The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune-driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence-related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging.

• Klíčová slova
• cell metabolism, immune senescence, immunometabolism, inflammaging, senolytic drugs, senomorphic drugs,
• MeSH
• chronická nemoc MeSH
• chronická obstrukční plicní nemoc metabolismus   farmakoterapie   imunologie   MeSH
• lidé MeSH
• metabolické sítě a dráhy * MeSH
• plicní nemoci etiologie   farmakoterapie   metabolismus   imunologie   MeSH
• stárnutí buněk * účinky léků   MeSH
• stárnutí imunologie   metabolismus   MeSH
• zánět metabolismus   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

UNLABELLED: This study was designated to estimate protective role of ETA and ETB receptor antagonist against endothelin 1 (ET-1)-induced oxidative stress in lungs and determine whether these effects are mediated by nitric oxide (NO) synthase. Experiments were performed on Wistar rats divided into the following groups: I - saline (0.9 % NaCl); II - ET-1 (3 microg/kg b.w.), III - BQ123 (1 mg/kg b.w.) + ET-1 (3 microg/kg b.w.), IV - BQ788 (3 mg/kg b.w.) + ET-1 (3 microg/kg b.w.), V - N-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg b.w.) + ET-1 (3 microg/kg b.w.). ETA and ETB receptor antagonists or L-NAME were administered 30 min before ET-1 injection. The levels of the following substances were measured in the lungs homogenates: thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), reduced glutathione (GSH) and tumor necrosis factor-alpha (TNF-alpha). The results showed that ET-1 significantly increased TBARS, H(2)O(2) (respectively: p<0.001, p<0.02) and TNF-alpha levels (p<0.02) and decreased the GSH level (p<0.01) vs. CONTROL GROUP: On the other hand, prior administration of ETA receptor blocker (BQ123) significantly attenuated TBARS (p<0.01), H(2)O(2) (p<0.02), TNF-alpha (p<0.02) and increased GSH (p<0.02) levels vs. ET-1. However, prior administration of ETB receptor blocker BQ788 did not cause significant changes in the: TBARS, H(2)O(2) and TNF-alpha (p>0.05) levels, but significantly increased the GSH level and GSH/GSSG ratio (p<0.05). Administration of L-NAME significantly attenuated TBARS (p<0.001), H(2)O(2) (p<0.05), TNF-alpha (p<0.01) and increased GSH (p<0.05) levels vs. ET-1. In conclusion, we demonstrated that ET-1 induced oxidative stress in the lungs is mediated by ETA receptors. ETA receptor blockage inhibited generation of free radicals and TNF-alpha and ameliorated antioxidant properties. Moreover, generation of reactive oxygen species is mediated by NOS in the lungs.

• MeSH
• antagonisté endotelinového receptoru farmakologie   terapeutické užití   MeSH
• cyklické peptidy farmakologie   terapeutické užití   MeSH
• endotelin-1 MeSH
• glutathion metabolismus   MeSH
• náhodné rozdělení MeSH
• NG-nitroargininmethylester farmakologie   terapeutické užití   MeSH
• oligopeptidy farmakologie   terapeutické užití   MeSH
• oxidační stres účinky léků   MeSH
• peroxid vodíku metabolismus   MeSH
• peroxidace lipidů účinky léků   MeSH
• piperidiny farmakologie   terapeutické užití   MeSH
• plíce účinky léků   metabolismus   MeSH
• plicní nemoci etiologie   metabolismus   prevence a kontrola   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• receptor endotelinu A metabolismus   MeSH
• receptor endotelinu B metabolismus   MeSH
• synthasa oxidu dusnatého metabolismus   MeSH
• TNF-alfa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antagonisté endotelinového receptoru MeSH
• BQ 788 MeSH Prohlížeč
• cyclo(Trp-Asp-Pro-Val-Leu) MeSH Prohlížeč
• cyklické peptidy MeSH
• endotelin-1 MeSH
• glutathion MeSH
• NG-nitroargininmethylester MeSH
• oligopeptidy MeSH
• peroxid vodíku MeSH
• piperidiny MeSH
• reaktivní formy kyslíku MeSH
• receptor endotelinu A MeSH
• receptor endotelinu B MeSH
• synthasa oxidu dusnatého MeSH
• TNF-alfa MeSH

Chemokine receptors and their chemokine ligands, key mediators of inflammatory and immune cell trafficking, are involved in the regulation of both physiological and pathological processes in the lung. The discovery that chemokine receptors/chemokines, typically expressed by inflammatory and immune cells, are also expressed in structural lung tissue cells suggests their role in mediating the restoration of lung tissue structure and functions. Thus, chemokine receptors/chemokines contribute not only to inflammatory and immune responses in the lung but also play a critical role in the regulation of lung tissue repair, regeneration, and remodeling. This review aims to summarize current state-of-the-art on chemokine receptors and their ligands in lung diseases such as chronic obstructive pulmonary disease, asthma/allergy, pulmonary fibrosis, acute lung injury, and lung infection. Furthermore, the therapeutic opportunities of chemokine receptors in aforementioned lung diseases are discussed. The review also aims to delineate the potential contribution of chemokine receptors to the processes leading to repair/regeneration of the lung tissue.

• Klíčová slova
• asthma, chemokines, chronic obstructive pulmonary disease, infection, injury, lung fibrosis, therapeutics, tissue repair,
• MeSH
• antiflogistika farmakologie   terapeutické užití   MeSH
• cílená molekulární terapie MeSH
• leukocyty fyziologie   MeSH
• lidé MeSH
• plíce imunologie   metabolismus   patologie   MeSH
• plicní nemoci farmakoterapie   imunologie   metabolismus   MeSH
• pohyb buněk MeSH
• receptory chemokinů fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antiflogistika MeSH
• receptory chemokinů MeSH

Proteasomes appear to be involved in the pathophysiology of various acute and chronic lung diseases. Information on the human lung proteasome in health and disease, however, is sparse. Therefore, we studied whether end-stage pulmonary diseases are associated with alterations in lung 20S/26S proteasome content, activity and 20S subunit composition. Biopsies were obtained from donor lungs (n=7) and explanted lungs from patients undergoing lung transplantation because of end stage chronic obstructive pulmonary disease (COPD; n=7), idiopathic pulmonary fibrosis (IPF, n=7) and pulmonary sarcoidosis (n=5). 20S/26S proteasomes in lung extracts were quantified by ELISA, chymotrypsin-like proteasome peptidase activities measured and 20S proteasome beta subunits analyzed by Western blot. As compared with donor lungs, proteasome content was increased in IPF and sarcoidosis, but not in COPD. The relative distribution of free 20S and 26S proteasomes was similar; 20S proteasome was predominant in all extracts. Proteasome peptidase activities in donor and diseased lungs were indistinguishable. All extracts contained a mixed composition of inducible 20S beta immuno-subunits and their constitutive counterparts; a disease associated distribution could not be identified. A higher content of lung proteasomes in IPF and pulmonary sarcoidosis may contribute to the pathophysiology of human fibrotic lung diseases.

• MeSH
• dárci tkání MeSH
• lidé středního věku MeSH
• lidé MeSH
• pilotní projekty MeSH
• plíce metabolismus   MeSH
• plicní nemoci metabolismus   MeSH
• proteasomový endopeptidasový komplex metabolismus   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• proteasomový endopeptidasový komplex MeSH

Exhaled breath condensate is a promising, non-invasive, diagnostic sample obtained by condensation of exhaled breath. Starting from a historical perspective of early attempts of breath testing towards the contemporary state-of-the-art breath analysis, this review article focuses mainly on the progress in determination of non-volatile compounds in exhaled breath condensate. The mechanisms by which the aerosols/droplets of non-volatile compounds are formed in the airways are discussed with methodological consequences for sampling. Dilution of respiratory droplets is a major problem for correct clinical interpretation of the measured data and there is an urgent need for standardization of EBC. This applies also for collection instrumentation and therefore various commercial and in-house built devices are described and compared with regard to their design, function and collection parameters. The analytical techniques and methods for determination of non-volatile compounds as potential markers of oxidative stress and lung inflammation are scrutinized with an emphasis on method suitability, sensitivity and appropriateness. The relevance of clinical findings for each group of possible non-volatile markers of selected pulmonary diseases and methodological recommendations with emphasis on interdisciplinary collaboration that is essential for future development into a fully validated clinical diagnostic tool are given.

• Klíčová slova
• 3-NT, 3-nitrotyrosine, 5-HPETE, 5-LO, 5-hydroperoxyeicosatetraenoic acid, 5-lipoxygenase, 8-IP, 8-isoprostane, ALF, Analytical techniques, BAL, CF, COPD, COX, EBC, Exhaled breath condensate (EBC), FDA, GSH, GSSG, INF-γ, Ions, LT, Metabolites, NMR, PCA, PE, PG, PLS, PLS-DA, PP, PTFE, Proteins, ROS, RS–NO, S-nitrosothiols, SI, TNF-α, U.S. Food and Drug Administration, VOC, airway lining fluid, bronchoalveolar lavage, chronic obstructive pulmonary disease, cyclooxygenase, cystic fibrosis, exhaled breath condensate, glutathione, glutathione disulfide, interferon γ, leukotriene, nuclear magentic resonance, partial least squares, partial least squares discriminant analysis, polyethylene, polypropylene, polytetrafluoroethylene, principal component analysis, prostaglandin, reactive oxygen species, sputum induction, tumor necrosis factor α, volatile organic compounds,
• MeSH
• biologické markery analýza   metabolismus   MeSH
• dechové testy přístrojové vybavení   metody   MeSH
• imunoanalýza MeSH
• lidé MeSH
• plicní nemoci diagnóza   metabolismus   MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• reaktivní formy dusíku analýza   metabolismus   MeSH
• vzduch analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• reaktivní formy dusíku MeSH

Interleukin 17 (IL-17) as one of the pro-inflammatory cytokines is a very important player in the immune response to many pathogens and seems to play a role also in certain chronic and autoimmune diseases. Many studies showing the importance of this cytokine were conducted on murine models and human patients. In recent years, some experiments with other animals in which interleukin-17 was measured were carried out. This review is focused on the findings that have been observed and described in important veterinary species of animals.

• Klíčová slova
• Cattle, Horse, Inflammation, Interleukin-17, Swine,
• MeSH
• autoimunitní nemoci imunologie   veterinární   MeSH
• gastrointestinální trakt imunologie   metabolismus   mikrobiologie   MeSH
• interleukin-17 metabolismus   MeSH
• lidé MeSH
• mléčné žlázy zvířat metabolismus   MeSH
• nemoci kloubů metabolismus   veterinární   MeSH
• plicní nemoci metabolismus   mikrobiologie   veterinární   MeSH
• skot MeSH
• zánět imunologie   veterinární   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• interleukin-17 MeSH

Sensitive assay method was developed for a parallel, rapid and precise determination of the most prominent oxidative stress biomarkers: 8-iso-prostaglandin F(2alpha), malondialdehyde and 4-hydroxynonenal. The method consisted of a pre-treatment part a solid-phase extraction, for rapid and effective isolation of biomarkers from body fluids (exhaled breath condensate, plasma and urine) and the detection method LC-ESI-MS/MS, where the selected reaction monitoring mode was used for its extremely high degree of selectivity and the stable-isotope-dilution assay for its high precision of quantification. The developed method was characterized by the following parameters: the imprecision was below 14.3%, the mean inaccuracy was determined to be lower than 13.1%. The method was tested on samples obtained from patients diagnosed with asbestosis, pleural hyalinosis or silicosis, i.e. occupational lung diseases caused by fibrogenic dusts, inducing oxidative stress in the respiratory system, and then compared to samples from healthy subjects. The difference in concentration levels of biomarkers between the two groups was perceptible in all the body fluids (the difference observed in an exhaled breath condensate was statistically most significant).

• MeSH
• aldehydy analýza   krev   moč   MeSH
• azbest toxicita   MeSH
• biologické markery analýza   krev   moč   MeSH
• dinoprost analogy a deriváty   analýza   krev   moč   MeSH
• extrakce na pevné fázi metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malondialdehyd analýza   krev   moč   MeSH
• oxid křemičitý toxicita   MeSH
• oxidační stres * MeSH
• plicní nemoci krev   etiologie   metabolismus   moč   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• tělesné tekutiny chemie   metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 4-hydroxy-2-nonenal MeSH Prohlížeč
• 8-epi-prostaglandin F2alpha MeSH Prohlížeč
• aldehydy MeSH
• azbest MeSH
• biologické markery MeSH
• dinoprost MeSH
• malondialdehyd MeSH
• oxid křemičitý MeSH

UNLABELLED: The expression of matrix metallo-proteinases (MMP-7 and MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), which are involved in the degradation of the extracellular matrix (ECM) and tumor growth, was investigated in normal lung tissue, tissue of benign pulmonary diseases and non-small cell lung cancer (NSCLC) tissue. PATIENTS AND METHODS: Tumor tissue and surrounding carcinoma-free lung tissue samples were obtained from 91 patients with NSCLC who had undergone surgery in the years 2005-2007 as well as lung tissue from 12 patients operated on for 'benign' bullous emphysema or interstitial lung disease. The mRNA was isolated from the tissues and the expression of mRNA was assessed using a real-time RT PCR method. RESULTS: Significantly higher expression of MMP-7, MMP-9 and TIMP-1 mRNA was demonstrated in the NSCLC tissue in comparison with the normal lung tissue from the same patients (p=0.0003, p<0.0001 and p=0.0018, respectively). Similar results for MMP-7, MMP-9 and TIMP-1 were found in the histological subgroups: squamous cell lung cancer vs. normal tissue (p=0.0198, p=0.0015 and p=0.0366, respectively), and adenocarcinoma vs. normal tissue (p=0.0045, p<0.0001 and p=0.0140, respectively). The expression of MMP-7 was found to be significantly higher in tumor tissue vs. lung tissue of the benign diseases (p=0.0086) and similar results were also recorded in the histological subgroups: squamous cell lung cancer vs. benign tissue (p=0.0171) and adenocarcinoma vs. benign tissue (p=0.0135). The expression of MMP-9 was significantly higher only in the adenocarcinoma subgroup vs. the benign tissue (p=0.0412). No differences in the expression of mRNA between stage IA and stages IB-IIIB of NSCLC were recorded. CONCLUSION: Significantly higher expression of MMP-7 and MMP-9 in tumor tissue than in the surrounding tissue or in benign lung disease tissue supports the notion of an important role of these metalloproteinases in the growth of lung carcinoma. TIMP-1 expression is increased only in carcinoma, but not in benign lung disease.

• MeSH
• lidé MeSH
• matrixová metaloproteinasa 7 genetika   MeSH
• matrixová metaloproteinasa 9 genetika   MeSH
• messenger RNA genetika   MeSH
• nádory plic enzymologie   genetika   metabolismus   MeSH
• nemalobuněčný karcinom plic enzymologie   genetika   metabolismus   MeSH
• plicní nemoci enzymologie   genetika   metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• tkáňový inhibitor metaloproteinasy 1 genetika   MeSH
• tkáňový inhibitor metaloproteinasy 2 genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• matrixová metaloproteinasa 7 MeSH
• matrixová metaloproteinasa 9 MeSH
• messenger RNA MeSH
• tkáňový inhibitor metaloproteinasy 1 MeSH
• tkáňový inhibitor metaloproteinasy 2 MeSH

Neonatal exposure to hyperoxia alters lung development in mice. We tested if retinoic acid (RA) treatment is capable to affect lung development after hyperoxic injury and to maintain structural integrity of lung. The gene of vascular endothelial growth factor A (VEGF-A) is one of the RA-responsive genes. Newborn BALB/c mice were exposed to room air, 40% or 80% hyperoxia for 7 days. One half of animals in each group received 500 mg/kg retinoic acid from day 3 to day 7 of the experiment. At the end of experiment we assessed body weight (BW), lung wet weight (LW), the wet-to-dry lung weight ratio (W/D) and the expression of mRNA for VEGF-A and G3PDH genes. On day 7 the hyperoxia-exposed sham-treated mice (group 80) weighed 20% less than the room air-exposed group, whereas the 80% hyperoxic group treated with RA weighed only 13% less than the normoxic group. W/D values in 80 and 80A groups did not differ, although they both differed from the control group and from 40 groups. There was a significant difference between 40 and 40A groups, but the control group was different from 40 group but not from 40A groups. The 80 and 80A groups had mRNA VEGF-A expression lowered to 64% and 41% of the control group. RA treatment of normoxic and mild hyperoxic groups increased mRNA VEGF-A expression by about 50%. We conclude that the retinoic acid treatment of newborn BALB/c mice exposed for 7 days to 80% hyperoxia reduced the growth retardation in the 80 % hyperoxic group, reduced the W/D ratio in the 40% but not in the 80 % hyperoxic group. Higher VEGF-A mRNA expression in the 80% hyperoxic group treated with RA was not significant compared to the 80% hyperoxic group.

• MeSH
• analýza rozptylu MeSH
• antioxidancia farmakologie   MeSH
• genetická transkripce účinky léků   MeSH
• glyceraldehyd-3-fosfátdehydrogenasy účinky léků   metabolismus   MeSH
• hyperoxie komplikace   metabolismus   patologie   MeSH
• messenger RNA analýza   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• novorozená zvířata MeSH
• plicní alveoly účinky léků   růst a vývoj   metabolismus   patologie   MeSH
• plicní nemoci etiologie   metabolismus   patologie   prevence a kontrola   MeSH
• stupeň závažnosti nemoci MeSH
• tretinoin farmakologie   MeSH
• vaskulární endoteliální růstový faktor A účinky léků   genetika   metabolismus   MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antioxidancia MeSH
• glyceraldehyd-3-fosfátdehydrogenasy MeSH
• messenger RNA MeSH
• tretinoin MeSH
• vaskulární endoteliální růstový faktor A MeSH

Severe burn injuries cause functional impairment in distant internal organs. Although this mechanism is not clear, it is possible that free radical toxicity plays an important role. Research in animals and clinical studies have shown that there is a close relationship between a lipid peroxidative reaction and secondary pathological changes following thermal injury. It has been demonstrated that antioxidant treatment prevents oxidative tissue damage associated with thermal trauma. This study was designed to determine the possible protective effect of caffeic acid phenethyl ester (CAPE) treatment against oxidative damage in the kidney and lung induced by thermal injury. Rats were decapitated either 1, 3 or 7 days after burn injury. CAPE was administered intraperitoneally immediately after thermal injury. Kidney and lung tissues were taken for the determination of malondialdehyde (MDA) level, myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD) and xanthine oxidase (XO) activities. Severe skin thermal injury caused a significant decrease in SOD and CAT activities, as well as significant increases in MDA level, XO and MPO activities in tissues during the postburn period. Treatment of rats with CAPE (10 micromol/kg) significantly elevated the decreased SOD and CAT activities, while it decreased MDA levels and MPO as well as XO activity.

• MeSH
• fenethylalkohol aplikace a dávkování   analogy a deriváty   MeSH
• injekce intraperitoneální MeSH
• krysa rodu Rattus MeSH
• kyseliny kávové aplikace a dávkování   MeSH
• malondialdehyd metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• multiorgánové selhání farmakoterapie   etiologie   metabolismus   MeSH
• nemoci ledvin farmakoterapie   etiologie   metabolismus   MeSH
• oxidoreduktasy metabolismus   MeSH
• plicní nemoci farmakoterapie   etiologie   metabolismus   MeSH
• popálení komplikace   metabolismus   MeSH
• potkani Wistar MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• caffeic acid phenethyl ester MeSH Prohlížeč
• fenethylalkohol MeSH
• kyseliny kávové MeSH
• malondialdehyd MeSH
• oxidoreduktasy MeSH