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In Vitro Digested Nut Oils Attenuate the Lipopolysaccharide-Induced Inflammatory Response in Macrophages.

ABSTRACT: Nut consumption is known for its health benefits, in particular in inflammatory diseases. A possible mechanism for these effects could be their beneficial fatty acid composition. Nuts mainly contain mono- and polyunsaturated fatty acids, which have anti-inflammatory properties. However, studies investigating the effects of nut extracts on inflammatory processes on the molecular level are rare. We therefore prepared oily nut extracts after in vitro digestion and saponification of the fat-soluble constituents. Besides chromatographic analysis, cell culture experiments were performed using murine macrophages (RAW264.7) to study the capacity of different nut extracts (hazelnut, almond, walnut, macadamia, and pistachio) to modulate inflammatory processes. Oleic acid was the main fatty acid in hazelnut, almond, macadamia, and pistachio extracts. Both oily nut extracts and pure oleic acid significantly reduced the LPS-induced expression of iNos, Cox2, Tnf?, Il1?, and Il6 mRNAs. iNos protein expression was down-regulated followed by reduced nitric oxide formation. Thus, nut extracts at concentrations achievable in the digestive tract inhibit the expression and formation of inflammatory mediators in macrophages. Hence, a beneficial contribution of nut consumption to inflammatory diseases can be assumed. We are convinced that these results provide new insights on the molecular mechanisms involved in the health-beneficial effects of nuts.

SUBMITTER: Muller AK

PROVIDER: S-EPMC6471109 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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In Vitro Digested Nut Oils Attenuate the Lipopolysaccharide-Induced Inflammatory Response in Macrophages.

Müller Anke Katharina AK Schmölz Lisa L Wallert Maria M Schubert Martin M Schlörmann Wiebke W Glei Michael M Lorkowski Stefan S

Nutrients 20190227 3

Nut consumption is known for its health benefits, in particular in inflammatory diseases. A possible mechanism for these effects could be their beneficial fatty acid composition. Nuts mainly contain mono- and polyunsaturated fatty acids, which have anti-inflammatory properties. However, studies investigating the effects of nut extracts on inflammatory processes on the molecular level are rare. We therefore prepared oily nut extracts after in vitro digestion and saponification of the fat-soluble ...[more]

PMID: 30818812

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Project description:Previous studies have revealed that activation of the Toll‑like receptor 4 (TLR4)‑mediated proinflammatory signaling pathway plays an important role in acute inflammation, sepsis and chronic inflammatory disorders. Moreover, TLR4 significantly contributes to lipopolysaccharide (LPS)‑induced immune response. Thus, modulation of the TLR4 pathway is an important strategy to specifically target these pathologies. The aim of the present study was to develop a complete human anti‑TLR4 IgG2 antibody by screening human TLR4 Fab from a phage‑display library and integrating it with constant regions of the heavy chain of human IgG2 via antibody engineering. ELISA, a BLItz system and fluorescence‑activated cell sorting were used to assess its affinity. Furthermore, mouse‑derived peritoneal macrophages were treated with human anti‑TLR4 IgG2 and induced with LPS in vitro. Reverse transcription‑quantitative PCR and western blotting were used to determine mRNA expression levels of cytokines and phosphorylation levels of signaling pathways, respectively. It was found that human anti‑TLR4 IgG2 bound to TLR4 with a high affinity of 8.713x10‑10 M, and that preincubation with anti‑TLR4 IgG2 inhibited the LPS‑induced production of tumor necrosis factor‑α, interferon‑β and interleukin‑6 mRNA expression levels in mouse peritoneal macrophages. It was also demonstrated that human anti‑TLR4 IgG2 inhibited LPS‑induced TLR4 signaling by reducing the phosphorylation of the NF‑κB, mitogen‑activated protein kinase and interferon regulatory factor 3 signaling pathways. In addition, human anti‑TLR4 IgG2 protected mice from LPS challenge with a survival rate of 40% and also significantly increased the survival time in the cecal ligation and puncture model. Therefore, it was speculated that human anti‑TLR4 IgG2 plays a protective role against sepsis‑associated injury and is potentially applicable for the treatment of infection‑associated immune dysfunction.

Project description:Acute-on-chronic liver injury is characterized by an important inflammatory response frequently associated with endotoxemia. In this context, acute-phase proteins such as Pentraxin-3 (PTX3) are released; however, little is known about their role in chronic liver disease. The aim of this study was to elucidate the role of PTX3 in liver injury. The role of PTX3 was evaluated in cultured human cells, liver tissue slices, and mice with acute-on-chronic liver injury. PTX3 expression was assessed in tissue and serum samples from 54 patients with alcoholic hepatitis. PTX3 expression was up-regulated in animal models of liver injury and strongly induced by lipopolysaccharide (LPS). Liver cell fractionation showed that macrophages and activated hepatic stellate cells were the main cell types expressing PTX3 in liver injury. Ex vivo and in vivo studies showed that PTX3 treatment attenuated LPS-induced liver injury, inflammation, and cell recruitment. Mechanistically, PTX3 mediated the hepatic stellate cell wound-healing response. Moreover, PTX3 modulated LPS-induced inflammation in human primary liver macrophages and peripheral monocytes by enhancing a TIR domain-containing adapter-inducing interferon-dependent response and favoring a macrophage interleukin-10-like phenotype. Additionally, hepatic and plasma PTX3 levels were increased in patients with alcoholic hepatitis, a prototypic acute-on-chronic condition; and its expression correlated with disease severity scores, endotoxemia, infections, and short-term mortality, thus suggesting that expression of PTX3 found in patients could be a counterregulatory response to injury.ConclusionExperimental and human evidence suggests that, in addition to being a potential biomarker for alcoholic hepatitis, PTX3 participates in the wound-healing response and attenuates LPS-induced liver injury and inflammation; therefore, administration of PTX3 could be a promising therapeutic strategy in acute-on-chronic conditions, particularly those associated with endotoxemia. (Hepatology 2017;66:953-968).

Dataset Information

In Vitro Digested Nut Oils Attenuate the Lipopolysaccharide-Induced Inflammatory Response in Macrophages.

Publications

In Vitro Digested Nut Oils Attenuate the Lipopolysaccharide-Induced Inflammatory Response in Macrophages.

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