Cyclooxygenase Activity Is Increased in Platelets from Psoriatic Patients

Vilá, Luis M.; Cullaré, C; Solá, Josep; Puig, L.; Castellarnau, Conxita de; Moragas, J. M. De

doi:10.1111/1523-1747.ep12491695

Cited by 24 publications

(18 citation statements)

References 27 publications

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“…Evidence for platelet activation, however, is well established in psoriasis, a chronic inflammatory skin disease (Berrettini et al, 1985;Hayashi et al, 1985;Vila et al, 1991). Our data on increased platelet P-selectin expression in patients with psoriasis further support this notion.…”

Section: Figuresupporting

confidence: 79%

Activated, Not Resting, Platelets Increase Leukocyte Rolling in Murine Skin Utilizing a Distinct Set of Adhesion Molecules

Ludwig

Schultz

Boehncke

et al. 2004

Journal of Investigative Dermatology

115

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Selectin-mediated tethering and rolling initiates the multi-step process of leukocyte extravasation which is crucial for the formation of an inflammatory infiltrate. We studied the impact of platelets on this process in the skin. Using intravital microscopy, we analyzed platelet interactions with cutaneous post-capillary venules of mouse ears and observed an increase in platelet rolling if platelets were activated (41.6+/-20.2% vs. 13.1+/-8.5% rolling of resting platelets). Experiments with P-selectin deficient mice and antibodies blocking either P-selectin, GPIIb/IIIa or GPIb showed that rolling depends on platelet PSGL-1 and GPIIb/IIIa on one hand, and endothelial P-selectin on the other. Next, formation of platelet-leukocyte aggregates was demonstrated by simultaneous observation of platelets and leukocytes in vivo utilizing a newly developed two-color technique. Aggregates increased overall leukocyte rolling (leukocytes alone: 27.4+/-11.2%, leukocytes with resting platelets: 25.3+/-10.2%, leukocytes with activated platelets 38.1+/-11.8%). To investigate if activated platelets may contribute to the pathogenesis of chronic cutaneous inflammation, platelet P-selectin expression was studied in 8 patients with psoriasis. A correlation between platelet P-selectin expression and disease severity was established. In summary, we show that activated, not resting, platelets increase leukocyte rolling in murine skin. This increased rolling is due to the aggregate formation of platelets with leukocytes. We also provide evidence for a potential role of this mechanism in the pathogenesis of chronic inflammatory skin diseases.

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Section: Figuresupporting

confidence: 79%

Activated, Not Resting, Platelets Increase Leukocyte Rolling in Murine Skin Utilizing a Distinct Set of Adhesion Molecules

Ludwig

Schultz

Boehncke

et al. 2004

Journal of Investigative Dermatology

115

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“…COX inhibition assays were done in human platelet suspensions prepared as described previously (28). Drugs were added to 175 AL of platelet suspensions, adjusted to a density of 170 Â 10 6 platelets/mL and incubated at 37jC for 5 minutes prior to the addition of substrate.…”

Section: Methodsmentioning

confidence: 99%

Novel triiodophenol derivatives induce caspase-independent mitochondrial cell death in leukemia cells inhibited by Myc

Parreño

Vaqué²,

Casanova³

et al. 2006

Molecular Cancer Therapeutics

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Abstract2,4,6-Triiodophenol (Bobel-24, AM-24) was originally described as a nonsteroid antiinflammatory molecule. We have synthesized three derivatives of and tested their activities as putative antileukemic agents. We have found that Bobel-24 and Bobel-16 were dual inhibitors of cyclooxygenase and 5-lipoxygenase, whereas Bobel-4 and Bobel-30 were selective against 5-lipoxygenase. We have tested the antiproliferative activity of these compounds on a panel of cell lines derived from myeloid and lymphoid leukemias (K562, Raji, HL-60, and Molt4). The cytotoxic IC 50 in these cell lines ranged between 14 and 50 Mmol/L, but it was higher for nontransformed cells such as 32D, NIH3T3, or human leukocytes. All compounds showed cytotoxic activity on all tested cell lines, accompanied by DNA synthesis inhibition and arrest in the G 0 /G 1 phase. Bobel-16, Bobel-4, and Bobel-24 induced a caspase-independent cell death in K562 and Raji cells, accompanied by chromatin condensation, cytochrome c release, and dissipation of mitochondrial membrane potential in a concentration-dependent manner and production of reactive oxygen species. As the proto-oncogene MYC is involved in mitochondrial biogenesis and survival of leukemia cells, we tested its effect on bobel activity. Bobel-24 induced down-regulation of MYC in K562 and, consistently, ectopic expression of MYC results in partial protection towards the cytotoxic effect of Bobel-24. In conclusion, Bobel derivatives induce a caspase-and Bcl-2-independent cell death in which mitochondrial permeabilization and MYC down-regulation are involved. Bobels may serve as prototypes for the development of new agents for the therapy of leukemia. [Mol Cancer Ther 2006;5(5):1166-75]

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“…Platelet-rich plasma (PRP) was obtained from peripheral venous blood drawn from healthy nonsmoker adult donors who had not received any medication for 2 weeks prior to the extraction as described before (41). PRP was adjusted to 0.25 3 10 6 cells/ml with autologous platelet-poor plasma for aggregation assays.…”

Section: Platelet Aggregation Experimentsmentioning

confidence: 99%

“…In vitro platelet aggregation in response to 0.8 mmol/l AA (Diamed, Switzerland) was performed in an Automatic Platelet Aggregation Analyzer, PA-3220 (AGGRECORDER II, Menarini) as described previously (41,42). Prior to aggregation onset, 50 ml of HUVEC suspensions was added to 400 ml of PRP and left to stand at 37°C for 5 min.…”

Section: Platelet Aggregation Experimentsmentioning

confidence: 99%

Retinoic acid induces PGI synthase expression in human endothelial cells

Camacho

Rodrı́guez

Salazar

et al. 2008

Journal of Lipid Research

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Retinoic acid (RA) exhibits anti-inflammatory, anti-tumor, and immuno-modulatory actions, and affects angiogenesis and thrombosis. Arachidonic acid (AA) metabolites are involved in all these processes. We explored the effect of RA on AA metabolism in human umbilical vein endothelial cells (HUVECs). 13-cis -RA increased the release of prostaglandin I 2 (PGI 2) , both spontaneous and thrombin-induced, in terms of 6-oxo-PGF 1a analyzed by enzyme-immunoassay. Coincubation with 13-cis-RA and interleukin-1b resulted in a synergic increase in the release of PGI 2 . Consistently, 13-cis -RA increased the ability of HUVECs to inhibit AA-induced platelet aggregation. 13-cis-RA did not induce cyclooxygenase-isoenzyme expression, determined by immunoblotting, or activity, evaluated by analyzing eicosanoids formed from exogenous labeled AA by HPLC. In contrast, RA induced PGI synthase (PGIS) activity and expression in terms of mRNA and protein determined by real-time PCR and Western blotting, respectively. Results from experiments with several species of RA and with retinoic acid receptor (RAR) and retinoid X receptor (RXR) antagonists showed that the effect of RA on PGIS expression was mediated by RAR. Actinomycin D and cycloheximide both inhibited RA-induced PGIS expression. Furthermore, RA increased PGIS transcriptional activity in transient transfection assays, an effect that was prevented by an RAR antagonist. These results reinforce the concept that RA could be beneficial for patients with cardiovascular risk.-Camacho, M., C. Rodríguez, J. Salazar, J. Martínez-González, J. Ribalta, J-R. Escudero, L. Masana, and L. Vila. Retinoic acid induces PGI synthase expression in human endothelial cells.

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Cyclooxygenase Activity Is Increased in Platelets from Psoriatic Patients

Cited by 24 publications

References 27 publications

Activated, Not Resting, Platelets Increase Leukocyte Rolling in Murine Skin Utilizing a Distinct Set of Adhesion Molecules

Activated, Not Resting, Platelets Increase Leukocyte Rolling in Murine Skin Utilizing a Distinct Set of Adhesion Molecules

Novel triiodophenol derivatives induce caspase-independent mitochondrial cell death in leukemia cells inhibited by Myc

Retinoic acid induces PGI synthase expression in human endothelial cells

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