scholarly journals Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue

2014 ◽  
Vol 307 (1) ◽  
pp. C39-C54 ◽  
Author(s):  
Romain A. Colas ◽  
Masakazu Shinohara ◽  
Jesmond Dalli ◽  
Nan Chiang ◽  
Charles N. Serhan

Resolution of acute inflammation is an active process locally controlled by a novel genus of specialized pro-resolving mediators (SPM) that orchestrate key resolution responses. Hence, it is of general interest to identify individual bioactive mediators and profile their biosynthetic pathways with related isomers as well as their relation(s) to classic eicosanoids in mammalian tissues. Lipid mediator (LM)-SPM levels and signature profiles of their biosynthetic pathways were investigated using liquid chromatography-tandem mass spectrometry (LC-MS-MS)-based LM metabololipidomics. LM and SPM were identified using ≥6 diagnostic ions and chromatographic behavior matching with both authentic and synthetic materials. This approach was validated using the composite reference plasma (SRM1950) of 100 healthy individuals. Using targeted LM metabololipidomics, we profiled LM and SPM pathways in human peripheral blood (plasma and serum) and lymphoid organs. In these, we identified endogenous SPM metabolomes, namely, the potent lipoxins (LX), resolvins (Rv), protectins (PD), and maresins (MaR). These included RvD1, RvD2, RvD3, MaR1, and NPD1/PD1, which were identified in amounts within their bioactive ranges. In plasma and serum, principal component analysis (PCA) identified signature profiles of eicosanoids and SPM clusters. Plasma-SPM increased with omega-3 and acetylsalicylic acid intake that correlated with increased phagocytosis of Escherichia coli in whole blood. These findings demonstrate an approach for identification of SPM pathways (e.g., resolvins, protectins, and maresins) in human blood and lymphoid tissues that were in amounts commensurate with their pro-resolving, organ protective, and tissue regeneration functions. LM metabololipidomics coupled with calibration tissues and physiological changes documented herein provide a tool for functional phenotypic profiling.

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2260
Author(s):  
Juliana C. Reis-Canaan ◽  
Marcelo M. Canaan ◽  
Patrícia D. Costa ◽  
Tamires P. Rodrigues-Juliatte ◽  
Michel C. A. Pereira ◽  
...  

Chronotype (CT) has been associated with predisposition to chronic noncommunicable diseases (CNCDs), such as diabetes mellitus and obesity. However, the effects of CT on individuals assisted by public health systems (PHSs) in middle-up economies are still poorly explored. The objective of this study was to evaluate the relationship between CT and clinical, sociobehavioral and nutritional aspects in adults assisted by a PHS in Brazil. This is a population-based cross-sectional study. The sample consisted of 380 individuals, selected through probabilistic sampling by clusters, in all health units in a city of approximately 100 thousand inhabitants. Data collection was performed during home visits, by means of general and nutritional interviews, anthropometric measurements and the Morningness–Eveningness Questionnaire (MEQ). Statistical analysis comprised chi-square test and principal component analysis (CPA) followed by Fisher’s discriminant analysis to determine aspects associated with each CT (morning, evening or intermediate). With the aim of explaining the variation in the CT scores, the consumption of micronutrients (corrected to the total energy intake) and other individual and sociodemographic variables were used as explanatory factors in the adjustment of a linear regression model. The morning group was characterized by older men, with less than eight years of schooling, with low body mass index (BMI) and with low intake of omega-6, omega-3, sodium, zinc, thiamine, pyridoxine and niacin. The evening group, on the other hand, was composed of younger individuals, with a high consumption of these same nutrients, with high BMI and a higher frequency of heart diseases (p < 0.05). It was concluded that most morning CT individuals were elderly thin males with lower consumption of omega-6 and -3, sodium, zinc, thiamine, pyridoxine and niacin, whereas evening individuals were younger, had higher BMI and had higher consumption of the studied micronutrients. The identification of circadian and behavioral risk groups can help to provide preventive and multidisciplinary health promotion measures.


Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 216-225 ◽  
Author(s):  
Anthony D. Cristillo ◽  
Mirtha J. Macri ◽  
Barbara E. Bierer

Abstract The chemokine superfamily consists of small (8-10 kDa) molecules that function to attract, selectively, different subsets of leukocytes. Binding of chemokines to their appropriate G-protein–coupled receptors is necessary for primary immune responses and for homing of leukocytes to lymphoid tissues. Here, we have characterized the signaling pathways in primary T lymphocytes that regulate chemokine gene induction using an RNase protection assay. Dependence on stimulation through the coreceptor CD28 and sensitivity to the calcineurin inhibitors cyclosporine and tacrolimus were studied using purified human peripheral blood lymphocytes. Lymphotactin (Ltn), macrophage inflammatory protein (MIP)–1α, and MIP-1β were all rapidly induced and sensitive to cyclosporine treatment. At later time points, the expression of MIP-1α and MIP-1β, but not of Ltn, was restored despite the inhibition of calcineurin activity. By contrast, the induction of interleukin-8 was delayed and was found to be cyclosporine insensitive. Calcineurin activity of IP-10 mRNA induction was contingent on the specific T-cell stimulation conditions, suggesting that IP-10 expression is modulated by calcineurin-dependent and -independent signaling pathways. Differential chemokine expression profiles result from the engagement of T-cell coreceptors and the requirement for, and the dependence on, calcineurin phosphatase activity.


Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3315 ◽  
Author(s):  
Ling Luo ◽  
Weili Han ◽  
Jinyan Du ◽  
Xia Yang ◽  
Mubing Duan ◽  
...  

Influenza A virus (IAV) infection is still a major global threat for humans, especially for the risk groups: young children and the elderly. The currently licensed antiviral drugs target viral factors and are prone to viral resistance. In recent years, a few endogenous small molecules from host, such as estradiol and omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protection D1 (PD1), were demonstrated to be capable of inhibiting IAV infection. Chenodeoxycholic acid (CDCA), one of the main primary bile acids, is synthesized from cholesterol in the liver and classically functions in emulsification and absorption of dietary fats. Clinically, CDCA has been used in the treatment of patients with cholesterol gallstones for more than five decades. In this study, we showed that CDCA attenuated the replication of three subtypes of influenza A virus, including a highly pathogenic H5N1 strain, in A549 and MDCK cell cultures with IC50 ranging from 5.5 to 11.5 μM. Mechanistically, CDCA effectively restrained the nuclear export of viral ribonucleoprotein (vRNP) complexes. In conclusion, as an endogenous physiological small molecule, CDCA can inhibit IAV replication in vitro, at least in part, by blocking vRNP nuclear export, and affords further studies for development as a potential antiviral agent against IAV infections.


2019 ◽  
Vol 41 (6) ◽  
pp. 757-766 ◽  
Author(s):  
Miguel Carracedo ◽  
Gonzalo Artiach ◽  
Hildur Arnardottir ◽  
Magnus Bäck

Abstract Omega-3 fatty acids serve as the substrate for the formation of a group of lipid mediators that mediate the resolution of inflammation. The cardiovascular inflammatory response in atherosclerosis and vascular injury is characterized by a failure in the resolution of inflammation, resulting in a chronic inflammatory response. The proresolving lipid mediator resolvin E1 (RvE1) is formed by enzymatic conversion of the omega-3 fatty acid eicosapentaenoic acid (EPA), and signals resolution of inflammation through its receptor ChemR23. Importantly, the resolution of cardiovascular inflammation is an active, multifactorial process that involves modulation of the immune response, direct actions on the vascular wall, as well as close interactions between macrophages and vascular smooth muscle cells. Promoting anti-atherogenic signalling through the stimulation of endogenous resolution of inflammation pathways may provide a novel therapeutic strategy in cardiovascular prevention.


2013 ◽  
Vol 153 (4) ◽  
pp. 355-360 ◽  
Author(s):  
Y. Isobe ◽  
M. Arita ◽  
R. Iwamoto ◽  
D. Urabe ◽  
H. Todoroki ◽  
...  

2013 ◽  
Vol 67 (3) ◽  
Author(s):  
Adriána Bednárová ◽  
Ján Mocák ◽  
Walter Gössler ◽  
Margit Velik ◽  
Josef Kaufmann ◽  
...  

AbstractThe main aim of the present study was to find differences in the content of fatty acids and variations in elemental composition in beef samples of longissimus dorsi muscle related to cattle age and gender. A further goal was to describe interrelations among the selected variables (descriptors) characterising the samples. For this purpose, an extensive data table was compiled, which contains chemical descriptors specifying forty-six beef samples originating from four well-known Austrian grassland-based beef labels. The following descriptors were investigated: (a) concentrations of 33 fatty acids, (b) concentrations of 19 elements, (c) contents of dry-mass, protein, intramuscular fat, and ash, (d) total content of saturated fatty acids (SFA), mono-unsaturated fatty acids (MUFA), and poly-unsaturated fatty acids (PUFA), (e) total contents of omega-3 (n-3) and omega-6 (n-6) PUFA and their ratio. The correlation analysis provided a number of statistically significant correlations among the descriptors, which were concordant with the results of the principal component analysis and cluster analysis. Furthermore, the effect of age and gender of cattle (both acting as target factors) on the fatty acid content and elemental composition of beef was examined by analysis of variance (ANOVA) and appropriate non-parametric tests. Several important interrelations among the beef characteristics investigated were also discovered. Finally, the most relevant beef descriptors were utilised in linear discrimination analysis (LDA) for predicting the slaughter age of the cattle for beef authentication.


2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
E. Patterson ◽  
R. Wall ◽  
G. F. Fitzgerald ◽  
R. P. Ross ◽  
C. Stanton

Omega-6 (n-6) polyunsaturated fatty acids (PUFA) (e.g., arachidonic acid (AA)) and omega-3 (n-3) PUFA (e.g., eicosapentaenoic acid (EPA)) are precursors to potent lipid mediator signalling molecules, termed “eicosanoids,” which have important roles in the regulation of inflammation. In general, eicosanoids derived from n-6 PUFA are proinflammatory while eicosanoids derived from n-3 PUFA are anti-inflammatory. Dietary changes over the past few decades in the intake of n-6 and n-3 PUFA show striking increases in the (n-6) to (n-3) ratio (~15 : 1), which are associated with greater metabolism of the n-6 PUFA compared with n-3 PUFA. Coinciding with this increase in the ratio of (n-6) : (n-3) PUFA are increases in chronic inflammatory diseases such as nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, obesity, inflammatory bowel disease (IBD), rheumatoid arthritis, and Alzheimer's disease (AD). By increasing the ratio of (n-3) : (n-6) PUFA in the Western diet, reductions may be achieved in the incidence of these chronic inflammatory diseases.


2015 ◽  
Vol 39 (4) ◽  
pp. 372-380 ◽  
Author(s):  
Gisele Teixeira de Souza Sora ◽  
Aloisio Henrique Pereira Souza ◽  
Acácio Antônio Ferreira Zielinski ◽  
Charles Windson Isidoro Haminiuk ◽  
Makoto Matsushita ◽  
...  

Fatty acids have a great metabolic and structural importance. Evaluation of fatty acid composition of peppers is still incomplete. Pulps and seeds from six varieties of the genus Capsicum were evaluated in this work with respect to their contents in fatty acids. A total of 25 different fatty acids, including some with odd number of carbons were identified in the samples. The most abundant fatty acids were palmitic (16:0), oleic (18:1n-9) and linoleic (18:2n-6) acids. The polyunsaturated:saturated fatty acid (PUFA/SFA) ratios for all peppers were high due to the elevated amounts of polyunsaturated acids, particularly linoleic acid. In the pulps, the omega-6/omega-3 ratios ranging from 1.28 to 4.33, were relatively adequate if one considers that ratios between 0.25 and 1.0 in the human diet are regarded as highly appropriate. In the seeds, the levels of omega-3 were very low whereas the levels of omega-6 were high, leading to very inadequate omega-6/omega-3 ratios ranging from 74.2 to 279.6. Principal component analysis (PCA) explained 93.49% of the total variance of the data. Considering the PUFA/SFA ratio and omega-6/omega-3 ratio, our data suggest that, among the peppers of the genus Capsicum evaluated in this work, the bell pepper and orange habanero pepper present the best nutritional characteristics concerning fatty acid composition.


Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2868 ◽  
Author(s):  
Kento Sawane ◽  
Takahiro Nagatake ◽  
Koji Hosomi ◽  
So-ichiro Hirata ◽  
Jun Adachi ◽  
...  

The metabolism and generation of bioactive lipid mediators are key events in the exertion of the beneficial effects of dietary omega-3 fatty acids in the regulation of allergic inflammation. Here, we found that dietary linseed oil, which contains high amounts of alpha-linolenic acid (ALA) dampened allergic rhinitis through eosinophilic production of 15-hydroxyeicosapentaenoic acid (15-HEPE), a metabolite of eicosapentaenoic acid (EPA). Lipidomic analysis revealed that 15-HEPE was particularly accumulated in the nasal passage of linseed oil-fed mice after the development of allergic rhinitis with the increasing number of eosinophils. Indeed, the conversion of EPA to 15-HEPE was mediated by the 15-lipoxygenase activity of eosinophils. Intranasal injection of 15-HEPE dampened allergic symptoms by inhibiting mast cell degranulation, which was mediated by the action of peroxisome proliferator-activated receptor gamma. These findings identify 15-HEPE as a novel EPA-derived, and eosinophil-dependent anti-allergic metabolite, and provide a preventive and therapeutic strategy against allergic rhinitis.


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