Long-term methylglyoxal intake aggravates murine Th2-mediated airway eosinophil infiltration

Autor(es)

Medeiros, Matheus L. ^[1] ; de Oliveira, Mariana G. ^[1] ; Tavares, Edith G. ^[1] ; Mello, Glaucia C. ^[1] ; Anhe, Gabriel F. ^[1] ; Monica, Fabiola Z. ^[1] ; Antunes, Edson ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Dept Pharmacol, UNICAMP, Campinas, SP - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: International Immunopharmacology; v. 81, APR 2020.
• Citações Web of Science: 0

Resumo

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/B16 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-kappa B and iNOS whereas COX-2 expression remained unchanged. The high TNF-alpha 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. (AU)

• Processo FAPESP: 17/15175-1 - Modulação da guanilato ciclase solúvel e dos níveis intracelulares de nucleotídeos cíclicos em órgãos do trato urinário inferior e próstata
• Beneficiário: Edson Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Temático