FTY720 attenuates intestinal injury and suppresses inflammation in experimental necrotizing enterocolitis via modulating CXCL5/CXCR2 axis

Feng, Zongtai; Zhou, Huiting; Ma, Shu‐Rong; Guan, Xinxian; Chen, Lulu; Huang, Jie; Gui, Huan; Miao, Xinxin; Yu, Shenglin; Wang, Jiang Huai; Wang, Jian

doi:10.1016/j.bbrc.2018.10.013

Cited by 18 publications

(13 citation statements)

References 23 publications

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“…a previous study revealed that excessive inflammation of the immature intestine predisposes premature infants to nec (25). Therefore, elevated levels of il-6 and il-1β may be used as an index of successful nec cell model construction (26)(27)(28). The present results suggested that the expression levels of il-1β, il-6 and Tlr4 in FHcs were significantly increased following lPS exposure, thus indicating that this was a reliable cell model for studying nec in vitro.…”

Section: Discussionsupporting

confidence: 64%

Integrated analysis of a lncRNA‑mRNA network reveals a potential mechanism underlying necrotizing enterocolitis

et al. 2020

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Previous studies have shown that long non-coding rnas (lncrnas) serve important roles in necrotizing enterocolitis (nec). However, the underlying mechanisms remain largely unknown. in order to examine the potential role of lncrnas in nec, the present study investigated lncrna and mRNA expression profiles in NEC lesions and adjacent intestinal tissues using next Generation Sequencing. a total of 4,202 differentially expressed lncrnas (fold-change >2; P<0.05) and 7,860 differentially expressed mrnas (fold-change >2; P<0.05) were identified. Moreover, 5 dysregulated lncrnas and 5 mrnas were randomly selected, and further assessed by reverse transcription-quantitative Pcr in vitro. Gene ontology and Kyoto encyclopedia of Genes and Genomes analyses demonstrated that the differentially expressed lncrnas were closely associated with nec, and were enriched in 'inflammatory response', 'Toll-like receptor binding', 'PPar signaling pathway', 'Pi3K-akt signaling pathway', 'transforming growth factor-β signaling pathway' and 'hypoxia-inducible factor 1 signaling pathway'. in addition, co-expression analysis demonstrated that these lncrnas, including lncrna enST00000623580, lncrna nonHSaT180418.1, lncrna nonHSaT125636.2 and nonHSaT087855.2, may mediate the pathogenesis and development of nec via lncrna-mrna network interactions. Therefore, the present study provided a novel insight into the role of lncrnas in nec.

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Section: Discussionsupporting

confidence: 64%

Integrated analysis of a lncRNA‑mRNA network reveals a potential mechanism underlying necrotizing enterocolitis

et al. 2020

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“…The FICI index indicated a synergistic interaction between AMB and FTY720 (Table 1), which is reported for the first time as far as we know. FTY720 was reported to improve the symptoms of ulcerative colitis (UC) (Feng et al, 2018;Sukocheva et al, 2020). However, the mechanism of its beneficial effects in colitis remains unknown (Danese et al, 2018;Paneś and Salas, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Fingolimod (FTY720) is a S1P receptor inhibitor against several pro-inflammatory conditions including multiple sclerosis (Sukocheva et al, 2020). It can reduce the severity of UC, attenuate intestinal injury, and shows anticancer effects in GI tract (Feng et al, 2018;Sukocheva et al, 2020). When combined with AMB, FTY720 was thus identified to be a promising candidate which exerts a synergistic effect with AMB against the growth of C. albicans.…”

Section: Introductionmentioning

confidence: 99%

Fingolimod Potentiates the Antifungal Activity of Amphotericin B

Wei

Tan

Wang

et al. 2021

Front. Cell. Infect. Microbiol.

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Candida albicans (C. albicans) is an opportunistic human fungal pathogen that can cause severe infection in clinic. Its incidence and mortality rate has been increasing rapidly. Amphotericin B (AMB), the clinical golden standard antifungal agent, has severe side effects that limit its clinical application. Thus, lowering the concentration and increasing the efficacy of AMB in a combinatorial antifungal therapy have been pursued by both industry and academia. Here we identify that fingolimod (FTY720), an immunomodulatory drug used for oral treatment of relapsing-remitting multiple sclerosis, can potentiate the efficacy of AMB against C. albicans growth synergistically. Furthermore, we observe an antifungal efficacy of FTY720 in combination with AMB against diverse fungal pathogens. Intriguingly, cells treated with both drugs are hypersensitive to endothelial endocytosis and macrophage killing. This is later found to be due to the hyperaccumulation of reactive oxygen species and the corresponding increase in activities of superoxide dismutase and catalase in the cells that received combinatorial treatment. Therefore, the combination of AMB and FTY720 provides a promising antifungal strategy.

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“…According to the literature, reductions in proinflammatory cytokines [ 31 , 32 ] and chemokines [ 33 , 34 ] are important indicators for evaluating the regression of inflammation. Thus, the concentrations of proinflammatory cytokines (TNF-α and IL-6) and chemokines (CXCL5) were determined with ELISA kit, and the samples were prepared from the animal wound tissues on day 7.…”

Section: Resultsmentioning

confidence: 99%

Silicone elastomer gel impregnated with 20(S)-protopanaxadiol-loaded nanostructured lipid carriers for ordered diabetic ulcer recovery

Sun

Guo

et al. 2019

Acta Pharmacol Sin

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Inefficient diabetic ulcer healing and scar formation remain a challenge worldwide, owing to a series of disordered and dynamic biological events that occur during the process of healing. A functional wound dressing that is capable of promoting ordered diabetic wound recovery is eagerly anticipated. In this study, we designed a silicone elastomer with embedded 20( S )-protopanaxadiol-loaded nanostructured lipid carriers (PPD-NS) to achieve ordered recovery in scarless diabetic ulcer healing. The nanostructured lipid carriers were prepared through an emulsion evaporation-solidification method and then incorporated into a network of silicone elastomer to form a unique nanostructured lipid carrier-enriched gel formulation. Interestingly, the PPD-NS showed excellent in vitro anti-inflammatory and proangiogenic activity. Moreover, in diabetic mice with full-thickness skin excision wound, treatment with PPD-NS significantly promoted in vivo scarless wound healing through suppressing inflammatory infiltration in the inflammatory phase, promoting angiogenesis during the proliferation phase, and regulating collagen deposition in the remodeling phase. Hence, this study demonstrates that the developed PPD-NS could facilitate ordered diabetic wound recovery via multifunctional improvement during different wound-healing phases. This novel approach could be promising for scarless diabetic wound healing.

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FTY720 attenuates intestinal injury and suppresses inflammation in experimental necrotizing enterocolitis via modulating CXCL5/CXCR2 axis

Cited by 18 publications

References 23 publications

Integrated analysis of a lncRNA‑mRNA network reveals a potential mechanism underlying necrotizing enterocolitis

Integrated analysis of a lncRNA‑mRNA network reveals a potential mechanism underlying necrotizing enterocolitis

Fingolimod Potentiates the Antifungal Activity of Amphotericin B

Silicone elastomer gel impregnated with 20(S)-protopanaxadiol-loaded nanostructured lipid carriers for ordered diabetic ulcer recovery

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