| 1. |
- Andersen, Grethe Neumann, et al.
(författare)
-
Bronchoalveolar matrix metalloproteinase 9 relates to restrictive lung function impairment in systemic sclerosis.
- 2007
-
Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 101:10, s. 2199-2206
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic sclerosis (SSc) is frequently associated with interstitial lung disease (ILD) often leading to lung fibrosis. In this study we investigated whether matrix metalloproteinase 9 (MMP-9) and its natural inhibitor; the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), would be associated with remodelling in ILD in SSc. Levels of total MMP-9, pro-MMP-9 and TIMP-1 were measured in bronchoalveolar lavage (BAL) fluid from nine SSc patients with ILD, seven SSc patients without ILD and 16 age- and sex-matched healthy controls. Total MMP-9 and pro-MMP-9 levels were significantly elevated in SSc patients with ILD, compared to levels in SSc patients without ILD and healthy controls. In SSc patients with ILD calculated active MMP-9 levels were significantly higher than in SSc patients without ILD and tended to be higher than in healthy controls. TIMP-1 levels were elevated in both patient groups compared to healthy controls. Total-, pro- and active MMP-9 levels as well as pro-MMP-TIMP-1 and active MMP-9/TIMP-1 ratios were inversely associated with total lung capacity. The present study suggests that MMP-9 plays a pathophysiological role in the remodelling in ILD and lung fibrosis associated with SSc, and may represent a new therapeutic target in this condition.
|
|
| 2. |
- Blomberg, Anders, et al.
(författare)
-
Patofysiologi vid KOL
- 2009
-
Ingår i: Lungmedicin. - Lund, Sweden : Studentlitteratur. - 9789144008479 ; , s. 371-385
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Löfdahl, Magnus J, et al.
(författare)
-
Increased intraepithelial T-cells in stable COPD
- 2008
-
Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 102:12, s. 1812-1818
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The airway epithelium is the first line of defence in the response to inhaled particles and irritants. Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterised by an irreversible loss of lung function, with cigarette smoking as a major risk factor. Here, we address intraepithelial T-cells in COPD, as these cells are a distinct T-cell subtype thought to have important regulatory functions. We hypothesised that intraepithelial T-cells play a role in the response to lung irritants and that the T-cell populations would be altered and associated with signs of inflammation in COPD. METHODS: Bronchoscopy with endobronchial mucosal biopsy sampling was performed in 22 patients (mean age; 57) with stable COPD (median FEV(1)% predicted: 51). Age- and smoking- matched smokers (S) with normal lung function (n=14) and age-matched non-smokers (NS) (n=15) served as controls. Airway inflammation was recorded visually using bronchitis index (BI). Biopsy specimens were processed into glycol methacrylate resin and inflammatory cells were stained immunohistochemically. RESULTS: The number of intraepithelial CD4+ T-cells were significantly higher in COPD patients compared to smokers as well as trend towards significance in non-smokers (p=0.005 and p=0.036, respectively), whereas intraepithelial CD8+ T-cells number were increased in patients with COPD compared to non-smokers (p=0.017). Both patients with COPD and smokers had a higher BI than non-smokers (p<0.001 for both). CONCLUSIONS: The present data suggest a role for intraepithelial CD4+ and CD8+ T-cells in stable COPD and indicate that T-cells are of importance in the long-term inflammatory response in COPD or, alternatively, play a regulatory role.
|
|
| 6. |
- Pourazar, Jamshid, 1953-
(författare)
-
Activation of epithelial signal transduction pathways, cytokine production and airway inflammation following diesel exhaust exposure
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
|
|
| 7. |
|
|
| 8. |
- Roos-Engstrand, Ester, 1962-, et al.
(författare)
-
Influence of smoking cessation on airway T lymphocyte subsets in COPD
- 2009
-
Ingår i: COPD. - : Informa UK Limited. - 1541-2563. ; 6:2, s. 112-120
-
Tidskriftsartikel (refereegranskat)abstract
- The mechanisms behind airway inflammation in chronic obstructive pulmonary disease (COPD) are still not well understood. Here we investigated lymphocyte subtypes in bronchoalveolar lavage fluid, likely to be involved in the pathogenesis of COPD, as well as exploring the effect of smoking cessation. Differential cell counts and T cell subsets were determined in BAL fluid from nineteen individuals with stable COPD (seven smokers, twelve ex-smokers) compared to twelve age-matched never-smokers and thirteen smoking-matched smokers with normal lung function. COPD-patients had higher percentages of airway CD8(+) T cells compared to never-smokers. An increased population of CD4(+) T cells expressed high levels of CD25 in smokers and COPD patients compared to never-smokers, suggesting the presence of regulatory T cells. As the T cell populations in smokers with normal lung function and COPD-patients were similar, the impact of current smoking in COPD was addressed in a subgroup analysis. Activation of CD8(+) T cells was found regardless of smoking habits. In contrast, the enhanced expression of gamma/delta T cells, was mainly associated with current smoking, whilst the increase in T regulatory cells appeared related to both smoking and COPD. Regardless of smoking habits, CD8(+) T cell activation was found in COPD, supporting the contention that this T cell subset may play a role in the pathogenesis of COPD. As CD8(+) T cells coexist with immunoregulatory CD4(+) T cells in airways of COPD patients, it is likely that both cytotoxic T-cell responses and immunosuppressive mechanisms may be of importance in COPD pathogenesis.
|
|
| 9. |
- Sehlstedt, Maria, 1979-, et al.
(författare)
-
Suppressed signal transduction in the bronchial epithelium of patients with systemic sclerosis
- 2009
-
Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 103:2, s. 301-308
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disorder, which frequently affects the lungs, with manifestations of interstitial lung disease (ILD) with lung fibrosis and of pulmonary hypertension. The pathogenesis remains largely unrecognised. OBJECTIVE: The aim of this study was to elucidate the inflammation in the bronchial mucosa in patients with SSc. SUBJECTS AND METHODS: Twenty-three subjects diagnosed with SSc participated. Twelve of the SSc patients showed signs of ILD, four were smokers and seven were treated with oral corticosteroids. Seventeen non-smoking, age- and sex-matched healthy subjects served as controls. Bronchoscopy was performed to sample endobronchial mucosal biopsies, which were immunohistochemically stained using a panel of antibodies against inflammatory markers. RESULTS: The number of neutrophils was significantly elevated in the submucosa of SSc patients, regardless of ILD, or whether the subject was smoking or using oral corticosteroids. No up-regulation of neutrophil chemoattractants or cytokines was seen in the bronchial epithelium. The signal transduction pathways and adhesion molecule expression tended to be suppressed or unchanged in SSc patients compared with controls. CONCLUSION: It is concluded that SSc is associated with a chronic neutrophilic inflammation in the bronchial mucosal, with signs of suppressed signal transduction, regardless of the presence of interstitial lung disease.
|
|
| 10. |
- Ahmadpour, Doryaneh, 1973, et al.
(författare)
-
Robustness analysis of HOG pathway genes in Saccharomyces cerevisiae
- 2006
-
Ingår i: YSBN Meeting Nov. 14-16, 2006- Vienna- Austria.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Robustness analysis of HOG pathway genes in Saccharomyces cerevisiae Doryaneh Ahmadpour1, Lars-Göran Ottosson1, Markus Krantz2, Jonas Warringer1, Anders Blomberg1 and Stefan Hohmann1* 1Department of Cell and Molecular Biology/Microbiology, Göteborg University, S-405 30 Göteborg, Sweden 2 The Systems Biology Institute (SBI), Shibuya, Tokyo, Japan E-mail: doryaneh.ahmadpour@gmm.gu.se Robustness is a fundamental property of biological systems and crucial for their effective function under internal or external perturbations. For instance, it has been proposed that internal parameters such as gene expression have been optimized during evolution such that a given system has the observed robustness. The permissible ranges of internal parameters in the cells are not comprehensively understood since there has not been a technique to measure such parameters. “Genetic tug-of-war” (gTOW) [1] is a genetic screening method that allows the investigation of the upper limit copy number of genes, and thereby the upper permissible range of gene expression level. This method is based on a 2-micron plasmid vector containing the leu2d allele with a very weak complementation activity and the gene of interest inserted as target gene. When the leu2ura3 deletion yeast cells transformed with pTOW plasmid are cultured under leucine-limiting conditions, there will be a bias toward increasing the plasmid copy number to compensate for the lack of leucine. On the other hand there will be an opposing bias toward decreasing the plasmid copy number if the target gene inhibits growth or has a toxic effect when a certain copy number is exceeded (it reaches to its upper limit). Eventually as a result of the “tug-of-war” between these two selection biases cells with optimized plasmid copy number will be concentrated. In this study we have applied the gTOW method on 29 HOG pathway related genes in Saccharomyces cerevisiae. The high osmolarity glycerol (HOG) MAPK pathway is essential for yeast survival in high osmolarity condition and consists of two branches that activate a MAPK (Hog1) via a MAPKK (Pbs2) to orchestrate part of the transcriptional response. The HOG pathway is the best understood osmoresponsive system in eukaryotes and the quantitative data provided by the gTOW method collating with the existing computational models could be used to analyze the robustness and fragility of the pathway. 1. Hisao Moriya, Yuki Shimizu-Yoshida and Hiroaki Kitano, 2006, PLoS Genetics, 2:7
|
|
