MMP-8, MMP-9 and Neutrophil Elastase in Peripheral Blood and Exhaled Breath Condensate in COPD.

Chronic obstructive pulmonary disease (COPD) is characterised by progressive and irreversible airflow limitation associated with chronic inflammation involving cytokines and metalloproteinases (MMPs). MMP-8, MMP-9 and neutrophil elastase (NE) are known to be implicated in COPD but the factors influencing activation and suppression remain unclear. This study aimed to compare MMP-8, MMP-9 and NE in the peripheral blood of COPD patients and controls and to likewise assess exhaled breath condensate (EBC) for these MMPs. Peripheral blood micro(mi)RNA139-5p levels, which may regulate MMPs in COPD, were also measured. Blood and EBC were collected from COPD patients (stable and during exacerbations) and healthy controls. Expression of mRNA for MMP-8, MMP-9, NE and miRNA-139-5p expression in peripheral blood mononuclear cells (PBMCs) was measured using qRT-PCR. MMP-8, MMP-9 and NE protein in plasma as well as MMP-8 and MMP-9 protein in EBC were analysed by enzyme-linked immunoassays. PBMCs from COPD patients showed greater expression of mRNA for MMP-8 (p = 0.0004), MMP-9 (p = 0.0023) and NE (p = 0.0019). PBMC expression of mRNA for NE was significantly higher in COPD exacerbations compared to stable cases (p < 0.05). Expression of mRNA for MMP-9 and NE correlated negatively with spirometry in patients (p < 0.05). Plasma from COPD patients showed greater levels of protein for MMP-8 (p = 0.003), MMP-9 (p = 0.046) and NE (p = 0.018). MMP-8 protein levels were lower in the EBC of COPD patients (p < 0.0001). In PBMCs, enhanced expression of mRNA for MMP-9 and NE is associated with COPD and may correlate with disease severity and exacerbations.

T-bet and interleukin-27: possible TH1 immunomodulators of sarcoidosis.

BACKGROUND: Sarcoidosis has often been termed an "immune paradox" as there is peripheral anergy to common recall antigens despite pronounced TH1-dominant inflammation at disease sites, such as the lung, with up-regulation of interferon γ, IL-27 and transcription factors. Peripheral blood may reflect the anergic state, while exhaled breath condensate (EBC) analysis may offer insights into the lung disease. METHODS: A cross-sectional study was conducted to investigate the expression of TH1 cytokines and transcription factors (IFNγ, IL-27 and T-bet) in the peripheral blood and/or EBC of sarcoidosis patients and healthy controls. Whole blood and EBC were collected from sarcoidosis patients and healthy controls. TH1 cytokine expression levels were then measured in peripheral blood mononuclear cells (PBMCs) and/or plasma and EBC using quantitative real-time PCR, ELISA and via Western blotting. RESULTS: Compared to healthy controls, PBMC IL-27 mRNA was higher in patients (p = 0.0019). There were no significant differences in plasma IL-27 protein between patients and controls (p = 0.20). T-bet mRNA and protein were lower (p = 0.010 and p = 0.0043, respectively) in patients compared to controls. There were no significant differences in PBMC IFNγ mRNA and protein expression (p = 0.68 and p = 0.74, respectively) nor in EBC IL-27 levels. CONCLUSIONS: Our data indicate that depressed T-bet mRNA and protein expression could contribute to the peripheral anergy in sarcoidosis and that IL-27 mRNA levels are elevated in the PBMC from those with sarcoidosis.

Asbestos and the lung in the 21st century: an update.

The asbestos-related disorders (ARDs) are currently of significant occupational and public health concern. Asbestos usage has been banned in most developed countries, but asbestos is still used in many developing countries and the number of cases of ARDs worldwide is rising. Many countries are now experiencing an epidemic of ARDs that is the legacy of occupational exposure in the 1960s-1980s because of the long latency period between asbestos exposure and manifestation of disease. It is likely that asbestos-related mortality and morbidity will continue to increase. Although the most feared complications of asbestos inhalation are the malignant conditions such as mesothelioma and lung cancer, asbestos inhalation more frequently results in benign conditions such as pleural plaques, diffuse pleural thickening, and asbestosis (pulmonary fibrosis due to asbestos exposure). Over recent years, there have been changes in the epidemiology of mesothelioma, in clinical management of ARDs and developments in new techniques for early detection of malignancy. This review provides an update on the respiratory manifestations of asbestos exposure and also considers advances in screening methods that may affect future management in the workplace.

[(TTTTA), polymorphism in the promoter of the CYP11A1 gene in the pathogenesis of polycystic ovary syndrome]. / Promotorový polymorfismus (TTTTA)n genu CYP11A1 v patogenezi syndromu polycystických ovarií.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrinopathy which is characterized by ovarian androgen excess. PCOS has a strong genetic component but the pathogenetic mechanisms responsible for hyperandrogenemia are still unknown. The CYP11A1 encodes the cholesterol side-chain cleavage enzyme that catalyzes the first and rate-limiting step of steroidogenesis. A promoter polymorphism (TTTTA)n CYP11A1 has been reported to be related to the risk of PCOS but the results were controversial. METHODS AND RESULTS: We determined this polymorphism in a cohort of 256 PCOS and 109 healthy control women. Using two models (dominant model for allele with 4 repeats and dominant model for long alleles, i.e. 7 and more repeats) we did not find either the difference in allele and genotype distribution between PCOS and controls or the influence of polymorphism on serum testosterone and androstendione levels. However, the PCOS carriers of long alleles had lower FSH, total- and LDL-cholesterol compared to the carriers of short alleles (p = 0.007; p = 0.02; p = 0.02, ANOVA). In controls, the non-carriers of allele with 4 repeats had significantly higher DHEA-S (p = 0.02, ANOVA) levels than the carriers of allele with 4 repeats. CONCLUSIONS: Despite of some associations found, it seems that the promoter variability of CYP11A1 does not play a key role in the pathogenesis of PCOS.