作者: Larissa Bazela Maschio-Signorini ; Gabriela Bottaro Gelaleti ; Thaiz Ferraz Borin ; Debora Aparecida Pires de Campos Zuccari ; Guilherme Berto Calvinho ; Alicia M. Viloria-Petit ; Bruna Victorasso Jardim-Perassi ; Marina Gobbe Moschetta ; Mariana Castilho Facchini

Mammary tumorigenesis can be modulated by melatonin, which has oncostatic action mediated by multiple mechanisms, including the inhibition of the activity of transcription factors such as NF-κB and modulation of interleukins (ILs) expression. IL-25 is an active cytokine that induces apoptosis in tumor cells due to differential expression of its receptor (IL-17RB). IL-17B competes with IL-25 for binding to IL-17RB in tumor cells, promoting tumorigenesis. This study purpose is to address the possibility of engaging IL-25/IL-17RB signaling to enhance the effect of melatonin on breast cancer cells. Breast cancer cell lines were cultured monolayers and 3D structures and treated with melatonin, IL-25, siIL-17B, each alone or in combination. Cell viability, gene and protein expression of caspase-3, cleaved caspase-3 and VEGF-A were performed by qPCR and immunofluorescence. In addition, an apoptosis membrane array was performed in metastatic cells. Treatments with melatonin and IL-25 significantly reduced tumor cells viability at 1mM and 1ng/mL, respectively, but did not alter cell viability of a non-tumorigenic epithelial cell line (MCF-10A). All treatments, alone and combined, significantly increased cleaved caspase-3 in tumor cells grown as monolayers and 3D structures (p<0.05). Semi-quantitative analysis of apoptosis pathway proteins showed an increase of CYTO-C, DR6, IGFBP-3, IGFBP-5, IGFPB-6, IGF-1, IGF-1R, Livin, P21, P53, TNFRII, XIAP and hTRA proteins and reduction of caspase-3 (p<0.05) after melatonin treatment. All treatments reduced VEGF-A protein expression in tumor cells (p<0.05). Our results suggest therapeutic potential, with oncostatic effectiveness, pro-apoptotic and anti-angiogenic properties for melatonin and IL-25-driven signaling in breast cancer cells.

2016-06-01·International Journal of Biological Macromolecules1区 · 化学

Venom peptides cathelicidin and lycotoxin cause strong inhibition of Escherichia coli ATP synthase

1区 · 化学

Article

作者: Alec Cartagena ; Zulfiqar Ahmad ; Sofiya Azim ; Ricky Rodriguez ; Thomas F. Laughlin ; Derek McDowell

Venom peptides are known to have strong antimicrobial activity and anticancer properties. King cobra cathelicidin or OH-CATH (KF-34), banded krait cathelicidin (BF-30), wolf spider lycotoxin I (IL-25), and wolf spider lycotoxin II (KE-27) venom peptides were found to strongly inhibit Escherichia coli membrane bound F1Fo ATP synthase. The potent inhibition of wild-type E. coli in comparison to the partial inhibition of null E. coli by KF-34, BF-30, Il-25, or KE-27 clearly links the bactericidal properties of these venom peptides to the binding and inhibition of ATP synthase along with the possibility of other inhibitory targets. The four venom peptides KF-34, BF-30, IL-25, and KE-27, caused ≥85% inhibition of wild-type membrane bound E.coli ATP synthase. Venom peptide induced inhibition of ATP synthase and the strong abrogation of wild-type E. coli cell growth in the presence of venom peptides demonstrates that ATP synthase is a potent membrane bound molecular target for venom peptides. Furthermore, the process of inhibition was found to be fully reversible.

2014-02-01·Annals of Surgery1区 · 医学

IL-25 Improves Luminal Innate Immunity and Barrier Function During Parenteral Nutrition

1区 · 医学

Article

作者: Joseph F Pierre ; Ankush Gosain ; Kenneth A Kudsk ; Aaron F Heneghan

BACKGROUNDParenteral nutrition (PN) increases risks of infections in critically injured patients. Recently, PN was shown to reduce intestine luminal levels of the Paneth cell antimicrobial molecule secretory phospholipase A2 (sPLA2) and the goblet cell glycoprotein mucin2 (MUC2). These molecules are critical factors for innate mucosal immunity and provide barrier protection. Interleukin-4 (IL-4) and IL-13 regulate sPLA2 and MUC2 production through the IL-13 receptor. Because IL-25 stimulates IL-4 and IL-13 release and PN reduces luminal sPLA2 and MUC2, we hypothesized that adding IL-25 to PN would restore these innate immune factors and maintain barrier function.METHODSTwo days after venous cannulation, male ICR (Institute of Cancer Research) mice were randomized to receive chow (n = 12), PN (n = 9), or PN + 0.7 μg of exogenous IL-25 (n = 11) daily for 5 days. Small-intestine wash fluid (SIWF) was collected for analysis of sPLA2 activity, MUC2 density, and luminal levels of IL-4 and IL-13. Small-intestinal tissue was harvested for analysis of tissue sPLA2 activity or immediate use in an ex-vivo intestinal segment culture (EVISC) to assess susceptibility of the tissue segments to enteroinvasive Escherichia coli.RESULTSPN reduced luminal sPLA2 (P < 0.0001) and MUC2 (P <0.002) compared with chow, whereas the addition of IL-25 to PN increased luminal sPLA2 (P < 0.0001) and MUC2 (P < 0.02) compared with PN. Tissue IL-4 and IL-13 decreased with PN compared with chow (IL-4: P < 0.0001, IL-13: P < 0.002), whereas IL-25 increased both cytokines compared with PN (IL-4: P < 0.03, IL-13: P < 0.02). Tissue levels of sPLA2 were significantly decreased with PN compared with chow, whereas IL-25 significantly increased tissue sPLA2 levels compared with PN alone. Functionally, more bacteria invaded the PN-treated tissue compared with chow (P < 0.01), and the addition of IL-25 to PN decreased enteroinvasion to chow levels (P < 0.01).CONCLUSIONSPN impairs innate mucosal immunity by suppressing luminal sPLA2 activity and MUC2 density compared with chow. PN also increases bacterial invasion in ex-vivo tissue. Administration of exogenous IL-25 reverses this dysfunction and increases luminal sPLA2 and MUC2. PN tissue treated with IL-25 was significantly more resistant to bacterial invasion than with PN alone, suggesting that IL-25-induced effects augment the barrier defense mechanisms.

100 项与 IL-25 (University of Maryland Baltimore County) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
代谢性疾病	临床前	美国	University of Maryland Baltimore County	-
代谢性疾病	临床前	美国	Um Ventures Pvt Ltd.	-
肥胖	临床前	美国	Um Ventures Pvt Ltd.	-
肥胖	临床前	美国	University of Maryland Baltimore County	-