34 research outputs found
Age-dependent disruption of murine lung microvascular endothelial barrier integrity by platelet-derived TGFβ1: an effect of platelet releasate milieu - raw data
No full textThe set of raw data obtained within the project funded by the National Science Center, OPUS 21 (project no 2021/41/B/NZ5/02374) associated with age-dependent regulation of murine lung microvascular endothelial barrier integrity by platelet releasates with active and non-active platelet-derived TGFbeta
Characterisation of the Fpr2 null mouse
No full textPhDA novel Fpr2-/- mouse colony was used to explore the biology of Fpr2, a GPCR
related to the human FPR2/ALX receptor that recognises lipoxin A4 (LXA4)
annexin A1 (AnxA1) and serum amyloid A (SAA). Southern blotting, PCR and
radio-ligand binding confirmed receptor deletion in the mouse Fpr2-/- colony.
A GFP target/reporter strategy was employed in generating this novel transgenic
to monitor promoter activity in living cells. This study revealed a propensity of
Fpr2 for granulocytes, as well as a distinct role in macrophage (Mφ) maturation.
Characterisation of Fpr2-/- Mφ revealed selective ERK phosphorylation triggered
by the AnxA1-derived peptide Ac2-26, W peptide and Compound 43 (C43).
Despite this Fpr-dependent signalling cascade via ERK, it was not a functional
prognostic for cell migration in vitro or in vivo. Formyl peptide (fMLP) and serum
amyloid A (SAA) chemotactic action was attenuated in Fpr2-/- Mφ, as well as the
pro-phagocytic effects of Ac2-26 and LXA4.
There was no observable naïve phenotype associated with Fpr2 depletion. To
investigate the patho-physiology of Fpr2, acute and chronic inflammatory models
were investigated in vivo to dissect different aspects of the receptor during
disease progression. Notably Fpr2-/- mice exhibited stimulus specific
discrepancies in inflammatory response. An acute IL-1β-induced air pouch model
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revealed predominantly anti-migratory pharmacology of Fpr2 ligands, with a
notable exception of SAA, discovered to be anti-migratory in the absence of Fpr2.
Analysis of the full time-course of the zymosan peritonitis pointed to a subtle role
for Fpr2 in neutrophil and monocyte migration as well as Mφ maturation. Of
interest, exudate levels of SAA were augmented in Fpr2-/- mice revealing complex
regulatory receptor/ligand circuits active during on-going inflammatory reactions.
Finally, Fpr2-/- mice displayed pronounced arthritic responses upon treatment with
the K/BxN arthrogenic serum, in comparison to their wild type controls. We
conclude that Fpr2 can serve varied regulatory functions during the host response
to inflammatory insult
Up-Regulation of Annexin-A1 and Lipoxin A(4) in Individuals with Ulcerative Colitis May Promote Mucosal Homeostasis
No full textPubMed ID: 22723974This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Extreme ultraviolet emission lines of Ni XII in laboratory and solar spectra
No full textWavelengths for emission lines arising from 3s23p5-3s3p6 and 3s23p5-3s23p43d transitions in Ni XII have been measured in extreme ultraviolet spectra of the Joint European Torus(JET) tokamak. The 3s23p5 2P1/2-3s23p4(3P)3d 2D3/2 line is found to lie at 152.90 ± 0.02 A, a significant improvement over the previous experimental determination of 152.95 ± 0.5 A. This new wavelength is in good agreement with a solar identification at 152.84 ± 0.06 A, confirming the presence of this line in the solar spectrum. The Ni XII feature at 152.15 A may be a result only of the 3s23p5 2P3/2-3s23p4(3P)3d 2D5/2 transition, rather than a blend of this line with 3s23p5 2P3/2-3s23p (3P)3d 2P1/2, as previously suggested. Unidentified emission
lines at 295.32 and 317.61 A in solar flare spectra from the Skylab mission are tentatively identified as the 3s23p5 2P3/2-3s3p6 2S1/2 and 3s23p5 2P1/2-3s3p6 2S1/2 transitions in Ni XII, which have laboratory wavelengths of 295.33 and 317.50 A, respectively. Additional support for these identifications is provided by the line intensity ratio for the solar features, which shows good agreement between theory and observation
Investigation of cardiac fibroblasts using myocardial slices
No full textAims
Cardiac fibroblasts (CFs) are considered the principal regulators of cardiac fibrosis. Factors that influence CF activity are difficult to determine. When isolated and cultured in vitro, CFs undergo rapid phenotypic changes including increased expression of α-SMA. Here we describe a new model to study CFs and their response to pharmacological and mechanical stimuli using in vitro cultured mouse, dog and human myocardial slices.
Methods and results
Unloading of myocardial slices induced CF proliferation without α-SMA expression up to 7 days in culture. CFs migrating onto the culture plastic support or cultured on glass expressed αSMA within 3 days. The cells on the slice remained αSMA(−) despite transforming growth factor-β (20 ng/ml) or angiotensin II (200 µM) stimulation. When diastolic load was applied to myocardial slices using A-shaped stretchers, CF proliferation was significantly prevented at Days 3 and 7 (P < 0.001).
Conclusions
Myocardial slices allow the study of CFs in a multicellular environment and may be used to effectively study mechanisms of cardiac fibrosis and potential targets
Interleukin 17 sustains rather than induces inflammation
No full textInterleukin (IL)17 is a novel cytokine that has been suggested to play a key role in sustaining chronic inflammation in autoimmune diseases. Since its discovery, much attention has been given to mediators and factors responsible for the development of IL-17-producing cells while very few studies have investigated the inflammatory properties of this cytokine. Here we aimed to characterize the inflammatory properties of IL-17 and to establish if this cytokine per se can initiate an inflammatory reaction or if its main role is to contribute to the exacerbation of ongoing inflammation. To this aim we used two different mouse models of inflammation: the paw oedema and the airpouch. Interestingly, injection of IL-17 in the hind paw did not cause oedema while administration in the pre-inflamed tissues of 6-day-old air pouches induced a long lasting inflammatory reaction that was sustained between 4 and 24h post-injection. Phenotypic analysis of cellular infiltrates demonstrated selective PMN recruitment in exudates and pouch lining tissues. This event was accompanied by induction of a distinct set of pro-inflammatory cytokines including IL-1beta, IL-6, TNF-alpha and chemokines KC and MCP-1. Co-administration of a neutralizing anti-KC antibody with IL-17 significantly reduced its inflammatory response suggesting a key role for this chemokine in mediating the inflammatory effects of IL-17. In conclusion these results demonstrate that IL-17 does not initiate an inflammatory reaction while, if injected in pre-inflamed tissues, is able to further amplify biochemical and cellular events characteristic of the early stages of the inflammatory reaction.</p
FPR2/ALX receptor expression and internalization are critical for lipoxin A<sub>4</sub>and annexin‐derived peptide‐stimulated phagocytosis
No full textBS6 Endothelial-specific ERG deletion leads to dramatic reduction in cardiopulmonary function
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