T Cell-Specific Knockout of STAT3 Ameliorates Dextran Sulfate Sodium-Induced Colitis by Reducing the Inflammatory Response

Kwon, Sun-Ho; Seo, Eun Bi; Lee, Song Hee; Cho, Chung Hyun; Kim, Sung Joon; Kim, Sang Jeong; Kim, Hang Rae; Ye, Sang Kyu

doi:10.4110/in.2018.18.e30

Cited by 17 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Treatment with BDS suspension, KO liposomes, or BDS-entrapped KO liposomes slightly decreased the DSS-induced level of DAI, although statistically not significant (Figure 6A). The colon length was shortened in DSS group, in accordance with the findings of other studies 29,30. BDS or KO liposome treatment slightly but significantly ameliorated DSS-induced colon shortening (Figure 6B).…”

Section: Resultssupporting

confidence: 91%

<p>Krill Oil-Incorporated Liposomes As An Effective Nanovehicle To Ameliorate The Inflammatory Responses Of DSS-Induced Colitis</p>

Kim¹,

Hong²,

Lee³

et al. 2019

IJN

View full text Add to dashboard Cite

BackgroundPhosphatidylcholine (PC) and Omega-3 fatty acid (Omega-3) are promising therapeutic molecules for treating inflammatory bowel disease (IBD).PurposeBased on the IBD therapeutic potential of nanoparticles, we herein sought to develop Omega-3-incorporated PC nanoparticles (liposomes) as an orally administrable vehicle for treating IBD.MethodsLiposomes prepared with or without Omega-3 incorporation were compared in terms of colloidal stability and anitiinflammatory effects.ResultsThe incorporation of free Omega-3 (alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid) into liposomes induced time-dependent membrane fusion, resulting in particle size increase from nm to μm during storage. In contrast, krill oil incorporation into liposomes (KO liposomes) did not induce the fusion and the particle size maintained <250 nm during storage. KO liposomes also maintained colloidal stability in simulated gastrointestinal conditions and exhibited a high capacity to entrap the IBD drug, budesonide (BDS). KO liposomes greatly suppressed the lipopolysaccharide-induced production of pro-inflammatory cytokines in cultured macrophages and completely restored inflammation-impaired membrane barrier function in an intestinal barrier model. In mice subjected to dextran sulfate sodium-induced colitis, oral administration of BDS-entrapped KO liposomes suppressed tumor necrosis factor-α production (by 84.1%), interleukin-6 production (by 35.3%), and the systemic level of endotoxin (by 96.8%), and slightly reduced the macroscopic signs of the disease.ConclusionTaken together, KO liposomes may have great potential as a nanovehicle for oral delivery of IBD drugs.

show abstract

Section: Resultssupporting

confidence: 91%

<p>Krill Oil-Incorporated Liposomes As An Effective Nanovehicle To Ameliorate The Inflammatory Responses Of DSS-Induced Colitis</p>

Kim¹,

Hong²,

Lee³

et al. 2019

IJN

View full text Add to dashboard Cite

show abstract

“…IL-6 augments the expression of STAT3 in the colon, thereafter, regulates the polarization of IEC (Serrano et al, 2019). T cell-specific knockout of STAT3 ameliorates DSS-induced colitis by reducing the inflammatory response (Kwon et al, 2018). In our study, we uncovered that DSS induces the upregulation of STAT3 in the colon along with other inflammatory cytokines including IL-6.…”

Section: Discussionmentioning

confidence: 53%

PDE9 Inhibitor PF-04447943 Attenuates DSS-Induced Colitis by Suppressing Oxidative Stress, Inflammation, and Regulating T-Cell Polarization

Rana

Xue

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Ulcerative colitis (UC) is a form of inflammatory bowel disease, which manifests as irritation or swelling and sores in the large intestine in a relapsing and remitting manner. In a dextran sulfate sodium sulfate (DSS)-induced UC model in female mice, we found that the levels of cyclic guanosine monophosphate (cGMP) are reduced, while the expression of phosphodiesterase 9A (PDE9A) is highest among all phosphodiesterase (PDEs). Since PDE9 has the highest affinity toward cGMP, we evaluated the selective PDE9 inhibitor PF-04447943 (PF) as a potential candidate for UC treatment. PF has been extensively studies in cognitive function and in sickle cell disease, but not in models for inflammatory bowel disease (IBD). Therefore, we used female C57BL/6 mice treated with 3% DSS alone or co-treated with PF or sulfasalazine (SASP) to study the body weight, colon length, histopathology, and measure superoxide dismutase (SOD), malondialdehyde (MDA), and cGMP level, as well as cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-12/23 (IL-12/23), interleukin-10 (IL-10), and pathways including nuclear factor kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and inflammasome activation. In addition, the number of dendritic cells (DC) and regulatory T cells (Treg cell) was assessed in the spleen, lymph node, and colon using flow cytometry. DSS reduced the number of goblet cells, decreased colon lengths and body weights, all of them were attenuated by PF treatment. It also suppressed the elevated level of inflammatory cytokines and increased level the anti-inflammatory cytokine, IL-10. PF treatment also reduced the DSS-induced inflammation by suppressing oxidative stress, NF-κB, STAT3, and inflammasome activation, by upregulating nuclear factor erythroid 2-related factor 2 (Nrf-2) and its downstream proteins via extracellular signal-regulated kinase (ERK) phosphorylation. Importantly, PF reversed imbalance in Treg/T helper 17 cells (Th17) cells ratio, possibly by regulating dendritic cells and Treg developmental process. In summary, this study shows the protective effect of a PDE9A inhibitor in ulcerative colitis by suppressing oxidative stress and inflammation as well as reversing the Treg/Th17 cells imbalance.

show abstract

“…In animal model, we found that LXN deficiency leads to severity of DSS colitis, which can be demonstrated by a number of clinicopathological indicators, including more severe weight loss, hematochezia, shortening of the colon and rectum, damage to the mucosa and loss of goblet cells, increased proinflammatory cytokines and increased STAT3 activity. Many literatures have reported the key role of JAK/STAT3 signal transduction pathway in the pathogenesis of IBD [33][34][35][36] . In the cell model, we prove that ectopic expression of LXN inhibits both basal and TNF-α-induced NF-κB-Luc activity.…”

Section: Discussionmentioning

confidence: 99%

Latexin deficiency in mice up-regulates inflammation and aggravates colitis through HECTD1/Rps3/NF-κB pathway

Huang

Yang

et al. 2020

Sci Rep

View full text Add to dashboard Cite

The function of Latexin (LXN) in inflammation has attracted attention. However, no data are available regarding its role in colitis. We report that LXN is a suppressor of colitis. LXN deficiency leads to the severity of colitis in DSS-induced mice, and LXN is required for the therapeutic effect of retinoic acid on colitis. Using a proteomics approach, we demonstrate that LXN interacts and forms a functional complex with HECTD1 (an E3 ubiquitin ligase) and ribosomal protein subunit3 (Rps3). IκBα is one of the substrates of HECTD1. Ectopic expression of LXN leads to IκBα accumulation in intestinal epithelial cells, however, LXN knockdown enhances the interaction of HECTD1 and Rps3, contributing to the ubiquitination degradation of IκBα, and subsequently enhances inflammatory response. Thus, our findings provided a novel mechanism underlying LXN modulates colitis via HECTD1/Rps3/NF-κB pathway and significant implications for the development of novel strategies for the treatment of colitis by targeting LXN.

show abstract

T Cell-Specific Knockout of STAT3 Ameliorates Dextran Sulfate Sodium-Induced Colitis by Reducing the Inflammatory Response

Cited by 17 publications

References 33 publications

<p>Krill Oil-Incorporated Liposomes As An Effective Nanovehicle To Ameliorate The Inflammatory Responses Of DSS-Induced Colitis</p>

<p>Krill Oil-Incorporated Liposomes As An Effective Nanovehicle To Ameliorate The Inflammatory Responses Of DSS-Induced Colitis</p>

PDE9 Inhibitor PF-04447943 Attenuates DSS-Induced Colitis by Suppressing Oxidative Stress, Inflammation, and Regulating T-Cell Polarization

Latexin deficiency in mice up-regulates inflammation and aggravates colitis through HECTD1/Rps3/NF-κB pathway

Contact Info

Product

Resources

About