Acute and chronic inflammatory disorders are characterized by detrimental cytokine and chemokine expression. Frequently, the chemotactic activity of cytokines depends on a modified N-terminus of the polypeptide. Among those, the N-terminus of monocyte chemoattractant protein 1 (CCL2 and MCP-1) is modified to a pyroglutamate (pE-) residue protecting against degradation in vivo. Here, we show that the N-terminal pE-formation depends on glutaminyl cyclase activity. The pE-residue increases stability against N-terminal degradation by aminopeptidases and improves receptor activation and signal transduction in vitro. Genetic ablation of the glutaminyl cyclase iso-enzymes QC (QPCT) or isoQC (QPCTL) revealed a major role of isoQC for pE1-CCL2 formation and monocyte infiltration. Consistently, administration of QC-inhibitors in inflammatory models, such as thioglycollate-induced peritonitis reduced monocyte infiltration. The pharmacologic efficacy of QC/isoQC-inhibition was assessed in accelerated atherosclerosis in ApoE3*Leiden mice, showing attenuated atherosclerotic pathology following chronic oral treatment. Current strategies targeting CCL2 are mainly based on antibodies or spiegelmers. The application of small, orally available inhibitors of glutaminyl cyclases represents an alternative therapeutic strategy to treat CCL2-driven disorders such as atherosclerosis/restenosis and fibrosis.

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Hazelnuts are rarely cultivated in Germany, although they are a valuable source for macro- and micronutrients and can thus contribute to a healthy diet. Near the present, 15 varieties were cultivated in Thuringia, Germany, as a pilot study for further research. The aim of our study was to evaluate the micro- and macronutrient composition of representative, randomly mixed samples of the 15 different hazelnut cultivars. Protein, fat, and fiber contents were determined using established methods. Fatty acids, tocopherols, minerals, trace elements, and ultra-trace elements were analyzed using gas chromatography, high-performance liquid chromatography, and inductively coupled plasma triple quadrupole mass-spectrometry, respectively. We found that the different hazelnut varieties contained valuable amounts of fat, protein, dietary fiber, minerals, trace elements, and α-tocopherol, however, in different quantities. The variations in nutrient composition were independent of growth conditions, which were identical for all hazelnut varieties. Therefore, each hazelnut cultivar has its specific nutrient profile.

Olive oil contains high amounts of oleic acid (OA). Although OA has been described to inhibit inflammatory processes, the effects of olive oil on cellular mechanisms remain poorly understood. Therefore, we compared the effects of major fatty acids (FA) from olive oil with those of olive oil extracts (OOE) on inflammatory mediators and alterations in the cellular phospholipid composition in murine macrophages. Upon treatment with different OOE, FA compositions of lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages were analyzed using gas chromatography. Olive oil extracts and OA significantly reduced the LPS-induced expression of inducible nitric oxide synthase (iNos), cyclooxygenase (Cox2), and interleukin-6 mRNA. In addition, a significant decrease in Cox2 and iNos protein expression was observed. The formation of nitric oxide was significantly reduced, while the formation of prostaglandin (PG) E2 from arachidonic acid significantly increased after treatment with OOE or OA. The latter was associated with a shift in the phospholipid FA composition from arachidonic acid to OA, resulting in an elevated availability of arachidonic acid. Together, OOE and OA mediate anti-inflammatory effects in vitro but increase the release of arachidonic acid and hereinafter PGE2, likely due to elongation of OA and competitive incorporation of fatty acids into membrane phospholipids.