Prostaglandin E2 secreted from feline adipose tissue-derived mesenchymal stem cells alleviate DSS-induced colitis by increasing regulatory T cells in mice

An, Ju‐Hyun; Song, Woo‐Jin; Li, Qiang; Kim, Sang-Min; Yang, Jungwook; Ryu, Min-Ok; Nam, Aryung; Bhang, Dong Ha; Jung, Yun-Chan; Youn, Hwa‐Young

doi:10.1186/s12917-018-1684-9

Cited by 43 publications

(36 citation statements)

References 61 publications

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“…In addition, in our previous study, we confirmed the efficacy of adipose-derived stem cells in murinederived macrophage cell lines in inflammatory environments and demonstrated that PGE2 secreted from stem cells is a key factor in polarizing macrophage [50,51]. Moreover, we previous showed that PGE2 secreted feline ASC is a key factor for enhancing regulatory T cell in inflamed colon [52] Although further research on the correlation between these immunomodulatory factors of EV and immune cell regulation is needed, results of the current study confirm that TSG-6-depleted EVs significantly reduce the immunoregulatory ability, which clearly indicates that TSG-6 is a major factor in immune regulation and anti-inflammatory action. Furthermore, the finding that TSG-6 in EVs plays an important role in immune regulation will serve as evidence to support increasing the level of TSG-6 in EVs as a strategy to develop EVs with enhanced immunomodulating properties.…”

Section: Discussionsupporting

confidence: 68%

TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis

Ryu

et al. 2020

PLoS ONE

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Adipose tissue derived mesenchymal stem/stromal cell (ASC)-derived extracellular vesicles (EV) have been reported to be beneficial against dextran sulfate sodium (DSS)-induced colitis in mice. However, the underlying mechanisms have not been fully elucidated. We hypothesize that the tumor necrosis factor-α-stimulated gene/protein 6 (TSG-6) in EVs is a key factor influencing the alleviation of colitis symptoms. DSS-induced colitis mice (C57BL/6, male, Naïve = 6, Sham = 8, PBS = 8 EV = 8, CTL-EV = 8, TSG-6 depleted EV = 8) were intraperitoneally administered EVs (100 ug/mice) on day 1, 3, and 5; colon tissues were collected on day 10 for histopathological, RT-qPCR, western blot and immunofluorescence analyses. In mice injected with EV, inflammation was alleviated. Indeed, EVs regulated the levels of pro-and anti-inflammatory cytokines, such as TNF-α, IL-1β, IFN-γ, IL-6, and IL-10 in inflamed colons. However, when injected with TSG-6 depleted EV, the degree of inflammatory relief was reduced. Furthermore, TSG-6 in EVs plays a key role in increasing regulatory T cells (Tregs) and polarizing macrophage from M1 to M2 in the colon. In conclusion, this study shows that TSG-6 in EVs is a major factor in the relief of DSS-induced colitis, by increasing the number of Tregs and macrophage polarization from M1 to M2 in the colon.

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Section: Discussionsupporting

confidence: 68%

TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis

Ryu

et al. 2020

PLoS ONE

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“…In addition, Benkhoucha et al showed that HGF is a potent immunomodulatory factor that inhibits dendritic cell function along with differentiation of IL-10-producing Tregs 51 . PGE2 alters the cytokine secretion profile of the T cell subset to change from a proinflammatory to an anti-inflammatory environment 52,53 . We confirmed the efficacy of ASC in murine-derived macrophage cell lines in inflammatory environments and demonstrated that PGE2 secreted from stem cells is a key factor in polarizing macrophage 12,54 .…”

Section: Discussionmentioning

confidence: 99%

TNF-α and INF-γ primed canine stem cell-derived extracellular vesicles alleviate experimental murine colitis

Bhang

et al. 2020

Sci Rep

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The inflammatory bowel diseases (IBD) are characterized by relapsing inflammation and immune activation diseases of the gastrointestinal tract. Extracellular vesicles, which elicit similar biological activity to the stem cell themselves, have been used experimentally to treat dextran sulfate sodium (DSS)-induced colitis in murine models though immunosuppressive potential. In this study, we investigated whether the Extracellular vesicles (EVs) obtained by stimulating inflammatory cytokine on canine adipose mesenchymal stem cells (cASC) improved anti-inflammatory and/or immunosuppressive potential of EVs, and/or their ability to alleviate inflammation in colitis. We also explored the correlation between immune cells and the inflammatory repressive effect of primed EVs. Pro-inflammatory cytokines such as TNF-α and ifn-γ increased immunosuppressive protein such as HGF, TSG-6, PGE2 and tGf-β in EVs. Moreover, the anti-inflammatory effect of EVs was improved through pretreatment with inflammatory cytokines. Importantly, EVs obtained from primed stem cells effectively induced macrophage polarization toward an anti-inflammatory M2 phenotype and suppressed activated immunity by enhancing regulatory T cells in inflamed colon in mice. Our results provide a new and effective therapy for the EVs obtained from ASC stimulated with TNF-α and ifn-γ against not only iBD, but also immune-mediated disease.

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“…In general, it is believed that PGE2 is a pro-inflammatory molecule. However, several studies suggest that PGE2 is essential to initiate or trigger anti-inflammatory process [111][112][113].…”

Section: Pge2 and Lxa4 Interact To Induce Resolution Of Inflammationmentioning

confidence: 99%

“Cell Membrane Theory of Senescence” and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications

Das

2021

Biomolecules

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Lipids are an essential constituent of the cell membrane of which polyunsaturated fatty acids (PUFAs) are the most important component. Activation of phospholipase A2 (PLA2) induces the release of PUFAs from the cell membrane that form precursors to both pro- and ant-inflammatory bioactive lipids that participate in several cellular processes. PUFAs GLA (gamma-linolenic acid), DGLA (dihomo-GLA), AA (arachidonic acid), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are derived from dietary linoleic acid (LA) and alpha-linolenic acid (ALA) by the action of desaturases whose activity declines with age. Consequently, aged cells are deficient in GLA, DGLA, AA, AA, EPA and DHA and their metabolites. LA, ALA, AA, EPA and DHA can also be obtained direct from diet and their deficiency (fatty acids) may indicate malnutrition and deficiency of several minerals, trace elements and vitamins some of which are also much needed co-factors for the normal activity of desaturases. In many instances (patients) the plasma and tissue levels of GLA, DGLA, AA, EPA and DHA are low (as seen in patients with hypertension, type 2 diabetes mellitus) but they do not have deficiency of other nutrients. Hence, it is reasonable to consider that the deficiency of GLA, DGLA, AA, EPA and DHA noted in these conditions are due to the decreased activity of desaturases and elongases. PUFAs stimulate SIRT1 through protein kinase A-dependent activation of SIRT1-PGC1α complex and thus, increase rates of fatty acid oxidation and prevent lipid dysregulation associated with aging. SIRT1 activation prevents aging. Of all the SIRTs, SIRT6 is critical for intermediary metabolism and genomic stability. SIRT6-deficient mice show shortened lifespan, defects in DNA repair and have a high incidence of cancer due to oncogene activation. SIRT6 overexpression lowers LDL and triglyceride level, improves glucose tolerance, and increases lifespan of mice in addition to its anti-inflammatory effects at the transcriptional level. PUFAs and their anti-inflammatory metabolites influence the activity of SIRT6 and other SIRTs and thus, bring about their actions on metabolism, inflammation, and genome maintenance. GLA, DGLA, AA, EPA and DHA and prostaglandin E2 (PGE2), lipoxin A4 (LXA4) (pro- and anti-inflammatory metabolites of AA respectively) activate/suppress various SIRTs (SIRt1 SIRT2, SIRT3, SIRT4, SIRT5, SIRT6), PPAR-γ, PARP, p53, SREBP1, intracellular cAMP content, PKA activity and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α). This implies that changes in the metabolism of bioactive lipids as a result of altered activities of desaturases, COX-2 and 5-, 12-, 15-LOX (cyclo-oxygenase and lipoxygenases respectively) may have a critical role in determining cell age and development of several aging associated diseases and genomic stability and gene and oncogene activation. Thus, methods designed to maintain homeostasis of bioactive lipids (GLA, DGLA, AA, EPA, DHA, PGE2, LXA4) may arrest aging process and associated metabolic abnormalities.

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Prostaglandin E2 secreted from feline adipose tissue-derived mesenchymal stem cells alleviate DSS-induced colitis by increasing regulatory T cells in mice

Cited by 43 publications

References 61 publications

TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis

TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis

TNF-α and INF-γ primed canine stem cell-derived extracellular vesicles alleviate experimental murine colitis

“Cell Membrane Theory of Senescence” and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications

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