A probiotic combination attenuates experimental colitis through inhibition of innate cytokine production

2017 ◽  
Vol 8 (2) ◽  
pp. 231-241 ◽  
Author(s):  
M.S. Kim ◽  
J.S. Byun ◽  
Y.S. Yoon ◽  
D.Y. Yum ◽  
M.J. Chung ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Lactobacillus Rhamnosus ◽  
Experimental Colitis ◽  
Intestinal Bleeding ◽  
Myeloperoxidase Activity ◽  
Tissue Destruction ◽  
Raw264.7 Macrophages ◽  
Pro Inflammatory Cytokines

Inflammatory bowel disease (IBD) is a severe immune cell-mediated syndrome characterised by extensive inflammatory and effector mucosal responses leading to tissue destruction in the colon and small intestine. The leading hypothesis is that dysbiosis of the gut flora causes an excessive immune response and inflammation in the gastrointestinal track. Lactic acid bacteria (LAB) can correct dysbiosis of the normal microbiota. In the current study, the therapeutic potential of seven LAB strains in combination to treat IBD was evaluated using experimental colitis model. This LAB cocktail, designated GI7, includes four strains of Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactococcus lactis, two strains of Bifidobacterium bifidum, Bifidobacterium breve, and one strain of Streptococcus thermophilus. We confirmed that GI7 suppressed pro-inflammatory cytokines in Raw264.7 macrophages. When dextran sulphate sodium-induced colitic mice were treated with GI7, their symptoms of colitis, as assessed by body weight, colon length, myeloperoxidase activity, intestinal bleeding, and histological damage, were reduced compared to untreated mice. In addition, GI7 treatment significantly inhibited the production of innate pro-inflammatory cytokines during colitic progression. Therefore, we suggest that GI7, a combination of seven LAB, has a potential role in the treatment of IBD.

scholarly journals Punicalagin Prevents Inflammation in LPS-Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Inflammatory Responses ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Autophagy Inhibition ◽  
Pro Inflammatory Cytokines

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

Abstract 319: Small Molecule Gβγ Inhibition Attenuates Cardiac Fibroblast Inflammatory and Pro-Fibrotic Signaling

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Joshua G Travers ◽  
Fadia A Kamal ◽  
Michael S Burhans ◽  
Burns C Blaxall
Keyword(s):  
Myocardial Fibrosis ◽  
Inflammatory Cytokines ◽  
Small Molecule ◽  
Therapeutic Potential ◽  
Interstitial Fibrosis ◽  
Pressure Overload ◽  
Cardiac Fibroblast ◽  
Ventricular Compliance ◽  
Pro Inflammatory Cytokines

Heart failure (HF) is a devastating disease characterized by chamber remodeling, interstitial fibrosis and reduced ventricular compliance. Prolonged sympathetic overstimulation promotes excess signaling through G-protein Gβγ subunits and ultimately results in pathologic GRK2-mediated β-adrenergic receptor (β-AR) downregulation. We have recently demonstrated the therapeutic potential of the small molecule Gβγ-GRK2 inhibitor Gallein in limiting HF progression. Pathologic activation of the cardiac fibroblast (CF) induces the transition to a myofibroblast phenotype, which plays a fundamental role in myocardial fibrosis and remodeling. We hypothesized that Gβγ-GRK2 inhibition plays an important functional role in the CF to attenuate pathologic CF activation, inflammation and interstitial fibrosis. To explore the effect of Gβγ-GRK2 inhibition on inflammation and pro-fibrotic signaling, mice were subjected to 7 days of transverse aortic constriction, a pressure-overload model of HF. In addition to the attenuation in overall cardiac hypertrophy, animals treated with Gallein displayed reduced expression of pro-inflammatory cytokines, including macrophage inflammatory protein 1 alpha (MIP-1α) and MIP-1β, along with Interleukin-6, as assessed by qPCR. Gallein-treated animals also exhibited diminished pro-fibrotic signaling, as evidenced by a reduction in the expression of TGFβ, a major driver of myocardial fibrosis, and decreased expression of collagen. To recapitulate these findings in vitro, primary adult mouse ventricular fibroblasts were pathologically stimulated using Isoproterenol (ISO, β-AR agonist) or Angiotensin II and treated +/- Gallein for 24 hours. CFs treated with Gallein displayed an analogous reduction in the expression of these pro-inflammatory cytokines and collagen. In summary, these data suggest a potential therapeutic role for small molecule Gβγ-GRK2 inhibition in limiting pathologic myofibroblast activation, inflammation and interstitial fibrosis. We believe this fibroblast-targeted approach will lead to the refinement of existing targets and compounds, and possibly the generation of novel therapeutics for the treatment of HF.

scholarly journals GSK5182, 4-Hydroxytamoxifen Analog, a New Potential Therapeutic Drug for Osteoarthritis

2020 ◽  
Vol 13 (12) ◽  
pp. 429
Author(s):  
Yunhui Min ◽  
Dahye Kim ◽  
Godagama Gamaarachchige Dinesh Suminda ◽  
Xiangyu Zhao ◽  
Mangeun Kim ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Small Molecule ◽  
Articular Chondrocytes ◽  
Therapeutic Potential ◽  
Inverse Agonist ◽  
Therapeutic Drug ◽  
Articular Chondrocyte ◽  
Orphan Nuclear Receptors ◽  
Genetic Ablation ◽  
Pro Inflammatory Cytokines

Estrogen-related receptors (ERRs) are the first identified orphan nuclear receptors. The ERR family consists of ERRα, ERRβ, and ERRγ, regulating diverse isoform-specific functions. We have reported the importance of ERRγ in osteoarthritis (OA) pathogenesis. However, therapeutic approaches with ERRγ against OA associated with inflammatory mechanisms remain limited. Herein, we examined the therapeutic potential of a small-molecule ERRγ inverse agonist, GSK5182 (4-hydroxytamoxifen analog), in OA, to assess the relationship between ERRγ expression and pro-inflammatory cytokines in mouse articular chondrocyte cultures. ERRγ expression increased following chondrocyte exposure to various pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Pro-inflammatory cytokines dose-dependently increased ERRγ protein levels. In mouse articular chondrocytes, adenovirus-mediated ERRγ overexpression upregulated matrix metalloproteinase (MMP)-3 and MMP-13, which participate in cartilage destruction during OA. Adenovirus-mediated ERRγ overexpression in mouse knee joints or ERRγ transgenic mice resulted in OA. In mouse joint tissues, genetic ablation of Esrrg obscured experimental OA. These results indicate that ERRγ is involved in OA pathogenesis. In mouse articular chondrocytes, GSK5182 inhibited pro-inflammatory cytokine-induced catabolic factors. Consistent with the in vitro results, GSK5182 significantly reduced cartilage degeneration in ERRγ-overexpressing mice administered intra-articular Ad-Esrrg. Overall, the ERRγ inverse agonist GSK5182 represents a promising therapeutic small molecule for OA.

scholarly journals Effect of Omega-3 Fatty Acid Rich Oils; Fish Oil and Perilla Oil on High-Fat Diet Fed DSS-Induced Colitis Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1525-1525
Author(s):  
Kyung-Ah Kim ◽  
Shalom Sara Thomas ◽  
Youn-Soo Cha
Keyword(s):  
Fish Oil ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Experimental Colitis ◽  
Normal Diet ◽  
Protective Effects ◽  
Omega 3 ◽  
High Fat ◽  
Perilla Oil ◽  
Pro Inflammatory Cytokines

Abstract Objectives The incidence of inflammatory bowel disease is increasing in newly developing countries, mainly awing to the westernization of the society. Consumption of high-fat diet has known to aggravate colitis. Omega-3 fatty acids are known to have several health benefits including anti-inflammatory effects and some studies have reported the effect of fish oil in experimental colitis. Perilla oil is obtained from the seeds of Perilla frutescens and is known to exert protective effects against obesity, inflammation and hepatic steatosis. We have previously shown that perilla oil has a similar effect like fish oil in high-fat diet induced colon inflammation. In this study, we wanted to investigate the effect fish oil and perilla oil on high-fat-fed, dextran sodium sulfate (DSS)-induced colitis in mice. Methods Six weeks old mice were divided into 4 groups; normal diet without DSS administration (ND), and three high-fat diet with DSS groups; control (HD + DSS), with fish oil supplementation (HDFO+DSS), with perilla oil supplementation (HDPO+DSS). The mice were fed with high-fat diet for 5 weeks prior to DSS administration by water for one week. The mice were sacrificed on the 7th day of DSS administration. Colon length and macroscopic score were measured. The levels of pro-inflammatory cytokines in serum were measured. The stools of the mice were collected for microbial analysis. Results The levels of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β were significantly reduced in FO and PO supplemented groups compared to HD + DSS. The colon length was reduced due to DSS administration compared to ND, and supplementation with FO and PO improved colon length and macroscopic score. Number of Enterobacteriaceae was higher in all DSS administered groups. However, FO and PO treated groups had significantly reduced Enterobacteriaceae. Conclusions The results of this study showed that fish oil and perilla oil exert protective effect against high-fat diet fed DSS-induced colitis. Both fish oil and perilla oil action on colon protection is similar. The experiments to confirm the mechanism of action which includes mRNA and protein analysis are ongoing. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Education).

scholarly journals BMP-7 attenuates adverse cardiac remodeling mediated through M2 macrophages in prediabetic cardiomyopathy

2014 ◽  
Vol 307 (5) ◽  
pp. H762-H772 ◽  
Author(s):  
Princess Urbina ◽  
Dinender K. Singla
Keyword(s):  
Cardiac Function ◽  
Inflammatory Cytokines ◽  
Cardiac Remodeling ◽  
Therapeutic Potential ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Citrate Buffer ◽  
Morphogenetic Protein ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

The main objective of this study was to determine whether or not monocyte infiltration occurs in the prediabetic (PD) heart and its role in PD cardiomyopathy. We hypothesized that the PD heart is significantly populated with monocytes and that bone morphogenetic protein (BMP)-7, a novel mediator of monocyte polarization, activates infiltrated monocytes into anti-inflammatory M2 macrophages, thereby inhibiting apoptosis and fibrosis and improving cardiac function. C57Bl6 mice were assigned to control, PD, or PD + BMP-7 groups. PD and PD + BMP-7 groups were administered streptozotocin (50 mg/kg), whereas control animals received sodium citrate buffer. Afterward, the PD + BMP-7 group was administered BMP-7 (200 μg/kg) for 3 days. Our data showed significantly increased infiltrated monocytes and associated pro-inflammatory cytokines, adverse cardiac remodeling, and heart dysfunction in the PD group ( P < 0.05). Interestingly, M2 macrophage differentiation and associated anti-inflammatory cytokines were enhanced and there were reduced adverse cardiac remodeling and improved cardiac function in the PD + BMP-7 group ( P < 0.05). In conclusion, our data suggest that PD cardiomyopathy is associated with increased monocyte infiltration and released proinflammatory cytokines, which contributes to adverse cardiac remodeling and cardiac dysfunction. Moreover, we report that BMP-7 possesses novel therapeutic potential in its ability to differentiate monocytes into M2 macrophages and confer cardiac protection in the PD heart.

Sign in / Sign up

Export Citation Format

Share Document