Kahnamoui Shana, Winter Tanja, Lloyd Dylan, Halayko Andrew J, Mookherjee Neeloffer, Aukema Harold M, Pascoe Christopher D
Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg R3E0J9, Canada.
Biology of Breathing Research Theme, Children's Hospital Research Institute of Manitoba, Winnipeg R3E3P4, Canada.
J Proteome Res. 2025 Feb 7;24(2):672-684. doi: 10.1021/acs.jproteome.4c00775. Epub 2025 Jan 3.
Oxylipins, diverse lipid mediators derived from fatty acids, play key roles in respiratory physiology, but the contribution of lung structural cells to this diverse profile is not well understood. This study aimed to characterize the oxylipin profiles of airway smooth muscle (ASM), lung fibroblasts (HLF), and epithelial (HBE) cells and define how they shift when they are exposed to stimuli related to contractility, fibrosis, and inflammation. Using HPLC-MS/MS, 162 oxylipins were measured in baseline media from cultured human ASM, HLF, and HBE cells as well as after stimulation with modulators of contractility and central regulators of fibrosis/inflammation. At the baseline, ASM and HLF cells had the most similar oxylipin profiles, dominated by oxylipins from cytochrome P450 (CYP450) epoxygenase metabolites. TGFβ stimulation of HLF suppressed CYP450-derived oxylipins, while ASM stimulation increased prostaglandin production. HBE showed the most distinct baseline profile enriched with cyclooxygenase (COX)-derived oxylipins. TGFβ stimulation of HBE increased the level of several oxylipins from CYP450 epoxygenases. These findings highlight the importance of CYP450 oxylipins, which are relatively unexplored in the context of respiratory physiology. By resolving these oxylipin profiles, we enable future respiratory research to understand the function of these oxylipins in regulating physiology, especially in the context of modifying contraction and inflammation.
氧化脂质是一类源自脂肪酸的多种脂质介质，在呼吸生理学中发挥着关键作用，但肺结构细胞对这种多样化特征的贡献尚未得到充分了解。本研究旨在表征气道平滑肌（ASM）、肺成纤维细胞（HLF）和上皮细胞（HBE）的氧化脂质谱，并确定当它们暴露于与收缩性、纤维化和炎症相关的刺激时，这些谱是如何变化的。使用高效液相色谱-串联质谱法（HPLC-MS/MS），在培养的人ASM、HLF和HBE细胞的基础培养基中以及在用收缩性调节剂和纤维化/炎症的中枢调节因子刺激后，测量了162种氧化脂质。在基线时，ASM和HLF细胞的氧化脂质谱最为相似，以细胞色素P450（CYP450）环氧化酶代谢产物的氧化脂质为主。TGFβ对HLF的刺激抑制了CYP450衍生的氧化脂质，而对ASM的刺激增加了前列腺素的产生。HBE显示出最独特的基线谱，富含环氧化酶（COX）衍生的氧化脂质。TGFβ对HBE的刺激增加了几种CYP450环氧化酶衍生的氧化脂质水平。这些发现突出了CYP450氧化脂质的重要性，而在呼吸生理学背景下，它们相对未被充分探索。通过解析这些氧化脂质谱，我们使未来的呼吸研究能够了解这些氧化脂质在调节生理功能中的作用，特别是在调节收缩和炎症方面。
