scholarly journals DGLA from the Microalga Lobosphaera Incsa P127 Modulates Inflammatory Response, Inhibits iNOS Expression and Alleviates NO Secretion in RAW264.7 Murine Macrophages

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2892
Author(s):  
Ekaterina Novichkova ◽  
Katya Chumin ◽  
Noy Eretz-Kdosha ◽  
Sammy Boussiba ◽  
Jacob Gopas ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Inflammatory Response ◽  
Free Acid ◽  
Acid Ethyl Ester ◽  
Ethyl Esters ◽  
Immune Reactivity ◽  
Necrosis Factor Alpha ◽  
Enhanced Production ◽  
Anti Inflammatory ◽  
Delta 5 Desaturase

Microalgae have been considered as a renewable source of nutritional, cosmetic and pharmaceutical compounds. The ability to produce health-beneficial long-chain polyunsaturated fatty acids (LC-PUFA) is of high interest. LC-PUFA and their metabolic lipid mediators, modulate key inflammatory pathways in numerous models. In particular, the metabolism of arachidonic acid under inflammatory challenge influences the immune reactivity of macrophages. However, less is known about another omega-6 LC-PUFA, dihomo-γ-linolenic acid (DGLA), which exhibits potent anti-inflammatory activities, which contrast with its delta-5 desaturase product, arachidonic acid (ARA). In this work, we examined whether administrating DGLA would modulate the inflammatory response in the RAW264.7 murine macrophage cell line. DGLA was applied for 24 h in the forms of carboxylic (free) acid, ethyl ester, and ethyl esters obtained from the DGLA-accumulating delta-5 desaturase mutant strain P127 of the green microalga Lobosphaera incisa. DGLA induced a dose-dependent increase in the RAW264.7 cells’ basal secretion of the prostaglandin PGE1. Upon bacterial lipopolysaccharide (LPS) stimuli, the enhanced production of pro-inflammatory cytokines, tumor necrosis factor alpha (TNFα) and interleukin 1β (IL-1β), was affected little by DGLA, while interleukin 6 (IL-6), nitric oxide, and total reactive oxygen species (ROS) decreased significantly. DGLA administered at 100 µM in all forms attenuated the LPS-induced expression of the key inflammatory genes in a concerted manner, in particular iNOS, IL-6, and LxR, in the form of free acid. PGE1 was the major prostaglandin detected in DGLA-supplemented culture supernatants, whose production prevailed over ARA-derived PGE2 and PGD2, which were less affected by LPS-stimulation compared with the vehicle control. An overall pattern of change indicated DGLA’s induced alleviation of the inflammatory state. Finally, our results indicate that microalgae-derived, DGLA-enriched ethyl esters (30%) exhibited similar activities to DGLA ethyl esters, strengthening the potential of this microalga as a potent source of this rare anti-inflammatory fatty acid.

scholarly journals Local and systemic influence of toxic levels of airborne ozone on the inflammatory response in rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Małgorzata Chmielewska-Krzesińska ◽  
Krzysztof Wąsowicz
Keyword(s):  
Inflammatory Response ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Interleukin 10 ◽  
Necrosis Factor Alpha ◽  
Genes Expression ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Abstract Introduction Ozone is not harmful itself; however, it directly oxidises biomolecules and produces radical-dependent cytotoxicity. Exposure to ozone is by inhalation and therefore the lungs develop the main anti-inflammatory response, while ozone has an indirect impact on the other organs. This study investigated the local and systemic effects of the ozone-associated inflammatory response. Material and Methods Three groups each of 5 Wistar Han rats aged 6 months were exposed for 2h to airborne ozone at 0.5 ppm and a fourth identical group were unexposed controls. Sacrifice was at 3h after exposure for control rats and one experimental group and at 24 h and 48 h for the others. Lung and liver samples were evaluated for changes in expression of transforming growth factor beta 1, anti-inflammatory interleukin 10, pro-inflammatory tumour necrosis factor alpha and interleukin 1 beta and two nuclear factor kappa-light-chain-enhancer of B cells subunit genes. Total RNA was isolated from the samples in spin columns and cDNA was synthesised in an RT-PCR. Expression levels were compared to those of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and analysed statistically. Results All variables changed non-linearly over time comparing experimental groups to the control. Conspicuous expression changes in the subunit genes and cytokines were observed in both evaluated organs. Conclusion Locally and systemically, inflammation responses to ozone inhalation include regulation of certain genes’ expression. The mechanisms are unalike in lungs and liver but ozone exerts a similar effect in both organs. A broader range of variables influential on ozone response should be studied in the future.

Comparing the effect of intestinal bacteria from rabbit, pig, and chicken on inflammatory response in cultured rabbit crypt and villus

2019 ◽  
Vol 65 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Hong Xiao Cui ◽  
Xiu Rong Xu
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Intestinal Bacteria ◽  
Inflammatory Factors ◽  
Rabbit Ileum ◽  
Necrosis Factor Alpha ◽  
Heat Treated ◽  
Tnf Α ◽  
Factor Alpha ◽  
Anti Inflammatory

Rabbit is susceptible to intestinal infection, which often results in severe inflammatory response. To investigate whether the special community structure of rabbit intestinal bacteria contributes to this susceptibility, we compared the inflammatory responses of isolated rabbit crypt and villus to heat-treated total bacteria in pig, chicken, and rabbit ileal contents. The dominant phylum in pig and chicken ileum was Firmicutes, while Bacteroidetes was dominant in rabbit ileum. The intestinal bacteria from rabbit induced higher expression of toll-like receptor 4 (TLR4) in rabbit crypt and villus (P < 0.05). TLR2 and TLR3 expression was obviously stimulated by chicken and pig intestinal bacteria (P < 0.05) but not by those of rabbit. The ileal bacteria from those three animals all increased the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in crypts and villus (P < 0.05). Chicken and pig ileal bacteria also stimulated the expression of anti-inflammatory factors interferon beta (IFN-β) and IL-10 (P < 0.05), while those of rabbit did not (P > 0.05). In conclusion, a higher abundance of Gram-negative bacteria in rabbit ileum did not lead to more expressive pro-inflammatory cytokines in isolated rabbit crypt and villus, but a higher percentage of Lactobacillus in chicken ileum might result in more expressive anti-inflammatory factors.

scholarly journals PGD Synthase and PGD2in Immune Resposne

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Myungsoo Joo ◽  
Ruxana T. Sadikot
Keyword(s):  
Arachidonic Acid ◽  
Inflammatory Response ◽  
Inflammatory Diseases ◽  
Disease Process ◽  
Therapeutic Approaches ◽  
Enzyme Reactions ◽  
Common Precursor ◽  
Anti Inflammatory ◽  
Novel Therapeutic

PGD2is formed from arachidonic acid by successive enzyme reactions: oxygenation of arachidonic acid to PGH2, a common precursor of various prostanoids, catalyzed by cyclooxygenase, and isomerization of PGH2to PGD2by PGD synthases (PGDSs). PGD2can be either pro- or anti-inflammatory depending on disease process and etiology. The anti-inflammatory and immunomodulatory attributes of PGDS/PGD2provide opportunities for development of novel therapeutic approaches for resistant infections and refractory inflammatory diseases. This paper highlights the role of PGD synthases and PGD2 in immune inflammatory response.

scholarly journals Angiogenin Reduces Immune Inflammation via Inhibition of TANK-Binding Kinase 1 Expression in Human Corneal Fibroblast Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Seung Hoon Lee ◽  
Kyoung Woo Kim ◽  
Kyong-Mi Min ◽  
Kyu-Wan Kim ◽  
Soo-Ik Chang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mrna Expression ◽  
Nuclear Translocation ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Necrosis Factor Alpha ◽  
Protein Levels ◽  
Immune Mediated ◽  
Chemotactic Protein ◽  
Anti Inflammatory

Angiogenin (ANG) is reportedly multifunctional, with roles in angiogenesis and autoimmune diseases. This protein is involved in the innate immune system and has been implicated in several inflammatory diseases. Although ANG may be involved in the anti-inflammatory response, there is no evidence that it has direct anti-inflammatory effects. In this study we sought to determine whether ANG has an anti-inflammatory effect in human corneal fibroblasts (HCFs) exposed to media containing tumor necrosis factor-alpha (TNF-α). We found that ANG reduced the mRNA expression of interleukin-1 beta (IL-1β), -6, -8 and TNF-αreceptors (TNFR) 1 and 2. In contrast, ANG increased the mRNA expression of IL-4 and -10. Protein levels of TANK-binding kinase 1 (TBK1) were reduced by ANG in HCFs treated with TNF-α. Moreover, ANG diminished the expression of IL-6 and -8 and monocyte chemotactic protein- (MCP-) 1. The protein expression of nuclear factor-κB (NF-κB) was downregulated by ANG treatment. These findings suggest that ANG suppressed the TNF-α-induced inflammatory response in HCFs through inhibition of TBK1-mediated NF-κB nuclear translocation. These novel results are likely to play a significant role in the selection of immune-mediated inflammatory therapeutic targets and may shed light on the pathogenesis of immune-mediated inflammatory diseases.

scholarly journals Beneficial Dysregulation of the Time Course of Inflammatory Mediators in Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Factor-Deficient Mice

2010 ◽  
Vol 17 (5) ◽  
pp. 699-704 ◽  
Author(s):  
Sreedevi Srinivasan ◽  
Susan E. Leeman ◽  
Salomon Amar
Keyword(s):  
Tumor Necrosis Factor ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Tumor Necrosis ◽  
Time Course ◽  
Lethal Dose ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

ABSTRACT To begin to understand the surprising survival of macrophage-specific lipopolysaccharide-induced tumor necrosis factor alpha factor-deficient (macLITAF−/−) animals after a lethal dose of lipopolysaccharide (LPS), as reported earlier, the present follow-up study focuses on the role of LITAF in the regulation of inflammatory cytokines secreted in response to lethal or sublethal doses of LPS administered to wild-type (WT) and macLITAF−/− mice. A time course study of kinase expression in peritoneal macrophages revealed increased phosphorylation of prosurvival kinases Akt, Erk1/2, and ribosomal S6 kinase (RSK) in macLITAF−/− mice compared to that in WT mice (n = 8), confirming their role in LPS-mediated diseases. macLITAF−/− mice (n = 8) survived a lethal dose of LPS plus d-galactosamine (d-GalN), expressing lower serum levels of pro- and anti-inflammatory cytokines than the WT levels. To extend our knowledge on LPS-induced inflammatory events, an effective sublethal dose of LPS was administered to the animals (n = 14). WT animals exhibited an acute inflammatory response that decreased after 4 h. Interestingly, macLITAF−/− mice exhibited an initial delay in the secretion of proinflammatory cytokines that peaked after 8 h and reached WT levels after 18 h. Anti-inflammatory cytokine secretions were initially delayed but increased after 4 h and remained elevated compared to WT levels, even after 18 h. Our results demonstrate that LITAF deficiency in vivo affects cytokines other than TNF-α and influences the balance between the pro- and anti-inflammatory cytokines, which protects the animals from the deleterious effects of an LPS-induced inflammatory response, resulting in a beneficial host regulation of inflammatory cytokines and in enhanced survival. Therapeutic intervention aimed at reducing LITAF via kinase modulators may prove useful in preventing LPS-induced mortality.

210 Horse allogeneic mesenchymal stem cells perform homing and ameliorate endometrial inflammation after induced endometritis of mares

2020 ◽  
Vol 32 (2) ◽  
pp. 233
Author(s):  
F. Navarrete ◽  
F. Saravia ◽  
G. Cisterna ◽  
F. Rojas ◽  
L. Rodríguez-Alvarez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Response ◽  
Inflammatory Markers ◽  
Polymorphonuclear Leucocytes ◽  
Necrosis Factor Alpha ◽  
Sterile Saline ◽  
Markers Of Inflammation ◽  
Anti Inflammatory ◽  
Uterine Body

Post-mating induced endometritis (PMIE) is an acute inflammatory response of the endometrium to spermatozoa, linked to an incapability of some mares to drain out the fluids associated with inflammation. This is of pivotal importance for reproductive success in mares. Mesenchymal stem cells (MSCs) are potential candidates for anti-inflammatory uterine therapies. Here, we aimed to study inflammatory markers in the endometrium of healthy mares and of those with induced endometritis, before and after intrauterine inoculation of MSCs, and to characterise their homing potential invivo in an induced endometritis horse model. Nine mares during their ovulatory season were selected after gynaecologic examination (absence of free liquid in the uterus, no polymorphonuclear leucocytes (PMNs) at cytology, negative bacteriology, and grade I in Kenney's scale on uterine biopsies). Mares were infused in the uterine body with 2mL of 500×106 spermmL−1 previously killed by repeated frozen-thawing cycles. At 3h, uteri were flushed with 250mL of sterile saline and the inflammatory response was monitored in the lavages and biopsies. Parameters measured included cytology, protein expression of inflammatory markers (supernatant) after lavage centrifugation (800×g, 10min), ELISA, and immunostaining for interleukin (IL)-6 and tumor necrosis factor alpha (TNFα). The mares were divided into three groups (3 mares each). Then, 24h after dead sperm challenge, group 1 received intrauterine infusion of 2×107 adipose MSC in 0.9% sterile saline; group 2, received the same amount of endometrial MSCs in the same vehicle; and group 3 received only saline. The volume of infusion in the uterine body was 20mL for all groups. Cells (passage 4) were previously labelled with 10μM Vybrant CFDA SE Cell Tracer Kit (ThermoFisher Scientific). After 48h, the same lavages, biopsies, and measurements as described above were performed. Additional biopsies were taken at Days 10 and 30 after intrauterine infusions. Biopsies were split in two, one for confocal microscopy and the other for quantitative PCR. Endometritis was induced in all mares, as judged by cytology and expression of protein markers of inflammation. After 48h, reduction in IL-6 and TNFα was detected by immunostaining of biopsies and confirmed by ELISA in the lavages, as well as by PCR. Homing was detected in all mares infused with MSC and it persisted at Days 10 and 30 after infusion. No homing was found in the control mares. As a result of these experiments, we conclude that inoculation of MSCs significantly reduced inflammation independently of the origin of the cells (adipose or endometrial). Both types of cells were nested in the endometrium at low quantities, although the number of cells actually detected at fixed time points was not quantified. Overall, we can propose that, given the number of homed cells detected and the marked decrease in inflammatory markers after inoculation of cells, MSCs exert their anti-inflammatory function preferentially by a paracrine mechanism and not necessarily by nesting and proliferation, although both events occur. Funding for this study was provided by Fondecyt 1150757.

A Polyphenolic Complex Attenuates Inflammatory Response and Blood- Brain Barrier Disruption

2020 ◽  
Vol 17 (3) ◽  
pp. 286-293 ◽  
Author(s):  
Yuting Bian ◽  
Toru Yamashita ◽  
Yuki Taira ◽  
Jingwei Shang ◽  
Keiichiro Tsunoda ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Blood Brain Barrier ◽  
Rosmarinic Acid ◽  
Infarct Volume ◽  
Brain Barrier ◽  
Total Phenolic ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Blood Brain ◽  
Anti Inflammatory

Background: Cerebral ischemia causes a strong inflammatory response. Neumentix is a dietary supplement containing 14.9% rosmarinic acid and 29.9% total phenolic content, which has been proved to be beneficial against inflammatory response. Therefore, Neumentix’s effect on anti-inflammatory and blood brain barrier (BBB) disruption in transient middle cerebral artery occlusion (tMCAO) model mice is investigated in this study. Methods: After the pretreatment of vehicle or Neumentix 134 mg/kg/d, intraperitoneal injection (i.p.) (containing rosmarinic acid 20 mg/kg/d) for 14 days, mice were subjected to tMCAO for 60 min and kept receiving vehicle or Neumentix daily 5 days afterward. Results: Neumentix treatment ameliorated neurobehavioral impairment in the corner test (5d after tMCAO, **P<0.01), reduced infarct volume (#P<0.05), suppressed expression of ionized calciumbinding adapter molecule-1 (Iba-1), tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) (###P<0.001), and improved the integrity of BBB (§P<0.05) at 5 days after tMCAO. Conclusios: The present study provided an evidence of Neumentix’s anti-inflammatory and neuroprotection effect against BBB disruption on experimental tMCAO model mice, suggesting that Neumentix could be a potential therapeutic agent for stroke.

scholarly journals Comparative Anti-inflammatory Effects of Anti-arthritic Herbal Medicines and Ibuprofen

2014 ◽  
Vol 9 (9) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Joshua J. Kang ◽  
Mohammed A. Samad ◽  
Kye S. Kim ◽  
Soochan Bae
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Herbal Medicines ◽  
C2c12 Cells ◽  
Necrosis Factor Alpha ◽  
Drug Concentrations ◽  
Toxic Concentration ◽  
Chemotactic Protein ◽  
Anti Inflammatory ◽  
Toxic Concentrations

Non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen, are widely used over-the-counter drugs to treat arthritis, but they are often associated with side effects. Herbal medicines have been used to treat various diseases such as arthritis, but the scientific profiles are not well understood. In this study, we examined, in comparison with ibuprofen, the inhibitory effects on various inflammatory markers of the most commonly used herbal medicines to treat arthritis, boswellia (Boswellia sapindales), licorice (Glycyrrhiza glabra), guggul (Commiphora wightii), and neem (Azadirachta indica). To elicit inflammatory response, we exposed mouse myoblast C2C12 cells to lipopolysaccharide (LPS). Tumor necrosis factor-alpha (TNF-α) and monocyte chemotactic protein-1 (MCP-1), which are cytokines activated during an inflammatory response, were determined. The optimal non-toxic concentration was determined by exposing different concentrations of drugs (from 0.01 to 10 mg/mL). Cell death measurement revealed that the drug concentrations lower than 0.05 mg/mL were non-toxic concentrations for each drug, and these doses were used for the main experiments. We found that neem and licorice showed robust anti-inflammatory responses compared with ibuprofen. However, boswellia and guggul did not demonstrate significant anti-inflammatory responses. We concluded that neem and licorice are more effective than ibuprofen in suppressing LPS-induced inflammation in C2C12 cells.

scholarly journals Synthesis, Physicochemical Characteristics and Plausible Mechanism of Action of an Immunosuppressive Isoxazolo[5,4-e]-1,2,4-Triazepine Derivative (RM33)

2021 ◽  
Vol 14 (5) ◽  
pp. 468
Author(s):  
Marcin Mączyński ◽  
Andrzej Regiec ◽  
Aleksandra Sochacka-Ćwikła ◽  
Iwona Kochanowska ◽  
Maja Kocięba ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Cell Activation ◽  
Chemical Shifts ◽  
Biological Activities ◽  
Physicochemical Characteristics ◽  
Splenocyte Proliferation ◽  
Necrosis Factor Alpha ◽  
Enhanced Production ◽  
Anti Inflammatory

Previous studies demonstrated strong anti-inflammatory properties of isoxazolo[5,4-e]-1,2,4-triazepine (RM33) in vivo. The aim of this investigation was to describe synthesis, determine physicochemical characteristics, evaluate biological activities in murine and human in vitro models, as well as to propose mechanism of action of the compound. The compound was devoid of cell toxicity up to 100 μg/mL against a reference A549 cell line. Likewise, RM33 did not induce apoptosis in these cells. The compound stimulated concanavalin A (ConA)-induced splenocyte proliferation but did not change the secondary humoral immune response in vitro to sheep erythrocytes. Nevertheless, a low suppressive effect was registered on lipopolysaccharide (LPS)-induced splenocyte proliferation and a stronger one on tumor necrosis factor alpha (TNFα) production by rat peritoneal cells. The analysis of signaling pathways elicited by RM33 in nonstimulated resident cells and cell lines revealed changes associated with cell activation. Most importantly, we demonstrated that RM33 enhanced production of cyclooxygenase 2 in LPS-stimulated splenocytes. Based on the previous and herein presented results, we conclude that RM33 is an efficient, nontoxic immune suppressor with prevailing anti-inflammatory action. Additionally, structural studies were carried out with the use of appropriate spectral techniques in order to unequivocally confirm the structure of the RM33 molecule. Unambiguous assignment of NMR chemical shifts of carbon atoms of RM33 was conducted thanks to full detailed analysis of 1H, 13C NMR spectra and their two-dimensional (2D) variants. Comparison between theoretically predicted chemical shifts and experimental ones was also carried out. Additionally, N-deuterated isotopologue of RM33 was synthesized to eliminate potentially disturbing frequencies (such as NH, NH2 deformation vibrations) in the carbonyl region of the IR (infrared) spectrum to confirm the presence of the carbonyl group.

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