Bile acid profiles are altered in obese individuals with asthma. Thus, we sought to better understand how obesity-related systemic changes contribute to lung pathophysiology. We also test the therapeutic potential of nitro-oleic acid (NO2-OA), a regulator of metabolic and inflammatory signaling pathways, to mitigate allergen and obesity-induced lung function decline in a murine model of asthma. Bile acids were measured in the plasma of healthy subjects and individuals with asthma and serum and lung tissue of mice with and without allergic airway disease (AAD). Lung function, indices of inflammation and hepatic bile acid enzyme expression were measured in obese mice with house dust mite-induced AAD treated with vehicle or NO2-OA. Serum levels of glycocholic acid and glycoursodeoxycholic acid clinically correlate with body mass index and airway hyperreactivity whereas murine levels of β-muricholic acid and tauro-β-muricholic acid were significantly increased and positively correlated with impaired lung function in obese mice with AAD. NO2-OA reduced murine bile acid levels by modulating hepatic expression of bile acid synthesis enzymes, with a concomitant reduction in small airway resistance and tissue elastance. Bile acids correlate to body mass index and lung function decline and the signaling actions of nitroalkenes can limit AAD by modulating bile acid metabolism, revealing a potential pharmacologic approach to improving the current standard of care.

• MeSH
• antiastmatika terapeutické užití   MeSH
• antigeny roztočů domácího prachu toxicita   MeSH
• bronchiální astma farmakoterapie   etiologie   metabolismus   patofyziologie   MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• dospělí MeSH
• dusíkaté sloučeniny terapeutické užití   MeSH
• hubenost MeSH
• játra účinky léků   metabolismus   MeSH
• kyselina glykocholová krev   MeSH
• kyselina ursodeoxycholová analogy a deriváty   krev   MeSH
• kyseliny olejové terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mastné kyseliny chemie   fyziologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• obezita komplikace   metabolismus   patofyziologie   MeSH
• plíce patofyziologie   MeSH
• preklinické hodnocení léčiv MeSH
• respirační alergie chemicky indukované   farmakoterapie   metabolismus   MeSH
• usilovný výdechový objem MeSH
• vitální kapacita MeSH
• žlučové kyseliny a soli metabolismus   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND: The house dust mite (HDM) allergen Der p 18 belongs to the glycoside hydrolase family 18 chitinases. The relevance of Der p 18 for house dust mite allergic patients has only been partly investigated. OBJECTIVE: To perform a detailed characterization of Der p 18 on a molecular, structural and immunological level. METHODS: Der p 18 was expressed in E. coli, purified to homogeneity, tested for chitin-binding activity and its secondary structure was analyzed by circular dichroism. Der p 18-specific IgG antibodies were produced in rabbits to localize the allergen in mites using immunogold electron microscopy and to search for cross-reactive allergens in other allergen sources (i.e. mites, crustacea, mollusca and insects). IgE reactivity of rDer p 18 was tested with sera from clinically well characterized HDM-allergic patients (n = 98) and its allergenic activity was analyzed in basophil activation experiments. RESULTS: Recombinant Der p 18 was expressed and purified as a folded, biologically active protein. It shows weak chitin-binding activity and partial cross-reactivity with Der f 18 from D. farinae but not with proteins from the other tested allergen sources. The allergen was mainly localized in the peritrophic matrix of the HDM gut and to a lower extent in fecal pellets. Der p 18 reacted with IgE from 10% of mite allergic patients from Austria and showed allergenic activity when tested for basophil activation in Der p 18-sensitized patients. CONCLUSION: Der p 18 is a rather genus-specific minor allergen with weak chitin-binding activity but exhibits allergenic activity and therefore should be included in diagnostic test panels for HDM allergy.

• MeSH
• antigeny roztočů domácího prachu chemie   genetika   imunologie   MeSH
• antisérum chemie   MeSH
• bazofily cytologie   účinky léků   imunologie   MeSH
• chitin chemie   imunologie   MeSH
• Escherichia coli genetika   metabolismus   MeSH
• exprese genu MeSH
• interakční proteinové domény a motivy MeSH
• klonování DNA MeSH
• konformace proteinů, alfa-helix MeSH
• konformace proteinů, beta-řetězec MeSH
• králíci MeSH
• lidé MeSH
• proteiny členovců chemie   genetika   imunologie   MeSH
• protilátky krev   chemie   izolace a purifikace   MeSH
• Pyroglyphidae chemie   ultrastruktura   MeSH
• rekombinantní proteiny chemie   genetika   imunologie   MeSH
• respirační alergie chemicky indukované   imunologie   patofyziologie   MeSH
• sbalování proteinů MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• sekvenční seřazení MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The present paper demonstrates by documentary evidence occupational diseases caused by chromium and its compounds. Perforations of the nasal septum were diagnosed in 20 males and 9 females, the last one in 1980. Most of them worked in chromium-plating shops. Other diseases, including bronchial asthma, allergic rhinitis, and contact allergic eczemas, were examined in 1985-1999. Bronchial asthma was reported in a textile dyer who was in contact with chromium dyes for 32 years and two allergic rhinitides (a welder and an electroplater) were reported in 1987 as "other damage to health resulting from work." Out of 103 contact allergic eczemas, only 24 diseases, i.e. less than one quarter, were healed in 1999. Improvements were observed in 59 of them and 20 diseases persist. There was an exceptional finding of a chromium ulcer (pigeonneaux) on the lower extremity of a builder.

• MeSH
• alergická kontaktní dermatitida etiologie   MeSH
• chrom škodlivé účinky   MeSH
• chromany škodlivé účinky   MeSH
• dermatitida z povolání etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci z povolání chemicky indukované   MeSH
• respirační alergie chemicky indukované   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

• MeSH
• antibakteriální látky škodlivé účinky   MeSH
• lidé MeSH
• nemoci ledvin chemicky indukované   MeSH
• nežádoucí účinky léčiv MeSH
• respirační alergie chemicky indukované   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• kazuistiky MeSH