Cytokine secretion requires phosphatidylcholine synthesis

Tian, Yong; Pate, Caroline; Andreolotti, Alberto G.; Wang, Limin; Tuomanen, Elaine; Boyd, Kelli L.; Claro, Enrique; Jackowski, Suzanne

doi:10.1084/jem2057oia17

Cited by 9 publications

(14 citation statements)

References 29 publications

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“…The overexpression of PERK and IRE1a observed in Refeed 1 -supplemented hFM-MSCs may be therefore associated with increased membrane synthesis, reorganization, and trafficking. Membrane biogenesis and reorganization following new lipid uptake may have relevant biomedical implication as shown in macrophages where remodeling of Golgi apparatus promotes transient cytokine synthesis and secretion 89 . We have already shown that Refeed 1 supplementation increases membrane fluidity and plasticity in hFM-MSCs by partially restoring the omega6 fatty acid membrane reservoire 47 .…”

Section: Discussionmentioning

confidence: 99%

Restoring In Vivo-Like Membrane Lipidomics Promotes Exosome Trophic Behavior from Human Placental Mesenchymal Stromal/Stem Cells

et al. 2018

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Human mesenchymal stem cells (hMSCs) are an effective tool in regenerative medicine notably for their intrinsic plentiful paracrine activity rather than differentiating properties. The hMSC secretome includes a wide spectrum of regulatory and trophic factors, encompassing several naked molecules as well as different kinds of extracellular vesicles (EVs). Among EVs, exosomes represent an intriguing population, able to shuttle proteins, transcription factors, and genetic materials, with a relevant role in cell-to-cell communication, modulating biological responses in recipient cells. In this context, the extracellular milieu can greatly impact the paracrine activity of stem cells, modifying their metabolism, and the dynamics of vesicle secretion. In the present study, we investigated the effects elicited on exosome patterning by tailored, ad hoc formulated lipid supplementation (Refeed) in MSCs derived from human fetal membranes (hFM-MSCs). Wound healing experiments revealed that stem cell exposure to exosomes obtained from Refeed-supplemented hFM-MSCs increased their migratory capability, although the amount of exosomes released after Refeed supplementation was lower than that yielded from non-supplemented cells. We found that such a decrease was mainly due to a different rate of exosomal exocytosis rather than to an effect of the lipid supplement on the endocytic pathway. Endoplasmic reticulum homeostasis was modified by supplementation, through the upregulation of PKR-like ER kinase (PERK) and inositol-requiring enzyme 1α (IRE1α). Increased expression of these proteins did not lead to stress-induced, unfolded protein response (UPR)-mediated apoptosis, nor did it affect phosphorylation of p38 kinase, suggesting that PERK and IRE1α overexpression was due to augmented metabolic activities mediated by optimization of a cellular feeding network afforded through lipid supplementation. In summary, these results demonstrate how tailored lipid supplementation can successfully modify the paracrine features in hFM-MSCs, impacting both intracellular vesicle trafficking and secreted exosome number and function.

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Section: Discussionmentioning

confidence: 99%

Restoring In Vivo-Like Membrane Lipidomics Promotes Exosome Trophic Behavior from Human Placental Mesenchymal Stromal/Stem Cells

et al. 2018

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“…As mammalian fatty acid biosynthesis produces predominantly species with 14 to 18 carbons and a low degree of saturation (38), it might be suggested that the observed lipid concentration changes reflect upregulation of endogenous fatty acid biosynthesis and a relative decrease of dietary fatty acid in cellular membranes. Interestingly, in macrophages, PC synthesis has been demonstrated to be prerequisite for cytokine secretion (39).…”

Section: Discussionmentioning

confidence: 99%

T-cell activation induces selective changes of cellular lipidome

Lönnberg

Yetukuri²,

Seppänen‐Laakso³

et al. 2013

Front Biosci

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Activation of naïve T helper cells by presentation of cognate antigen initiates a complex intracellular signaling process leading to development of functionally active effector cell population. The switch from quiescent naïve state to activated state involves a profound change of cellular metabolism, required for completion of multiple rounds of proliferation. Using ultra performance liquid chromatography mass spectrometry, we analyzed how this change is reflected on the cellular lipid composition in human umbilical cord blood T-cells. We found that considerable concentration changes take place during the first 72 hours after T-cell receptor activation, correlating with first rounds of activation-induced cell division. Most importantly, composition of phosphatidylcholines and phosphatidylethanolamines exhibited consistent trend towards shorter and more saturated molecular species. Together with related transcriptomics data, the results clearly suggested induction of de novofatty acid synthesis and accumulation of endogenously synthesized fatty acids into the cellular membranes, leading to partial remodeling of the cellular lipidome in the newly developed effector cell population.

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“…Choline is predominantly used for the synthesis of phosphatidylcholine (PC) in immune cells.Previous experiments have indicated the associations between choline levels and activation of immune cells including macrophages and acutely increased PC synthesis 23,24. Shayne and his colleagues have found that LPS stimulation of macrophages could increase choline uptake and metabolism,25 and limiting the availability of choline could reduce the capacity of pro-inflammatory cytokines secretion 26. Furthermore, Jia's study demonstrated that choline would upregulate the expression of pro-inflammatory factors such as TNF-α and C-reactive protein (CRP), and promote inflammatory response 27.…”

mentioning

confidence: 99%

Circulating choline is associated with coronary artery stenosis in patients with hypertension: A cross‐sectional study of Chinese adults

Guo

Qiu

Zhu

et al. 2020

J of Clinical Hypertension

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Choline is an important nutrient involved in multiple biosynthesis pathways. However, whether circulating choline levels are associated with the risk of hypertension (HTN) and artery stenosis in HTN remains unknown. We investigated the correlations of plasma choline with HTN and coronary artery injury and explored the utility of plasma choline as a diagnostic biomarker for HTN and artery stenosis. 193 HTN patients and 154 age‐ and sex‐matched healthy controls (CON) were recruited in this study. Fasting plasma choline was detected using liquid chromatography tandem mass spectrometry. Choline levels were significantly higher in HTN without artery stenosis (HTN‐AS) than CON (8.07 [7.19‐9.24] μM vs 7.03 [6.21‐8.13] μM, P < .01) group and were further upregulated in HTN with artery stenosis (HTN + AS) (8.63 [7.09‐10.59] μM, P < .01) group. Patients with multivessel disease (MVD) also exhibited higher choline levels than those with single vessel disease (SVD) (8.64 [7.16‐10.55] μM vs 8.04(6.74‐9.38) μM, P < .01). Increased choline levels were independently associated with the risk of HTN (OR = 1.2, 95% CI: 1‐1.45, P = .05), HTN + AS (OR = 1.27, 95% CI: 1.09‐1.48, P < .01), and MVD (OR = 1.16, 95% CI: 1.02‐1.31, P = .02) after adjustment for multiple risk factors. Receiver operating characteristic (ROC) analysis showed that choline had an area under curve (AUC) score of 0.69, 0.67, and 0.63 in determining HTN, HTN + AS, and MVD. In conclusion, higher choline levels were associated with increased risk of HTN and artery stenosis in hypertensive patients.

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Cytokine secretion requires phosphatidylcholine synthesis

Cited by 9 publications

References 29 publications

Restoring In Vivo-Like Membrane Lipidomics Promotes Exosome Trophic Behavior from Human Placental Mesenchymal Stromal/Stem Cells

Restoring In Vivo-Like Membrane Lipidomics Promotes Exosome Trophic Behavior from Human Placental Mesenchymal Stromal/Stem Cells

T-cell activation induces selective changes of cellular lipidome

Circulating choline is associated with coronary artery stenosis in patients with hypertension: A cross‐sectional study of Chinese adults

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