Oxylipin Profiling of Airway Structural Cells Is Unique and Modified by Relevant Stimuli

Overview

Journal J Proteome Res

Publisher American Chemical Society

Specialty Biochemistry

Date 2025 Jan 3

PMID 39752600

Authors

Shana Kahnamoui

Tanja Winter

Dylan Lloyd

Andrew J Halayko

Neeloffer Mookherjee

Harold M Aukema

Christopher D Pascoe

Affiliations

Soon will be listed here.

Abstract

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.

References

Pang L, Knox A . Effect of interleukin-1 beta, tumour necrosis factor-alpha and interferon-gamma on the induction of cyclo-oxygenase-2 in cultured human airway smooth muscle cells. Br J Pharmacol. 1997; 121(3):579-87. PMC: 1564708. DOI: 10.1038/sj.bjp.0701152. View

Gabbs M, Leng S, Devassy J, Monirujjaman M, Aukema H . Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs. Adv Nutr. 2015; 6(5):513-40. PMC: 4561827. DOI: 10.3945/an.114.007732. View

Schaafsma D, McNeill K, Mutawe M, Ghavami S, Unruh H, Jacques E . Simvastatin inhibits TGFβ1-induced fibronectin in human airway fibroblasts. Respir Res. 2011; 12:113. PMC: 3173339. DOI: 10.1186/1465-9921-12-113. View

Gouveia-Figueira S, Karimpour M, Bosson J, Blomberg A, Unosson J, Pourazar J . Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure. Anal Bioanal Chem. 2017; 409(11):2967-2980. PMC: 5366178. DOI: 10.1007/s00216-017-0243-8. View

Sultana C, Shen Y, Rattan V, Kalra V . Lipoxygenase metabolites induced expression of adhesion molecules and transendothelial migration of monocyte-like HL-60 cells is linked to protein kinase C activation. J Cell Physiol. 1996; 167(3):477-87. DOI: 10.1002/(SICI)1097-4652(199606)167:3<477::AID-JCP12>3.0.CO;2-1. View

Ko H, Lin A, Perng D, Lee T, Kou Y . Lung Epithelial TRPA1 Mediates Lipopolysaccharide-Induced Lung Inflammation in Bronchial Epithelial Cells and Mice. Front Physiol. 2020; 11:596314. PMC: 7705107. DOI: 10.3389/fphys.2020.596314. View

Hallenborg P, Jorgensen C, Petersen R, Feddersen S, Araujo P, Markt P . Epidermis-type lipoxygenase 3 regulates adipocyte differentiation and peroxisome proliferator-activated receptor gamma activity. Mol Cell Biol. 2010; 30(16):4077-91. PMC: 2916447. DOI: 10.1128/MCB.01806-08. View

Aukema H, Ravandi A . Factors affecting variability in free oxylipins in mammalian tissues. Curr Opin Clin Nutr Metab Care. 2023; 26(2):91-98. DOI: 10.1097/MCO.0000000000000892. View

Radi Z, Meyerholz D, Ackermann M . Pulmonary cyclooxygenase-1 (COX-1) and COX-2 cellular expression and distribution after respiratory syncytial virus and parainfluenza virus infection. Viral Immunol. 2010; 23(1):43-8. PMC: 2883516. DOI: 10.1089/vim.2009.0042. View

10.

Stebbins K, Broadhead A, Baccei C, Scott J, Truong Y, Coate H . Pharmacological blockade of the DP2 receptor inhibits cigarette smoke-induced inflammation, mucus cell metaplasia, and epithelial hyperplasia in the mouse lung. J Pharmacol Exp Ther. 2009; 332(3):764-75. DOI: 10.1124/jpet.109.161919. View

11.

Sun K, Ma R, Cui X, Campos B, Webster R, Brockman D . Glucocorticoids induce cytosolic phospholipase A2 and prostaglandin H synthase type 2 but not microsomal prostaglandin E synthase (PGES) and cytosolic PGES expression in cultured primary human amnion cells. J Clin Endocrinol Metab. 2003; 88(11):5564-71. DOI: 10.1210/jc.2003-030875. View

12.

Larsson N, Lundstrom S, Pinto R, Rankin G, Karimpour M, Blomberg A . Lipid mediator profiles differ between lung compartments in asthmatic and healthy humans. Eur Respir J. 2013; 43(2):453-63. DOI: 10.1183/09031936.00209412. View

13.

Dodge W, Thomas M . The effect of 5-hydroxyeicosatetraenoic acid on the proliferation of granulocyte progenitors and embryonic fibroblasts of the chick. Biochem Biophys Res Commun. 1985; 131(2):731-5. DOI: 10.1016/0006-291x(85)91299-9. View

14.

Williams J, Czop J, Austen K . Release of leukotrienes by human monocytes on stimulation of their phagocytic receptor for particulate activators. J Immunol. 1984; 132(6):3034-40. View

15.

Mostafa M, Rider C, Shah S, Traves S, Gordon P, Miller-Larsson A . Glucocorticoid-driven transcriptomes in human airway epithelial cells: commonalities, differences and functional insight from cell lines and primary cells. BMC Med Genomics. 2019; 12(1):29. PMC: 6357449. DOI: 10.1186/s12920-018-0467-2. View

16.

Ruan Y, Zhou W, Chan H . Regulation of smooth muscle contraction by the epithelium: role of prostaglandins. Physiology (Bethesda). 2011; 26(3):156-70. DOI: 10.1152/physiol.00036.2010. View

17.

Clarke D, Dakshinamurti S, Larsson A, Ward J, Yamasaki A . Lipid metabolites as regulators of airway smooth muscle function. Pulm Pharmacol Ther. 2008; 22(5):426-35. DOI: 10.1016/j.pupt.2008.12.003. View

18.

Kan M, Koziol-White C, Shumyatcher M, Johnson M, Jester W, Panettieri Jr R . Airway Smooth Muscle-Specific Transcriptomic Signatures of Glucocorticoid Exposure. Am J Respir Cell Mol Biol. 2019; 61(1):110-120. PMC: 6604213. DOI: 10.1165/rcmb.2018-0385OC. View

19.

Relic B, Benoit V, Franchimont N, Ribbens C, Kaiser M, Gillet P . 15-deoxy-delta12,14-prostaglandin J2 inhibits Bay 11-7085-induced sustained extracellular signal-regulated kinase phosphorylation and apoptosis in human articular chondrocytes and synovial fibroblasts. J Biol Chem. 2004; 279(21):22399-403. DOI: 10.1074/jbc.M314118200. View

20.

Kim H, Moon S, Lee S, Hwang G, Yoo H, Song J . The arachidonic acid metabolite 11,12-epoxyeicosatrienoic acid alleviates pulmonary fibrosis. Exp Mol Med. 2021; 53(5):864-874. PMC: 8178404. DOI: 10.1038/s12276-021-00618-7. View