Intestinal anti-inflammatory effects of RGD-functionalized silk fibroin nanoparticles in trinitrobenzenesulfonic acid-induced experimental colitis in rats

Lipocortin 1 is considered a mediator of the anti-inflammatory actions of glucocorticoids. We have shown that this protein is overexpressed and secreted during an experimental colitis induced by intraluminal injection of trinitrobenzenesulfonic acid (TNBS) in rats. We studied here the in vivo regulation of lipocortin 1 expression and secretion in this model, either by glucocorticoids using adrenalectomized or dexamethasone-treated (3 mg/24 h) animals or by pituitary factors using hypophysectomized animals. Inflammation was evaluated by measuring myeloperoxidase activity and by histological scoring of the damage. Lipocortin 1 was detected by immunoblotting, and its secretion was studied by incubating colonic specimens in-culture medium. In the colon of TNBS-injected animals, cumulative histological damage scores were increased in adrenalectomized and decreased in dexamethasone-treated animals compared with control and hypophysectomized animals. The colons of all TNBS-injected animals (controls, adrenalectomized, dexamethasone treated, hypophysectomized) overexpressed and secreted lipocortin 1. In conclusion, the induction of lipocortin 1 overexpression and secretion during this colitis occurs independently of glucocorticoids or pituitary factors.

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Lessons on the Sigma-1 Receptor in TNBS-Induced Rat Colitis: Modulation of the UCHL-1, IL-6 Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms21114046 ◽

2020 ◽

Vol 21 (11) ◽

pp. 4046 ◽

Cited By ~ 1

Author(s):

Nikoletta Almási ◽

Szilvia Török ◽

Szabolcs Dvorácskó ◽

Csaba Tömböly ◽

Ákos Csonka ◽

...

Keyword(s):

Radioligand Binding ◽

Binding Capacity ◽

Treatment Options ◽

Experimental Colitis ◽

Binding Studies ◽

Trinitrobenzenesulfonic Acid ◽

Sigma 1 Receptor ◽

Sigma 1 ◽

Anti Inflammatory ◽

Endothelial Nitric Oxide

Inflammatory Bowel Disease (IBD) is an autoimmune ailment of the gastrointestinal (GI) tract, which is characterized by enhanced activation of proinflammatory cytokines. It is suggested that the sigma-1 receptor (σ1R) confers anti-inflammatory effects. As the exact pathogenesis of IBD is still unknown and treatment options are limited, we aimed to investigate the effects of σ1R in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis. To this end, male Wistar–Harlan rats were used to model colitic inflammation through the administration of TNBS. To investigate the effects of σ1R, Fluvoxamine (FLV, σ1R agonist) and BD1063 (σ1R antagonist) were applied via intracolonic administration to the animals once a day for three days. Our radioligand binding studies indicated the existence of σ1Rs as [3H](+)-pentazocine binding sites, and FLV treatment increased the reduced σ1R maximum binding capacity in TNBS-induced colitis. Furthermore, FLV significantly attenuated the colonic damage, the effect of which was abolished by the administration of BD1063. Additionally, FLV potentially increased the expression of ubiquitin C-terminal hydrolase ligase-1 (UCHL-1) and the levels of endothelial nitric oxide synthase (eNOS), and decreased the levels of interleukin-6 (IL-6) and inducible NOS (iNOS) expression. In summary, our study offers evidence for the anti-inflammatory potential of FLV and σ1R in experimental colitis, and our results present a promising approach to the development of new σ1R-targeted treatment options against IBD.

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Investigation of H2S Donor Treatment on Neutrophil Extracellular Traps in Experimental Colitis

International Journal of Molecular Sciences ◽

10.3390/ijms222312729 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12729

Author(s):

Szilvia Török ◽

Nikoletta Almási ◽

Zsuzsanna Valkusz ◽

Anikó Pósa ◽

Csaba Varga ◽

...

Keyword(s):

High Mobility ◽

Experimental Colitis ◽

Neutrophil Extracellular Traps ◽

Treated Group ◽

Arginine Deiminase ◽

Male Rats ◽

Trinitrobenzenesulfonic Acid ◽

Extracellular Traps ◽

Bowel Diseases ◽

Anti Inflammatory

Inflammatory bowel diseases (IBD) are chronic, immune-mediated disorders, which affect the gastrointestinal tract with intermittent ulceration. It is increasingly clear that neutrophil extracellular traps (NETs) seem to have a role in IBD; however, the associated pathogenesis is still not known. Furthermore, several conventional therapies are available against IBD, although these might have side effects. Our current study aimed to investigate the effects of hydrogen sulfide (H2S) treatment on NETs formation and on the expression of inflammatory mediators in experimental rat colitis. To model IBD, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was administered intracolonically (i.c.) to Wistar–Harlan male rats. Animals were treated (2 times/day) with H2S donor Lawesson’s reagent per os. Our results showed that H2S treatment significantly decreased the extent of colonic lesions. Furthermore, the expression of members of NETs formation: peptidyl arginine deiminase 4 (PAD4), citrullinated histone H3 (citH3), myeloperoxidase (MPO) and inflammatory regulators, such as nuclear transcription factor-kappa B (NF-κB) and high-mobility group box 1 (HMGB1) were reduced in H2S treated group compared to TNBS. Additionally, H2S donor administration elevated the expression of ubiquitin C-terminal hydroxylase L1 (UCHL-1), a potential anti-inflammatory mediator. Taken together, our results showed that H2S may exert anti-inflammatory effect through the inhibition of NETs formation, which suggests a new therapeutic approach against IBD.

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Andrographolide-loaded silk fibroin nanoparticles

RSC Advances ◽

10.1039/c8ra04156c ◽

2018 ◽

Vol 8 (60) ◽

pp. 34726-34732 ◽

Cited By ~ 1

Author(s):

Xu Zhongyu ◽

Ren Jiangmeng ◽

Jing Qiufang ◽

Ren Fuzheng ◽

Huang Mengting ◽

...

Keyword(s):

Silk Fibroin ◽

Biological Activities ◽

Wide Spectrum ◽

Andrographis Paniculata ◽

Silk Fibroin Nanoparticles ◽

Anti Inflammatory

Andrographolide (AP) is a diterpenoid separated from Andrographis paniculata with a wide spectrum of biological activities including anti-inflammatory, anticancer, hepatoprotective, and antihyperlipidemic.

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A comparative study of the preventative effects exerted by two probiotics,Lactobacillus reuteriandLactobacillus fermentum, in the trinitrobenzenesulfonic acid model of rat colitis

British Journal Of Nutrition ◽

10.1017/s0007114507257770 ◽

2007 ◽

Vol 97 (1) ◽

pp. 96-103 ◽

Cited By ~ 99

Author(s):

Laura Peran ◽

Saleta Sierra ◽

Mònica Comalada ◽

Federico Lara-Villoslada ◽

Elvira Bailón ◽

...

Keyword(s):

Lactobacillus Reuteri ◽

Experimental Colitis ◽

No Synthase ◽

Glutathione Depletion ◽

Myeloperoxidase Activity ◽

Trinitrobenzenesulfonic Acid ◽

Beneficial Effects ◽

Colony Forming Units ◽

Inflammatory Bowel ◽

Anti Inflammatory

The intestinal anti-inflammatory effects of two probiotics isolated from breast milk,Lactobacillus reuteriandL. fermentum, were evaluated and compared in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. Colitis was induced in rats by intracolonic administration of 10 mg TNBS dissolved in 50 % ethanol (0·25 ml). EitherL. reuteriorL. fermentumwas daily administered orally (5 × 108colony-forming units suspended in 0·5 ml skimmed milk) to each group of rats (n10) for 3 weeks, starting 2 weeks before colitis induction. Colonic damage was evaluated histologically and biochemically, and the colonic luminal contents were used for bacterial studies and for SCFA production. Both probiotics showed intestinal anti-inflammatory effects in this model of experimental colitis, as evidenced histologically and by a significant reduction of colonic myeloperoxidase activity (P < 0·05).L. fermentumsignificantly counteracted the colonic glutathione depletion induced by the inflammatory process. In addition, both probiotics lowered colonic TNFα levels (P < 0·01) and inducible NO synthase expression when compared with non-treated rats; however, the decrease in colonic cyclo-oxygenase-2 expression was only achieved withL. fermentumadministration. Finally, the two probiotics induced the growth of Lactobacilli species in comparison with control colitic rats, but the production of SCFA in colonic contents was only increased whenL. fermentumwas given. In conclusion,L. fermentumcan exert beneficial immunomodulatory properties in inflammatory bowel disease, being more effective thanL. reuteri, a probiotic with reputed efficacy in promoting beneficial effects on human health.

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Faculty Opinions recommendation of Quercetin-loaded microcapsules ameliorate experimental colitis in mice by anti-inflammatory and antioxidant mechanisms.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718006847.793475963 ◽

2013 ◽

Author(s):

William Gerwick

Keyword(s):

Experimental Colitis ◽

Anti Inflammatory ◽

Antioxidant Mechanisms

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HG-9-91-01 Attenuates Murine Experimental Colitis by Promoting Interleukin-10 Production in Colonic Macrophages Through the SIK/CRTC3 Pathway

Inflammatory Bowel Diseases ◽

10.1093/ibd/izab072 ◽

2021 ◽

Author(s):

Yong Fu ◽

Gailing Ma ◽

Yuqian Zhang ◽

Wenli Wang ◽

Tongguo Shi ◽

...

Keyword(s):

Mononuclear Cells ◽

Experimental Colitis ◽

Underlying Mechanism ◽

Interleukin 10 ◽

Camp Response Element Binding ◽

Cellular Level ◽

Trinitrobenzene Sulfonic Acid ◽

Murine Colitis ◽

Anti Inflammatory

Abstract Background Interleukin-10 (IL-10) is a potent immunoregulatory cytokine that plays a pivotal role in maintaining mucosal immune homeostasis. As a novel synthetic inhibitor of salt-inducible kinases (SIKs), HG-9-91-01 can effectively enhance IL-10 secretion at the cellular level, but its in vivo immunoregulatory effects remain unclear. In this study, we investigated the effects and underlying mechanism of HG-9-91-01 in murine colitis models. Methods The anti-inflammatory effects of HG-9-91-01 were evaluated on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-, dextran sulfate sodium–induced colitis mice, and IL-10 knockout chronic colitis mice. The in vivo effector cell of HG-9-91-01 was identified by fluorescence-activated cell sorting and quantitative real-time polymerase chain reaction. The underlying mechanism of HG-9-91-01 was investigated via overexpressing SIKs in ANA-1 macrophages and TNBS colitis mice. Results Treatment with HG-9-91-01 showed favorable anticolitis effects in both TNBS- and DSS-treated mice through significantly promoting IL-10 expression in colonic macrophages but failed to protect against IL-10 KO murine colitis. Further study indicated that HG-9-91-01 markedly enhanced the nuclear level of cAMP response element-binding protein (CREB)-regulated transcription coactivator 3 (CRTC3), whereas treatment with lentiviruses encoding SIK protein markedly decreased the nuclear CRTC3 level in HG-9-91-01–treated ANA-1 macrophages. In addition, intracolonic administration with lentiviruses encoding SIK protein significantly decreased the nuclear CRTC3 level in the lamina propria mononuclear cells and ended the anti-inflammatory activities of HG-9-91-01. Conclusions We found that HG-9-91-01 promoted the IL-10 expression of colonic macrophages and exhibited its anticolitis activity through the SIK/CRTC3 axis, and thus it may represent a promising strategy for inflammatory bowel disease therapy.

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