these, there are signs of allergic inflammation, including presence of eosinophils. In such exacerbations, several bacterial species may be seen, most likely contributing to the severity of exacerbations. In this study, we investigated whether eotaxins could serve as antibiotics, thus being of potential use as therapeutic agents. This may be important since many bacteria show increasing resistance against conventional antibiotics. Both the intact eotaxins and fragments killed different kinds of bacteria. We also found that the eotaxins and fragments neutralized the increased inflammation caused by a bacterial toxin named lipopolysaccharide (LPS). Taken together, in this first part of the project, it was shown that eotaxins may have a potential as antibacterial and anti-inflammatory agents, for example when treating COPD.

Cigarette smoking is the most common cause of COPD, causing longstanding inflammation and lung tissue damage. In the second part of the project, we speculated that osteopontin (OPN) a protein produced by all immune cells and tissues in the body may play important roles, protecting against inflammation and the resulting tissue-injury in the airways during COPD. We investigated how cigarette smoke extract affects OPN-production in isolated mucosal cells from the airways. To resemble airways, the cells were grown in contact with air and thereafter stimulated with medium that had been incubated with cigarette smoke. The quantity of OPN released by the mucosal cells increased both with time and the dose of cigarette smoke extract. Toxins from bacteria and small signaling molecules of the immune system (so-called cytokines) were also investigated for effects on OPN-production by mucosal cells. In particular nicotine of tobacco and a cytokine stimulating allergic inflammation (i.e. IL-4) increased OPN-production. A pharmacological agent inhibiting allergic inflammation (i.e. montelukast) decreased OPN-production caused by cigarette smoke extract, indicating involvement of lipid-derived inflammatory agents in regulation of the expression. The findings demonstrate novel avenues to modulate OPN-production in the airways, for example to dampen inflammation and the resulting tissue-damage in COPD.


Master’s Degree project in Molecular Biology, 45 credits
Department of Biology, Lund University.

Supervisor: Arne Egesten
Department of Respiratory Medicine, BMC (Less)
Please use this url to cite or link to this publication:
author
Uppalapati, Kanthi Rekha
supervisor
organization
course
MOBN01 20161
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8925115
date added to LUP
2017-09-08 15:27:21
date last changed
2017-09-08 15:27:21
@misc{8925115,
  author       = {Uppalapati, Kanthi Rekha},
  language     = {eng},
  note         = {Student Paper},
  title        = {Modulation of Osteopontin Production and Chemokine-derived Fragments as Host Defense Peptides},
  year         = {2017},
}