Geobarrettin D, a Rare Herbipoline-Containing 6-Bromoindole Alkaloid from .

Geobarrettin D (), a new bromoindole alkaloid, was isolated from the marine sponge collected from Icelandic waters. Its structure was elucidated by 1D, and 2D NMR (including H-N HSQC, H-N HMBC spectra), as well as HRESIMS data. Geobarrettin D () is a new 6-bromoindole featuring an unusual purinium herbipoline moiety.

Keratinocytes secrete multiple inflammatory and immune biomarkers, which are regulated by LL-37, in a psoriasis mimicking microenvironment.

Psoriasis is an autoimmune disease driven by a Th17 response linked to the antimicrobial peptide (AMP) LL-37 that has been connected to the induction and chronicity of psoriasis. We show that keratinocytes secrete various immune biomarkers with a direct link to psoriasis immunopathogenesis. Under pro-inflammatory microenvironmental conditions, LL-37 was found to regulate keratinocyte secretion of various immune biomarkers (eg C-X-C motif chemokine ligand (CXCL)8 and interleukin (IL)-1β) and alter extracellular signal-regulated kinase (ERK)1/2 signalling.

Dietary Fish Oil Increases the Number of CD11bCD27 NK Cells at the Inflammatory Site and Enhances Key Hallmarks of Resolution of Murine Antigen-Induced Peritonitis.

Purpose: To determine the effects of dietary omega-3 polyunsaturated fatty acids (PUFAs) on recruitment of natural killer (NK) cells and resolution responses in antigen-induced peritonitis in mice.

Methods: Mice were fed fish oil-enriched or control diets, immunized twice and challenged intraperitoneally with methylated bovine serum albumin. Prior to and at different time-points following inflammation induction, expression of surface molecules on peritoneal cells was determined by flow cytometry, concentration of soluble mediators in peritoneal fluid by ELISA or Luminex, and of lipid mediators by LC-MS/MS, and number of apoptotic cells in mesenteric lymph nodes by TUNEL staining.

Docosahexaenoic Acid Modulates NK Cell Effects on Neutrophils and Their Crosstalk.

Natural killer (NK) cells and neutrophils engage in crosstalk that is important in inflammation and likely also for resolution of inflammation. NK cells activate neutrophils and induce their infiltration to the inflamed sites but may also influence their apoptosis and their subsequent efferocytosis by macrophages. Several studies indicate that docosahexaenoic acid (DHA) can inhibit NK cell cytotoxicity but the effects of DHA on the ability of NK cells to engage in crosstalk with neutrophils and affect their functions have not been described.

Bromotryptamine and Imidazole Alkaloids with Anti-inflammatory Activity from the Bryozoan .

Chemical investigation of the marine bryozoan collected in Iceland resulted in isolation of 13 new bromotryptamine alkaloids, flustramines Q-W (-) and flustraminols C-H (-), and two new imidazole alkaloids, flustrimidazoles A and B ( and ), together with 12 previously described compounds (-). Their structures were established by detailed spectroscopic analysis using 1D and 2D NMR and HRESIMS. Structure was verified by calculations of the C and H NMR chemical shifts using density functional theory.

Anti-Inflammatory and Proresolving Effects of the Omega-6 Polyunsaturated Fatty Acid Adrenic Acid.

Polyunsaturated fatty acids (PUFAs) and their metabolites are potent regulators of inflammation. Generally, omega ()-3 PUFAs are considered proresolving whereas -6 PUFAs are classified as proinflammatory. In this study, we characterized the inflammatory response in murine peritonitis and unexpectedly found the accumulation of adrenic acid (AdA), a poorly studied -6 PUFA.

Exopolysaccharides from Cyanobacterium aponinum induce a regulatory dendritic cell phenotype and inhibit SYK and CLEC7A expression in dendritic cells, T cells and keratinocytes.

Regular bathing in the Blue Lagoon has beneficial effects on psoriasis. Previously, we showed that exopolysaccharides (EPS-Ca) secreted by Cyanobacterium aponinum, a dominating organism in the Blue Lagoon, increased IL-10 secretion by human dendritic cells (DCs). In addition, co-culturing allogeneic CD4 T cells with DCs matured in the presence of EPS-Ca increased differentiation of T cells into T regulatory cells at the cost of the disease inducing Th17 cells.

Impact of dibenzocyclooctadiene lignans from Schisandra chinensis on the redox status and activation of human innate immune system cells.

Redox signaling has been established as an essential component of inflammatory responses, and redox active compounds are of interest as potential immunomodulatory agents. Dibenzocyclooctadiene lignans isolated from Schisandra chinensis, a medicinal plant with widespread use in oriental medicine, have been implicated to possess immunomodulatory properties but their effects on the human innate immune system cells have not been described. In this contribution, data are presented on the impact of schisandrin, schisandrin B and schisandrin C on human monocytic cell redox status, as well as their impact on dendritic cell maturation and T cell activation capacity and cytokine production.

6-Bromoindole Derivatives from the Icelandic Marine Sponge : Isolation and Anti-Inflammatory Activity.

An UPLC-qTOF-MS-based dereplication study led to the targeted isolation of seven bromoindole alkaloids from the sub-Arctic sponge . This includes three new metabolites, namely geobarrettin A⁻C (⁻) and four known compounds, barettin (), 8,9-dihydrobarettin (), 6-bromoconicamin (), and l-6-bromohypaphorine () The chemical structures of compounds ⁻ were elucidated by extensive analysis of the NMR and HRESIMS data. The absolute stereochemistry of geobarrettin A () was assigned by ECD analysis and Marfey's method employing the new reagent l--(1-fluoro-2,4-dinitrophenyl)tryptophanamide (l-FDTA).

Natural killer cells play an essential role in resolution of antigen-induced inflammation in mice.

This study examined whether NK cells are important for resolution of antigen-induced inflammation. C57BL/6 mice were immunized twice with methylated BSA (mBSA) and inflammation induced by intraperitoneal injection of mBSA. Mice were injected intravenously with anti-asialo GM1 (αASGM1) or a control antibody 24h prior to peritonitis induction and peritoneal exudate collected at different time points.

Lipophilic fractions from the marine sponge Halichondria sitiens decrease secretion of pro-inflammatory cytokines by dendritic cells and decrease their ability to induce a Th1 type response by allogeneic CD4 T cells.

Context: Halichondria (Halichondriidae) marine sponges contain components possessing various biological activities, but immunomodulation is not among the ones reported.

Objective: This study evaluated the immunomodulatory effects of fractions/compounds from Halichondria sitiens Schmidt.

Materials And Methods: Crude dichloromethane/methanol extracts of H.

Immunomodulatory N-acyl Dopamine Glycosides from the Icelandic Marine Sponge Myxilla incrustans Collected at a Hydrothermal Vent Site.

A chemical investigation of the sponge (Porifera) Myxilla incrustans collected from the unique submarine hydrothermal vent site Strytan, North of Iceland, revealed a novel family of closely related N-acyl dopamine glycosides. Three new compounds, myxillin A (1), B (2) and C (3), were isolated and structurally elucidated using several analytical techniques, such as HR-MS, 1D and 2D NMR spectroscopy. Myxillin A (1) and B (2)were shown to be structurally similar, composed of a dopamine moiety, but differ in the acyl chain length and saturation.

A polysaccharide fraction from Achillea millefolium increases cytokine secretion and reduces activation of Akt, ERK and NF-κB in THP-1 monocytes.

Achillea millefolium has been used in traditional medicine for a number of ailments, including skin inflammation and wounds. A polysaccharide fraction (Am-25-d) isolated from aqueous extract from A. millefolium had an average molecular weight of 270 kDa and a monosaccharide composition of GalA, Gal, Ara, Xyl, Rha in molar ratio of 28:26:23:9:7.

Acute phase inflammation is characterized by rapid changes in plasma/peritoneal fluid N-glycosylation in mice.

Murine zymosan-induced peritonitis is a widely used model for studying the molecular and cellular events responsible for the initiation, persistence and/or resolution of inflammation. Among these events, it is becoming increasingly evident that changes in glycosylation of proteins, especially in the plasma and at the site of inflammation, play an important role in the inflammatory response. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)-based glycosylation profiling, we investigated the qualitative and quantitative effect of zymosan-induced peritonitis on N-glycosylation in mouse plasma and peritoneal fluid.

Differential mobility separation of leukotrienes and protectins.

Differential mobility spectrometry (DMS) is capable of separating stereoisomeric molecular ions based on their mobility in an oscillating electrical field with an asymmetric waveform. Thus, it is an "orthogonal" technique to chromatography and (tandem) mass spectrometry. Bioactive lipids, particularly of the eicosanoid and docosanoid class feature numerous stereoisomers, which exhibit a highly specific structure-activity relationship.

Dendritic cells matured in the presence of the lycopodium alkaloid annotine direct T cell responses toward a Th2/Treg phenotype.

Annotine is a lycopodane-type alkaloid isolated from the Icelandic club moss Lycopodium annotinum ssp. alpestre. Annotine does not inhibit acetylcholinesterase, as some other lycopodium alkaloids do, and other bioactivities have not been reported.

Effect of in vitro digested cod liver oil of different quality on oxidative, proteomic and inflammatory responses in the yeast Saccharomyces cerevisiae and human monocyte-derived dendritic cells.

Background: Upon oxidation of the polyunsaturated fatty acids in fish oil, either before ingestion or, as recently shown, during the gastro-intestinal passage, a cascade of potentially cytotoxic peroxidation products, such as malondialdehyde and 4-hydroxy-2-hexenal, can form. In this study, we digested fresh and oxidised cod liver oils in vitro, monitored the levels of lipid peroxidation products and evaluated oxidative, proteomic and inflammatory responses to the two types of digests in the yeast Saccharomyces cerevisiae and human monocyte-derived dendritic cells.

Results: Digests of cod liver oil with 22-53 µmol L(-1) malondialdehyde and 0.

Exopolysaccharides from Cyanobacterium aponinum from the Blue Lagoon in Iceland increase IL-10 secretion by human dendritic cells and their ability to reduce the IL-17+RORγt+/IL-10+FoxP3+ ratio in CD4+ T cells.

Regular bathing in the Blue Lagoon in Iceland has beneficial effects on psoriasis. Cyanobacterium aponinum is a dominating member of the Blue Lagoon's microbial ecosystem. The aim of the study was to determine whether exopolysaccharides (EPSs) secreted by C.

Murine antigen-induced inflammation--a model for studying induction, resolution and the adaptive phase of inflammation.

Murine zymosan-induced peritonitis is the model most frequently used to study resolution of inflammation. However, the antigen-induced peritonitis model may be better suited for studying resolution of inflammation and the adaptive phase that follows. The objective of this study was to provide an evaluation of the kinetics of cells and mediators during induction, resolution and the adaptive immune phases of a murine antigen-induced inflammation.

A heteroglycan from the cyanobacterium Nostoc commune modulates LPS-induced inflammatory cytokine secretion by THP-1 monocytes through phosphorylation of ERK1/2 and Akt.

Cyanobacteria (blue-green algae) have been consumed as food and used in folk medicine since ancient times to alleviate a variety of diseases. Cyanobacteria of the genus Nostoc have been shown to produce complex exopolysaccharides with antioxidant and antiviral activity. Furthermore, Nostoc sp.

Dietary omega-3 fatty acids enhance the B1 but not the B2 cell immune response in mice with antigen-induced peritonitis.

The effects of omega-3 fatty acids on the adaptive immune response have mainly been analysed in vitro with varying results. How omega-3 fatty acids affect the adaptive immune response in vivo is largely unknown. This study examined the effects of dietary fish oil on the adaptive immune response in antigen-induced inflammation in mice, focusing on its effects on B cells and B cell subsets.

Oxidative processes during enzymatic hydrolysis of cod protein and their influence on antioxidant and immunomodulating ability.

Fish protein hydrolysates (FPH) have many desirable properties, however heating and shifts in pH can cause oxidation during enzymatic hydrolysis. The objective was to investigate oxidative processes during enzymatic hydrolysis of fish protein and the impact of oxidation on the antioxidant and immunomodulating ability of FPH. Protease P "Amano" 6 was used to hydrolyze cod protein in the presence and absence of pro-oxidants at pH 8 and 36°C to achieve 20% degree of hydrolysis.

Dietary fish oil reduces the acute inflammatory response and enhances resolution of antigen-induced peritonitis.

Dietary n-3 polyunsaturated fatty acids (PUFA) influence the inductive phase of inflammation but less is known about their effects on the resolution phase. This study examined the effects of dietary fish oil on induction and resolution of antigen-induced inflammation in mice. Mice were fed a control diet with or without 2.