IL-1β Stimulates COX-2 Dependent PGE2 Synthesis and CGRP Release in Rat Trigeminal Ganglia Cells

OBJECTIVE: Pro-inflammatory cytokines like Interleukin-1 beta (IL-1β) have been implicated in the pathophysiology of migraine and inflammatory pain. The trigeminal ganglion and calcitonin gene-related peptide (CGRP) are crucial components in the pathophysiology of primary headaches. 5-HT1B/D receptor agonists, which reduce CGRP release, and cyclooxygenase (COX) inhibitors can abort trigeminally mediated pain. However, the cellular source of COX and the interplay between COX and CGRP within the trigeminal ganglion have not been clearly identified. METHODS AND RESULTS: 1. We used primary cultured rat trigeminal ganglia cells to assess whether IL-1β can induce the expression of COX-2 and which cells express COX-2. Stimulation with IL-1β caused a dose and time dependent induction of COX-2 but not COX-1 mRNA. Immunohistochemistry revealed expression of COX-2 protein in neuronal and glial cells. 2. Functional significance was demonstrated by prostaglandin E2 (PGE(2)) release 4 hours after stimulation with IL-1β, which could be aborted by a selective COX-2 (parecoxib) and a non-selective COX-inhibitor (indomethacin). 3. Induction of CGRP release, indicating functional neuronal activation, was seen 1 hour after PGE(2) and 24 hours after IL-1β stimulation. Immunohistochemistry showed trigeminal neurons as the source of CGRP. IL-1β induced CGRP release was blocked by parecoxib and indomethacin, but the 5-HT1B/D receptor agonist sumatriptan had no effect. CONCLUSION: We identified a COX-2 dependent pathway of cytokine induced CGRP release in trigeminal ganglia neurons that is not affected by 5-HT1B/D receptor activation. Activation of neuronal and glial cells in the trigeminal ganglion by IL-β leads to an elevated expression of COX-2 in these cells. Newly synthesized PGE(2) (by COX-2) in turn activates trigeminal neurons to release CGRP. These findings support a glia-neuron interaction in the trigeminal ganglion and demonstrate a sequential link between COX-2 and CGRP. The results could help to explain the mechanism of action of COX-2 inhibitors in migraine

Integrated compounding processes using supercritical carbon dioxide

Todays compounding technology allows flexible processing of polymer compounds and blends. Nevertheless the trend to use tailored compounds results in an increasing demand for more flexible and efficient polymer-modification processes. Integrated compounding processes using supercritical carbon dioxide (scCO2) are an interesting option to increase flexibility in the compounding process, because scCO2 has interesting properties for polymer compounding, offering solubility for additives as well as for unwanted contaminations in polymers and can therefore act as a carrier for these substances for chemical modification or cleaning processes. The combination of both, compounding and high pressure technology for supercritical carbon dioxide in a specially designed twin screw extruder offers therefore completely new ways to process polymers. First results indicate that this allows effective cleaning processes where carbon dioxide is used as an environmental friendly solvent and carrier

Synthesis of polymers with phosphorus containing side chains via modular conjugation

Polystyrene-based copolymers synthesized by RAFT polymerization of 4-vinylbenzyl chloride (4-VBC) and styrene with subsequent azide transformation are used to prepare phosphorylated polymers via 1,3-dipolar cycloaddition with diphenyl prop-2-ynyl phosphoric ester (DPPP). To avoid metal salts in the reaction mixture of the 1,3-dipolar cycloaddition, a novel metal free approach was developed to synthesize DPPP. The successful conversion to phosphorylated polymers is confirmed by X-ray photoelectron spectroscopy (XPS), infrared (IR) spectroscopy as well as solid phase nuclear magnetic resonance (NMR) spectroscopy. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) are employed to determine the influence of the phosphoric ester on the thermal properties of the generated polymers. Through a series of TGA-MS measurements, the decomposition products of the phosphorylated polymers, e. g. styrene, phenyl, alkyne and diphenyl phosphite moieties, are determined

Linear and nonlinear rheological behavior and crystallization of semicrystalline poly(styrene)-poly(L-lactide) block copolymers

The rheological behavior of a poly(styrene)-poly(L-lactide) (PS-PLLA) block copolymer was investigated in the viscoelastic linear and nonlinear regime. Large amplitude oscillatory shear (LAOS) experiments in the nonlinear regime led to an exponential decay of the G moduli and the nonlinearity parameter I-3/1. During LAOS, the lamellar microstructure of a low molecular weight PS-PLLA copolymer was orientated parallel to the shear field to achieve a macroscopically ordered material. The degree of orientation was analyzed via small angle X-ray scattering (SAXS) measurements. The crystallization kinetics could be accurately described by the Avrami equation as determined by DSC and rheology. These experiments revealed that the crystallization process was slower for the PS-PLLA copolymers than for the PLLA homopolymers. SAXS was also used to monitor the crystallization of the PS-PLLA copolymers. When the temperature of the crystallization experiments, T-c, was lower than the glass transition temperature of the amorphous PS block, 7; (hard confinement), the lamellar microstructure of the low molecular weight PS-PLLA was maintained apart from a small increase in the domain spacing. When T-c was higher than T-g(a) of PS (soft confinement), the block copolymer also retained its lamellar structure, but the increase in the domain spacing was unexpectedly increased compared to what occurred for crystallization under hard confinement conditions. In addition, two-dimensional (2-D) SAXS diffractograms indicated a loss of the structure periodicity during crystallization under soft confinement

Continuous hydrothermal synthesis of in situ functionalized iron oxide nanoparticles: A general strategy to produce metal oxide nanoparticles with clickable anchors

A study was conducted to demonstrate continuous hydrothermal synthesis of in situ functionalized iron oxide nanoparticles, using a general strategy to produce metal oxide nanoparticles with clickable anchors. The design of bifunctional molecules that combine a robust anchor that bound to a variety of metal oxide surfaces and a second functional group that led to covalent attachment of molecules via click chemistry, was proposed as a strategy to introduce a broad range of functionalities onto the surfaces of metal oxide nanoparticles. The strategy was applicable to a tremendous diversity of molecules including functional polymers, biomolecules, fluorescent dyes and molecular anchors. The investigations were started with molecules containing a terminal alkyne group allowing straightforward coupling with azide-terminated molecules via the most used and well-known click reaction.</p

Leichtbau durch funktionsintegrierende Strukturen in Multi Material Design - hybride Sandwichbauweisen für Schienenfahrzeuge : PURtrain ; Abschlussbericht des Forschungsvorhabens

Das diesem Bericht zugrundeliegende Vorhaben wurde mit Mitteln des Bundesministeriums für Bildung und Forschung unter dem Förderkennzeichen 03X3019 gefördert

Abschlussbericht zum Verbundvorhaben "Neuartige Polymere auf Basis von Triglyceriden" : Darstellung der erzielten Ergebnisse für die Teilvorhaben mit den Partnern ; Teilvorhaben 1: Entwicklung von Katalysatoren und Herstellung neuer Monomere, Leibniz-Institut für Katalyse e.V. an der Universität Rostock (LITKAT) ; Teilvorhaben 2: Herstellung der Polyamide und Polyurethane, Fraunhofer-Institut für Chemische Technologie (ICT) ; Teilvorhaben 3: Entwicklung von Verfahren zur Herstellung von Monomeren für Kunststoffe aus plfanzlichen Ölsäuren, Evonik Oxeno GmbH (Oxeno) ; Teilvorhaben 4: Herstellung der Polyamide sowie Bewertung, Evonik Degussa GmbH (High Performance Polymers [HPP]) ; Teilvorhaben 5: Herstellung der Polyurethane sowie Bewertung und Dokumentation, Rampf Ecosystems GmbH & Co KG ; Laufzeit des Vorhabens/Berichtszeitraum: 01.10.2008 bis 31.12.2011

[no abstract available