scholarly journals The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (db/db) Mice

Metabolites ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 26
Author(s):  
Koji Nagao ◽  
Nao Inoue ◽  
Kunio Suzuki ◽  
Takeshi Shimizu ◽  
Teruyoshi Yanagita
Keyword(s):  
Inflammatory Cytokines ◽  
Elevated Serum ◽  
Serum Triglyceride ◽  
Inhibitory Effect ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Abnormal Glucose Metabolism ◽  
Gene Reporter Assay ◽  
Factor Alpha ◽  
Dietary Sterols

Dietary sterols are catabolized into various substances in the intestinal tract. Dietary 3-oxo derivatives of cholesterol and plant sterols (e.g., cholest-4-en-3-one and campest-5-en-3-one) have been shown to have anti-obesity effects. In this study, we tested whether feeding cholest-5-en-3-one (5-cholestenone), a cholesterol metabolite, to db/db mice protects them from obesity-associated metabolic disorders. In db/db mice, dietary 5-cholestenone significantly alleviated hepatomegaly and elevated serum triglyceride levels; however, the effect was not sufficient to improve hepatic steatosis and obesity. On the other hand, hyperglycemia and severe hyperinsulinemia in control db/db mice were markedly attenuated in 5-cholestenone-fed db/db mice. The production of inflammatory cytokines, such as monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-alpha (TNFα), was decreased, suggesting that the suppressive actions of 5-cholestenone were attributable to the alleviation of chronic inflammation in db/db mice. Additionally, 5-cholestenone showed an inhibitory effect on TNFα-induced nuclear factor kappa B (NFκB) activation in the NFκB luciferase gene reporter assay. These results suggest that obesity-induced abnormal glucose metabolism could be alleviated in 5-cholestenone-fed db/db mice by reducing the production of inflammatory cytokines through suppression of the NFκB signaling pathway.

scholarly journals The Aging of Adipocytes Increases Expression of Pro-Inflammatory Cytokines Chronologically

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 292
Author(s):  
Bulbul Ahmed ◽  
Hongwei Si
Keyword(s):  
Adipose Tissue ◽  
Conditioned Medium ◽  
Inflammatory Cytokines ◽  
Inflammatory Markers ◽  
Chow Diet ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Standard Chow Diet ◽  
Factor Alpha ◽  
Pro Inflammatory Cytokines

Adipose tissue is a significant producer of pro-inflammatory cytokines in obese and old individuals. However, there is no direct evidence of whether and how aged adipocytes enhance the production of pro-inflammatory markers. We aimed to investigate whether the aging adipocytes increase pro-inflammatory markers. Swiss mouse embryonic-tissue-derived 3T3-L1 cells were differentiated into adipocytes and maintained for 60 days in the conditioned medium or 35 days in the unconditioned medium. Additionally, 20-month-old male C57BL/6 mice were fed a standard chow diet for 37 weeks until they were extremely aged, when ~75% of mice died because of aging. Accumulated lipids, pro-inflammatory markers, and nuclear factor kappa B (NF-κB) pathway markers from differentiated adipocytes were analyzed. Pro-inflammatory markers and NF-κB pathway markers of epididymal white adipose tissues (EWATs) and adipocytes from EWATs were also analyzed. We found that the aging adipocytes chronologically accumulated lipids and increased pro-inflammatory markers interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α); at the same time, NF-κB p50 markers were also increased while IκBα protein was decreased significantly in conditioned medium. Similar results were observed when differentiated adipocytes were maintained in the unconditioned medium and the adipocytes from EWATs of aged mice. We demonstrated that aging augmented chronic inflammation through the NF-κB signaling pathway in adipocytes and adipose tissue.

Experimental autoimmune encephalomyelitis-induced upregulation of tumor necrosis factor-alpha in the dorsal root ganglia

2009 ◽  
Vol 15 (10) ◽  
pp. 1135-1145 ◽  
Author(s):  
M. Melanson ◽  
P. Miao ◽  
D. Eisenstat ◽  
Y. Gong ◽  
X. Gu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Tumor Necrosis Factor ◽  
Inflammatory Cytokines ◽  
Dorsal Root ◽  
Tumor Necrosis ◽  
Autoimmune Encephalomyelitis ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Experimental Autoimmune

Background: Multiple sclerosis (MS) is a chronic, neurological disease characterized by targeted destruction of central nervous system (CNS) myelin. The autoimmune theory is the most widely accepted explanation of disease pathology. Circulating Th1 cells become activated by exposure to CNS-specific antigens such as myelin basic protein. The activated Th1 cells secrete inflammatory cytokines, which are pivotal for inflammatory responses. We hypothesize that enhanced production of inflammatory cytokines triggers cellular events within the dorsal root ganglia (DRG) and/or spinal cord, facilitating the development of neuropathic pain (NPP) in MS. NPP, the second worst disease-induced symptom suffered by patients with MS, is normally regulated by DRG and/or spinal cord. Objective: To determine gene and protein expression levels of tumor necrosis factor-alpha (TNFα) within DRG and/or spinal cord in an animal model of MS. Methods: Experimental autoimmune encephalomyelitis (EAE) was induced in adolescent female Lewis rats. Animals were sacrificed every 3 days post-disease induction. DRG and spinal cords were harvested for protein and gene expression analysis. Results: We show significant increases in TNFα expression in the DRG and of EAE animals at peak disease stage, as assessed by clinical symptoms. Conclusion: Antigen-induced production of inflammatory cytokines such as TNFα within the DRG identifies a potential novel mechanism for MS-induced NPP.

scholarly journals Profiling of inflammatory cytokines in patients with caustic gastrointestinal tract injury

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260012
Author(s):  
Hao-Tsai Cheng ◽  
Chen-June Seak ◽  
Chien-Cheng Cheng ◽  
Tsung-Hsing Chen ◽  
Chang-Mu Sung ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Inflammatory Cytokines ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Gastrointestinal Complications ◽  
Severe Group ◽  
Factor Alpha ◽  
Necrosis Factor

Introduction Study of inflammatory cytokines in patients with caustic gastrointestinal tract injury is sketchy. This study investigated the cytokine profiling of patients with caustic substance ingestion, and analyzed the differences between patients with severe and mild injury. Methods This prospective, cross-sectional study enrolled 22 patients admitted to Chang Gung Memorial Hospital between March and October 2018. All patients underwent esophagogastroduodenoscopy in 24 hours. Patients were categorized into two subgroups, as mild (<2b, n = 11) or severe (≥2b, n = 11) group. Results The neutrophil count was higher in severe than mild group (P = 0.032). Patients in mild and severe groups exhibited significantly higher circulating inflammatory cytokines than healthy control, including interleukin (IL)-2, IL-5, IL-8, IL-9, IL-12, IL-13, interferon-gamma inducible protein-10, macrophage inflammatory protein-1 beta, regulated upon activation, normal T cell expressed and presumably secreted and tumor necrosis factor-alpha. Furthermore, the levels of IL-2 and tumor necrosis factor-alpha were significantly higher in patients with severe group than mild group. Although there was no difference in cumulative survival between both groups (P = 0.147), the severe group received more operations (P = 0.035) and suffered more gastrointestinal complications (P = 0.035) than mild group. Conclusion Caustic substance ingestion produces mucosal damages and leads to excessive neutrophils and inflammatory cytokines in peripheral blood.

scholarly journals Enzyme Degradation and Proinflammatory Activity in Arthritogenic and Nonarthritogenic Eubacterium aerofaciens Cell Walls

2001 ◽  
Vol 69 (12) ◽  
pp. 7277-7284 ◽  
Author(s):  
Xiang Zhang ◽  
Marja Rimpiläinen ◽  
Egle Šimelyte ◽  
Paavo Toivanen
Keyword(s):  
Proinflammatory Cytokines ◽  
Chronic Arthritis ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Enzyme Degradation ◽  
Tnf Α ◽  
Stimulatory Capacity ◽  
Normal Human ◽  
Proinflammatory Activity ◽  
Factor Alpha

ABSTRACT Two almost-identical strains of Eubacterium aerofaciens isolated from the normal human gut flora were used. The cell wall (CW) of one strain with a peptidoglycan (PG) type A4α induces chronic arthritis in the rat after a single intraperitoneal injection, whereas CW of the other with PG type A4β induces only a transient acute arthritis. The CW of the arthritogenic E. aerofaciens was a twofold-more-potent stimulator of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) than the nonarthritogenic CW. After degradation with mutanolysin, the capacity of the arthritogenic PG to stimulate production of TNF-α and MCP-1 was significantly increased, whereas that of the nonarthritogenic PG was significantly decreased. In other words, after enzyme degradation the arthritogenic PG had a four- to fivefold-stronger stimulatory capacity than that of the enzyme-treated nonarthritogenic PG. These findings indicate that the arthritogenicity of CW or a PG is not dependent on the enzyme resistance alone but also on how the PG fragments released by enzyme degradation stimulate the production of proinflammatory cytokines.

scholarly journals Babesia bovis-Stimulated Macrophages Express Interleukin-1β, Interleukin-12, Tumor Necrosis Factor Alpha, and Nitric Oxide and Inhibit Parasite Replication In Vitro

2000 ◽  
Vol 68 (9) ◽  
pp. 5139-5145 ◽  
Author(s):  
Lisl K. M. Shoda ◽  
Guy H. Palmer ◽  
Jorge Florin-Christensen ◽  
Monica Florin-Christensen ◽  
Dale L. Godson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Cytokines ◽  
Tumor Necrosis ◽  
Acute Infection ◽  
Babesia Bovis ◽  
Necrosis Factor Alpha ◽  
Parasite Replication ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT The tick-transmitted hemoparasite Babesia bovis causes an acute infection that results in persistence and immunity against challenge infection in cattle that control the initial parasitemia. Resolution of acute infection with this protozoal pathogen is believed to be dependent on products of activated macrophages (Mφ), including inflammatory cytokines and nitric oxide (NO) and its derivatives.B. bovis stimulates inducible nitric oxide synthase (iNOS) and production of NO in bovine Mφ, and chemical donors of NO inhibit the growth of B. bovis in vitro. However, the induction of inflammatory cytokines in Mφ by babesial parasites has not been described, and the antiparasitic activity of NO produced by B. bovis-stimulated Mφ has not been definitively demonstrated. We report that monocyte-derived Mφ activated by B. bovisexpressed enhanced levels of inflammatory cytokines interleukin-1β (IL-1β), IL-12, and tumor necrosis factor alpha that are important for stimulating innate and acquired immunity against protozoal pathogens. Furthermore, a lipid fraction of B. bovis-infected erythrocytes stimulated iNOS expression and NO production by Mφ. Cocultures of Mφ and B. bovis-infected erythrocytes either in contact or physically separated resulted in reduced parasite viability. However, NO produced by bovine Mφ in response to B. bovis-infected erythrocytes was only partially responsible for parasite growth inhibition, suggesting that additional factors contribute to the inhibition of B. bovis replication. These findings demonstrate that B. bovis induces an innate immune response that is capable of controlling parasite replication and that could potentially result in host survival and parasite persistence.

Sign in / Sign up

Export Citation Format

Share Document