Potentiation of indomethacin-induced anti-inflammatory response by pioglitazone in carrageenan-induced acute inflammation in rats: Role of PPARγ receptors

2016 ◽  
Vol 38 ◽  
pp. 434-442 ◽  
Author(s):  
Gholamreza Houshmand ◽  
Mohammad Taghi Mansouri ◽  
Bahareh Naghizadeh ◽  
Ali Asghar Hemmati ◽  
Mahmoud Hashemitabar
Keyword(s):  
Inflammatory Response ◽  
Acute Inflammation ◽  
Anti Inflammatory

Abstract 110: Adiponectin Inhibits TNF-a-Induced Vascular Inflammatory Response via Caveolin-Mediated Ceramidase Recruitment and Activation

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Yajing Wang ◽  
Wayne Lau ◽  
Erhe Gao ◽  
Walter Koch ◽  
Xin Ma
Keyword(s):  
Inflammatory Response ◽  
Protective Action ◽  
Receptor Subtype ◽  
Protective Actions ◽  
Nitrative Stress ◽  
S1p Receptor ◽  
Anti Inflammatory ◽  
Or Gene ◽  
First Time

Anti-inflammatory and vascular protective actions of adiponectin (APN) are well-recognized. However, many fundamental questions remain unanswered. The current study attempted to identify the APN receptor subtype responsible for APN’s vascular protective action, and investigate the role of ceramidase activation in APN anti-inflammatory signaling. Wild type (WT) or gene manipulated HUVEC were treated with TNFα in the presence and absence of APN. The effect of APN on TNFα-induced inflammatory and oxidative/nitrative stress was determined. In WT HUVEC, APN significantly reduced TNFα-induced ICAM-1 expression and attenuated TNFα-induced superoxide and peroxynitrite formation (P<0.01). These anti-inflammatory actions were virtually abolished by AdipoR1-, but not AdipoR2-, knockdown (KD). Treatment with APN significantly increased neutral ceramidase (nCDase) activity (3.7-fold, P<0.01). AdipoR1-KD markedly (P0.05), reduced APN-induced nCDase activation. More importantly, siRNA mediated nCDase-KD markedly blocked the effect of APN upon TNFα-induced ICAM-1 expression (P0.05), and modestly inhibited APN anti-inflammatory effect (P87% of APN-induced nCDase activation was lost. Whereas APN treatment failed to inhibit TNFα-induced ICAM-1 expression, treatment with S1P or SEW (S1P receptor agonist) remained effective in Cav1-KD cells in reducing TNFα-induced ICAM-1 expression (P<0.01). AdipoR1 and Cav1 co-localized and co-precipitated in HUVECs. APN treatment did not affect this interaction. Moreover, re-expression of WT Cav1 in Cav1-KD cells restored nCDase activation in response to APN (P<0.01 vs. vehicle), whereas re-expression of a mutated Cav1 blocking AdipoR1/Cav1 interaction failed to restore APN-mediated nCDase activation. Finally, there is weak basal Cav1/nCDase interaction, which significantly increased following APN treatment. These results demonstrate for the first time that APN inhibits TNFα-induced inflammatory response via Cav1-mediated ceramidase recruitment and activation in an AdipoR1- dependent fashion.

scholarly journals Computational modelling of the inflammatory response in trauma, sepsis and wound healing: implications for modelling resilience

2014 ◽  
Vol 4 (5) ◽  
pp. 20140004 ◽  
Author(s):  
Yoram Vodovotz
Keyword(s):  
Inflammatory Response ◽  
Acute Inflammation ◽  
Computational Modelling ◽  
Data Driven ◽  
Patient Specific ◽  
Cell Tissue ◽  
Organ Systems ◽  
Forward Process

Resilience refers to the ability to recover from illness or adversity. At the cell, tissue, organ and whole-organism levels, the response to perturbations such as infections and injury involves the acute inflammatory response, which in turn is connected to and controlled by changes in physiology across all organ systems. When coordinated properly, inflammation can lead to the clearance of infection and healing of damaged tissues. However, when either overly or insufficiently robust, inflammation can drive further cell stress, tissue damage, organ dysfunction and death through a feed-forward process of inflammation → damage → inflammation. To address this complexity, we have obtained extensive datasets regarding the dynamics of inflammation in cells, animals and patients, and created data-driven and mechanistic computational simulations of inflammation and its recursive effects on tissue, organ and whole-organism (patho)physiology. Through this approach, we have discerned key regulatory mechanisms, recapitulated in silico key features of clinical trials for acute inflammation and captured diverse, patient-specific outcomes. These insights may allow for the determination of individual-specific tolerances to illness and adversity, thereby defining the role of inflammation in resilience.

scholarly journals α-Linolenic acid induces clearance of Tau seed via Actin-remodeling in Microglia

2020 ◽  
Author(s):  
Smita Eknath Desale ◽  
Subashchandrabose Chinnathambi
Keyword(s):  
Fatty Acids ◽  
Inflammatory Response ◽  
Dietary Supplement ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Cellular Functions ◽  
Actin Remodeling ◽  
Membrane Ruffling ◽  
Anti Inflammatory

Abstract Background Tau seeds exhibit a detrimental role in the spread of disease in Alzheimer’s disease. These species are found to be neurotoxic and activate microglia. However, the activation of microglia in pro-inflammatory response further elevates neurodegeneration. Omega-3 dietary fatty acids, on the other hand; exert an anti-inflammatory response by microglia. Along with the receptor expression, omega-3 fatty acids influence various important cellular functions. The role of omega-3 fatty acids on actin remodeling, which is the basis of cellular functions such as migration and phagocytosis is not known. Here in this study, we focus on effect of dietary supplement of ALA on extracellular Tau internalization and assisted actin polymerization for the process. ALA is found to induce membrane ruffling and phagocytic cup formation along with cytoskeletal rearrangement to induce lamellipodia and filopodia at the front end to move forward and assist the cell to identify the target. ALA is observed to promote the internalization of Tau and necessary actin remodeling for phagocytosis. Methods α-Linolenic (ALA) acid has been used for the study. ALA was dissolved in 100% ethanol and solubilized at 50°C for 2 hours. The human Tau aggregates was prepared in vitro for the internalization study in microglia in presence of α-Linolenic acids (ALA) via fluorescence microscopy with Apotome. The studied the role α-Linolenic acids (ALA) actin remodeling in cellular processes in presence of Tau seed. The study of actin structures lamellipodia, filopodia, and membrane ruffling along with Iba-1 and Arp2/3 complex was observed on ALA exposure. Results Extracellular Tau species are found to internalize more presence of ALA in microglia. The extensive polarization and migration was observed as indicated by extensive lamellipodia and filopodia formation. The formation of extensive actin branching in lamellipodia and membrane ruffling was studied with the help of ARP2/3 complex for nucleating actin network. The high density of ARP2/3 complex at the leading ends of migratory microglia confirmed the extensive branching of actin filaments on ALA exposure. Enhanced formation of lamellipodia and filopodia helps in migration and internalization of tau seed. The actin dynamics supports the phagocytosis process. Conclusion Our approach provides the insights of beneficial role of ALA as anti-inflammatory dietary supplement to treat AD. ALA induces internalization of Tau and necessary actin remodeling for phagocytosis.

scholarly journals The role of progranulin (PGRN) in the modulation of anti-inflammatory response in asthma

2019 ◽  
Vol 44 (1) ◽  
pp. 91-101
Author(s):  
Milena Pogonowska ◽  
Łukasz A. Poniatowski ◽  
Agata Wawrzyniak ◽  
Katarzyna Królikowska ◽  
Bolesław Kalicki
Keyword(s):  
Inflammatory Response ◽  
Anti Inflammatory

scholarly journals Anti-inflammatory protein TNFα-stimulated gene-6 (TSG-6) reduces inflammatory response after brain injury in mice

2020 ◽  
Author(s):  
Kazadi Nadine Mutoji ◽  
Mingxia Sun ◽  
Amanda Nash ◽  
Sudan Puri ◽  
Vincent Hascall ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Brain Injuries ◽  
Glial Scar ◽  
Littermate Control ◽  
Puncture Wound ◽  
Injury Site ◽  
Inflammatory Protein ◽  
Anti Inflammatory ◽  
Necrosis Factor

Abstract Background: Current research suggests that the glial scar surrounding penetrating brain injuries is instrumental in preserving the surrounding uninjured tissue by limiting the inflammatory response to the injury site. We recently showed that tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6), a well-established anti-inflammatory molecule, is present within the glial scar. We hereby investigate the role of TSG-6 within the glial scar.Methods: TSG-6 null and littermate control mice were subjected to penetrating brain injuries (2 mm puncture wound to the frontal cortex), after which both the injury site and remaining injured hemisphere were analyzed. The presence of activated astrocytes, inflammatory markers and glial scar components was evaluated by real-time PCR and immunofluorescence. Results: Our findings show that mice lacking TSG-6 present a more severe inflammatory response after injury, which is correlated with an enlarged area of astrogliosis beyond the injury site.Conclusion: Our data provides evidence that TSG-6 has an anti-inflammatory role within the glial scar.

scholarly journals Celiac Disease in Children, Particularly with Accompanying Type 1 Diabetes, Is Characterized by Substantial Changes in the Blood Cytokine Balance, Which May Reflect Inflammatory Processes in the Small Intestinal Mucosa

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Tamara Vorobjova ◽  
Aili Tagoma ◽  
Astrid Oras ◽  
Kristi Alnek ◽  
Kalle Kisand ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Celiac Disease ◽  
Small Bowel ◽  
Inflammatory Response ◽  
Lamina Propria ◽  
Small Bowel Mucosa ◽  
Anti Inflammatory ◽  
Bowel Mucosa

Cytokines play a pivotal role in the maintenance of intestinal homeostasis inducing pro- or anti-inflammatory response and mucosal barrier function in celiac disease (CD) and type 1 diabetes (T1D). We aimed to compare the levels of pro- and anti-inflammatory cytokines in CD patients without and with coexisting T1D, as well as to evaluate its association with the presence of enteroviruses (EV), regulatory T cells (Tregs), and dendritic cells (DCs) in small bowel mucosa. Altogether, 72 patients (median age 10.1 years) who had undergone small bowel biopsy were studied. The study group consisted of 24 patients with CD (median age 6.5 years), 9 patients with CD and concomitant T1D (median age 7.0 years), two patients with T1D (median age 8.5 years), and 37 patients (median age 14.0 years) with functional gastrointestinal disorders (FGD) and a normal small bowel mucosa as controls. The levels of 33 cytokines in serum were measured by multiple analysis using the Milliplex® MAP Magnetic Bead assay. The densities of FOXP3+ Tregs, CD11c+ DC, indoleamine 2,3-dioxygenase+ (IDO+) DC, langerin+ (CD207+) DCs, and EV were evaluated by immunohistochemistry as described in our previous studies. Circulating anti-EV IgA and IgG were evaluated using ELISA. The most important finding of the study is the significant increase of the serum levels of IL-5, IL-8, IL-13, IL-15, IL-17F, IL-22, IL-27, IP-10, MIP-1β, sIL-2Rα, sTNFRII, and TNFαin CD patients compared to controls and its correlation with the degree of small bowel mucosa damage graded according to the Marsh classification. The leptin level was higher in females in all study groups. The levels of IL-2, IL-6, IL-12 (P70), IL-15, IP-10, and IFNγcorrelated significantly with the density of FOXP3+ Tregs inlamina propriaof the small bowel mucosa, which supports the evidence about the signaling role of these cytokines in the peripheral maintenance of FOXP3+ Tregs. At the same time, a significant negative correlation occurred between the level of IL-4 and density of FOXP3+ Tregs in controls. Another important finding of our study was the correlation of IL-17F, IP-10, sTNFRII, MCP-1, and GM-CSF with the density of EV-positive cells in thelamina propriaof the small bowel mucosa. Correlation of MIP-1 (CCL-4) with CD103+ DC and langerin+ DC densities may point to their significance in the recruitment of immune cells into thelamina propriaand in driving the inflammatory response in CD patients. Our results suggest the predominance of Th1 and Th17 immune responses over EV VP1 protein in CD and T1D patients. The significant elevation of Th2 cytokines, like IL-5 and IL-13, but not IL-4, in CD patients and its correlation with the degree of small bowel mucosa damage could reflect the role of these cytokines in gut defense and inflammation.

scholarly journals Participation of the adrenal gland in the anti-inflammatory effect of polyunsaturated diets

1995 ◽  
Vol 4 (5) ◽  
pp. 359-363 ◽  
Author(s):  
V. L. F. Silveira ◽  
E. A. Limãos ◽  
D. W. Nunes
Keyword(s):  
Fatty Acid ◽  
Adrenal Gland ◽  
Inflammatory Response ◽  
Significant Inhibition ◽  
Carrageenin Oedema ◽  
Paw Oedema ◽  
Anti Inflammatory ◽  
Carrageenin Injection ◽  
Inflammatory Effect

The effect of an n-3 (fish) and n-6 (soybean) fatty acid-rich diet on carrageenin paw oedema in rats, and the participation of adrenal gland, corticosterone and α2-macroglobulin (α2-M) in this process were studied. A significant inhibition of carrageenin oedema was observed not only in rats fed a diet rich in fish oil but also in the soybean group. α2-M was not detectable before carrageenin injection, suggesting that this putative antiinflammatory factor does not participate in the observed anti-inflammatory effect. Corticosterone levels were higher in fat-fed than in control rats, before carrageenin stimulus and adrenalectomy abolished the anti-inflammatory response in fat-fed animals, showing the important role of the adrenocortical hormones in this process.

scholarly journals Anti-inflammatory protein TNFα-stimulated gene-6 (TSG-6) reduces inflammatory response after brain injury in mice

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kazadi Nadine Mutoji ◽  
Mingxia Sun ◽  
Amanda Nash ◽  
Sudan Puri ◽  
Vincent Hascall ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Tumor Necrosis ◽  
Brain Injuries ◽  
Glial Scar ◽  
Littermate Control ◽  
Injury Site ◽  
Inflammatory Protein ◽  
Anti Inflammatory ◽  
Necrosis Factor

Abstract Background Current research suggests that the glial scar surrounding penetrating brain injuries is instrumental in preserving the surrounding uninjured tissue by limiting the inflammatory response to the injury site. We recently showed that tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6), a well-established anti-inflammatory molecule, is present within the glial scar. In the present study we investigated the role of TSG-6 within the glial scar using TSG-6 null and littermate control mice subjected to penetrating brain injuries. Results Our findings show that mice lacking TSG-6 present a more severe inflammatory response after injury, which was correlated with an enlarged area of astrogliosis beyond the injury site. Conclusion Our data provides evidence that TSG-6 has an anti-inflammatory role within the glial scar.

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