International immunopharmacology, 2020-04, Vol.81, p.106254-106254, Article 106254
2020
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Long-term methylglyoxal intake aggravates murine Th2-mediated airway eosinophil infiltration
- Ist Teil von
- International immunopharmacology, 2020-04, Vol.81, p.106254-106254, Article 106254
- Ort / Verlag
- Netherlands: Elsevier B.V
- Erscheinungsjahr
- 2020
- Quelle
- Elsevier ScienceDirect Journals
- Beschreibungen/Notizen
- •High levels of methylglyoxal (MGO) are found in plasma of prediabetic and diabetic patients.•Long-term MGO intake exacerbated Th2-mediated airway eosinophil infiltration.•MGO activates NF-kB/iNOS-dependent signaling pathway and positive regulation of NOX-2 and NOX-4 in lung tissues.•Scavengers of MGO could be an option to prevent obesity-related asthma. Asthma outcomes is aggravated in obese patients. Excess of methylglyoxal (MGO) in obese/diabetic patients has been associated with diverse detrimental effects on cell function. This study aimed to evaluate the effects of long-term oral intake of MGO on ovalbumin-induced eosinophil inflammation. Male C57/Bl6 mice received 0.5% MGO in the drinking water for 12 weeks. Mice were sensitized and challenged with ovalbumin (OVA), and at 48 h thereafter, bronchoalveolar lavage (BAL) fluid and lungs were collected for cell counting, morphological analysis, and ELISA, mRNA expressions and DHE assays. In MGO-treated mice, OVA challenge significantly increased the peribronchiolar infiltrations of inflammatory cells and eosinophils compared with control group. Higher levels of IL-4, IL-5, and eotaxin in BAL fluid were also detected in MGO compared with control group. In addition, lung tissue of MGO-treated mice displayed significant increases in mRNA expressions of NF-κB and iNOS whereas COX-2 expression remained unchanged. The high TNF-α mRNA expression observed in lungs of OVA-challenged control mice was not further increased by MGO treatment. In MGO group, OVA-challenge increased significantly the NOX-2 and NOX-4 mRNA expressions, without affecting the NOX-1 expression. Levels of reactive-oxygen species (ROS) were significantly higher in lungs of MGO-treated mice, and no further increase by OVA-challenge was observed. In conclusion, 12-week intake of MGO exacerbates Th2-mediated airway eosinophil infiltration by activation of NF-kB/iNOS-dependent signaling pathway and positive regulation of NOX-2 and NOX-4 in the lung tissues. Scavengers of MGO could be an option to prevent obesity-related asthma.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1567-5769eISSN: 1878-1705DOI: 10.1016/j.intimp.2020.106254Titel-ID: cdi_proquest_miscellaneous_2350338461
- Format
- –
- Schlagworte
- Advanced glycated end products, Allergens - immunology, Alveoli, Animal tissues, Animals, Asthma, Asthma - metabolism, Bronchus, Cell activation, Cell Movement, Cyclooxygenase-2, Diabetes mellitus, Disease Models, Animal, Drinking water, Enzyme-linked immunosorbent assay, Eosinophils, Eosinophils - immunology, Eotaxin, Gene expression, Humans, Inducible nitric oxide synthase, Infiltration, Inflammation, Interleukin 4, Interleukin 5, Interleukin-4 - metabolism, Interleukin-5 - metabolism, Leukocytes (eosinophilic), Lungs, Lymphocytes T, Male, Mice, Mice, Inbred C57BL, NADPH Oxidase 4 - genetics, NADPH Oxidase 4 - metabolism, NADPH oxidases, NF-kappa B - metabolism, NF-kB, NF-κB protein, Nitric-oxide synthase, Obesity, Obesity - metabolism, Ovalbumin, Ovalbumin - immunology, Pyruvaldehyde, Pyruvaldehyde - metabolism, Reactive oxygen species, Reactive Oxygen Species - metabolism, Respiratory tract, Signal Transduction, Th2 Cells - immunology, Tumor necrosis factor-α