umu.sePublications
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
Diesel exhaust exposure enhances the expression of IL-13 in the bronchial epithelium of healthy subjects.
Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Pulmonary Medicine.
Show others and affiliations
2004 (English)In: Respiratory Medicine, ISSN 0954-6111, Vol. 98, no 9, 821-825 p.Article in journal (Refereed) Published
Abstract [en]

Epidemiological studies have demonstrated adverse health effects of environmental pollution. Diesel exhaust (DE) is an important contributor to ambient particulate matter pollution. DE exposure has been shown to induce a pronounced inflammatory response in the airways, with an enhanced epithelial expression of IL-8, and Gro-α in healthy subjects. The present investigation was aimed to further characterise the epithelial response to DE in vivo, with particular reference to possible TH2 response, in non-atopic healthy subjects. To determine this response, 15 healthy, non-atopic non-smoking subjects with normal lung function were exposed to DE (PM10 300 μg/m3) and filtered air during 1 h on two separate randomised occasions. Bronchoscopy sampling of bronchial mucosal biopsies was performed 6 h after exposure. Immunohistochemical staining were performed using mAb for IL-10, IL-13 and IL-18 expression. DE exposure induced a significant increase in the expression of IL-13 in the bronchial epithelium cells, 2.1 (1.35–4.88) Md (Q1–Q3) vs. air 0.94 (0.53–1.23); P=0.009. No significant changes were seen in IL-10 and IL-18 expression. This finding suggests an TH2-inflammatory response in the airways of non-atopic healthy individuals.

Place, publisher, year, edition, pages
2004. Vol. 98, no 9, 821-825 p.
Keyword [en]
Adult, Air Pollutants/*toxicity, Bronchi/*immunology, Environmental Exposure/adverse effects, Epithelium/immunology, Female, Humans, Immunohistochemistry/methods, Interleukin-13/*analysis, Male, Respiratory Mucosa/immunology, T-Lymphocytes; Helper-Inducer/immunology, Vehicle Emissions/*toxicity
Identifiers
URN: urn:nbn:se:umu:diva-13124DOI: 10.1016/j.rmed.2004.02.025PubMedID: 15338792OAI: oai:DiVA.org:umu-13124DiVA: diva2:152795
Available from: 2007-05-02 Created: 2007-05-02 Last updated: 2009-10-28Bibliographically approved
In thesis
1. Activation of epithelial signal transduction pathways, cytokine production and airway inflammation following diesel exhaust exposure
Open this publication in new window or tab >>Activation of epithelial signal transduction pathways, cytokine production and airway inflammation following diesel exhaust exposure
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Adverse health effects of ambient air pollution are well recognised and include increased morbidity and mortality in respiratory and cardiovascular diseases. Diesel engines are major contributors to ambient particulate matter pollution and diesel particles have been shown to have strong toxicological and oxidative properties.

Mechanistic aspects of diesel engine exhaust exposure have been investigated in bronchial mucosal biopsies sampled during bronchoscopy of human subjects exposed in a validated experimental exposure set-up. Two exposure series were performed. Two separate groups of 15 healthy subjects each were exposed to filtered air and diesel exhaust during 1 hour in random order. The first exposure series was performed with the engine at idling with a PM10 concentration of 300µg/m3 and the second was carried out during urban cycle (European Transient Cycle) running conditions with 270 µg particles/m3. Bronchoscopies with sampling of bronchial mucosal biopsies were performed 6 hours after exposure. Biopsies fixed in acetone were bedded in glycolmethacrylate (GMA) resin and were stained for immunohistochemistry. Readings were done with light microscopy as well as image analyser with digital stainings processing of.

Diesel exhaust enhanced the expression of the cytokines IL-8 and GRO-α in the bronchial epithelium suggesting that the epithelium plays a major role in mediating the neutrophil-dominated airway mucosal inflammation. The bronchial expression of Th1 and Th2 cytokines was evaluated, addressing the hypothesis that diesel exhaust would induce a Th2 airway response. Diesel exhaust enhanced the expression of Th2 related cytokine IL-13 whereas the expression of Th1 cytokines was unaffected.

The investigation of epithelial signal transduction pathways, by means of newly developed and validated cytoplasmic and nuclear stainings for key transcription factors and kinases, demonstrated that exposure to diesel exhaust increased the nuclear translocation of redox sensitive signal transduction components including phosphorylated (p)-p38-MAPK, p-JNK, p-c-jun (AP-1) and p65 (NFκB). These findings indicate novel mechanistic aspects to be involved in the airway response to particulate air pollution.

The expression of epidermal growth factor receptor (EGFR) as well as phosphorylated C-terminal Tyr 1173 increased significantly following DE exposure. The findings are consistent with the upregulation of p38 and JNK MAPkinases as well as increased NFκB expression. The MEK-ERK pathway was not affected and Src related phosphorylation was absent.

Diesel exposure at urban European transient cycle running conditions resulted in upregulation of the vascular adhesion molecule expression in the bronchial mucosa as signs of an early inflammatory response, while infiltration of inflammatory cells had not yet occurred. Differences in organic composition and particle concentration in the exhaust compared to idling situation may have influenced the outcome.

This thesis has added a mechanistic basis for the diesel exhaust induced airway inflammation in-vivo in humans. It is concluded that activation of epithelial signal transduction pathways, cytokine production and increased endothelial adhesion molecule expression play important roles in the airway inflammatory response to diesel exhaust.

Place, publisher, year, edition, pages
Umeå: Folkhälsa och klinisk medicin, 2006
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1033
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-795 (URN)91-7264-102-9 (ISBN)
Public defence
2006-06-02, Sal 9B, Tandläkarhögskolan, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2006-05-11 Created: 2006-05-11 Last updated: 2016-08-17Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=15338792&dopt=Citation

Authority records BETA

Pourazar, JamshidBlomberg, AndersSandström, Thomas

Search in DiVA

By author/editor
Pourazar, JamshidBlomberg, AndersSandström, Thomas
By organisation
Pulmonary Medicine
In the same journal
Respiratory Medicine

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 84 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