CF Patients’ Airway Epithelium and Sex Contribute to Biosynthesis Defects of Pro-Resolving Lipids

Frontiers in Immunology

Vincent Baillif¹  Marc Dubourdeau¹  Ralph Epaud²  Virginie Escabasse²  Natacha Remus²  Abdolhossein Zare³  Valerie Urbach³  Sadegh Ghorbani-Dalini³  Reginald Philippe³  Agathe Tarze⁴  Khadeeja Adam Sy⁴  Mickael Shum⁴  Maelle Briottet⁴  Charlie M. London⁴ 

[1] Ambiotis, Toulouse, France;Centre Hospitalier Intercommunal de Créteil (CHIC), Créteil, France;Institut National de la Santé Et de la Recherche Médicale (INSERM) U1151 – Institut Necker Enfants Malades (INEM), Paris, France;University Paris Est Créteil, Institut National de la Santé Et de la Recherche Médicale (INSERM) U955, Institut Mondor de Recherche Biomédicale (IMRB), Créteil, France;

关键词: specialized pro-resolving mediators;    cystic fibrosis;    gender specificity;    lipidomics;    resolution of inflammation;   

DOI  :  10.3389/fimmu.2022.915261

来源: DOAJ

【 摘 要 】

Specialized pro-resolving lipid mediators (SPMs) as lipoxins (LX), resolvins (Rv), protectins (PD) and maresins (MaR) promote the resolution of inflammation. We and others previously reported reduced levels of LXA4 in bronchoalveolar lavages from cystic fibrosis (CF) patients. Here, we investigated the role of CF airway epithelium in SPMs biosynthesis, and we evaluated its sex specificity. Human nasal epithelial cells (hNEC) were obtained from women and men with or without CF. Lipids were quantified by mass spectrometry in the culture medium of hNEC grown at air-liquid interface and the expression level and localization of the main enzymes of SPMs biosynthesis were assessed. The 5-HETE, LXA4, LXB4, RvD2, RvD5, PD1 and RvE3 levels were significantly lower in samples derived from CF patients compared with non-CF subjects. Within CF samples, the 12-HETE, 15-HETE, RvD3, RvD4, 17-HODHE and PD1 were significantly lower in samples derived from females. While the mean expression levels of 15-LO, 5-LO and 12-LO do not significantly differ either between CF and non-CF or between female and male samples, the SPMs content correlates with the level of expression of several enzymes involved in SPMs metabolism. In addition, the 5-LO localization significantly differed from cytoplasmic in non-CF to nucleic (or nuclear envelope) in CF hNEC. Our studies provided evidence for lower abilities of airway epithelial cells derived from CF patients and more markedly, females to produce SPMs. These data are consistent with a contribution of CF airway epithelium in the abnormal resolution of inflammation and with worse pulmonary outcomes in women.

【 授权许可】

Unknown