Search results for "N-2"
showing 10 items of 1881 documents
Anandamide inhibits IL-12p40 production by acting on the promoter repressor element GA-12: Possible involvement of the COX-2 metabolite prostamide E 2
2007
The eCB [endoCB (cannabinoid)] system is being considered as a novel therapeutic target for immune disorders. Cytokines of the IL-12 (interleukin-12) family have essential functions in cell-mediated immunity. In the present study, we have addressed the mechanisms of action of the eCB AEA (anandamide) on the regulation of IL-12p40 in activated microglia/macrophages. We demonstrated that AEA can inhibit the expression of p35, p19 and p40 subunits, which form the biologically-active cytokines IL-12 and IL-23 in microglia stimulated with LPS (lipopolysaccharide)/IFNγ (interferon γ). Additionally, we have provided evidence that AEA reduces the transcriptional activity of the IL-12p40 gene in LPS…
Evaluation of soluble CD 14 and neopterin as serum parameters of the inflammatory activity of pulmonary sarcoidosis.
1992
CD14 represents the most specific marker for monocytes/macrophages. It has been demonstrated in vitro that monocytes/macrophages lose this antigen upon activation. Results of studies investigating the expression of membrane-bound CD14 on the surface of monocytes/macrophages in sarcoidosis patients are controversial. To investigate whether the soluble form of CD14 reflects monocyte/macrophage activation in sarcoidosis, serum levels of soluble CD14 were determined concurrently with other serum markers of monocyte/macrophage activation (neopterin, angiotensin-converting enzyme) in 50 consecutive patients with bioptically confirmed sarcoidosis. The patients were allocated to three groups accord…
Interferon-α Suppresses cAMP to Disarm Human Regulatory T Cells
2013
Abstract IFN-α is an antineoplastic agent in the treatment of several solid and hematologic malignancies that exerts strong immune- and autoimmune-stimulating activity. However, the mechanisms of immune activation by IFN-α remain incompletely understood, particularly with regard to CD4+CD25highFoxp+ regulatory T cells (Treg). Here, we show that IFN-α deactivates the suppressive function of human Treg by downregulating their intracellular cAMP level. IFN-α–mediated Treg inactivation increased CD4+ effector T-cell activation and natural killer cell tumor cytotoxicity. Mechanistically, repression of cAMP in Treg was caused by IFN-α–induced MAP–ERK kinase (MEK)/extracellular signal-regulated ki…
P38 MAP Kinase Signaling Is Required for the Conversion of CD4+CD25− T Cells into iTreg
2008
CD4+CD25+ regulatory T cells (Treg) are important mediators of immune tolerance. A subset of Treg can be generated in the periphery by TGF-beta dependent conversion of conventional CD4+CD25− T cells into induced Treg (iTreg). In chronic viral infection or malignancy, such induced iTreg, which limit the depletion of aberrant or infected cells, may be of pathogenic relevance. To identify potential targets for therapeutic intervention, we investigated the TGF-beta signaling in Treg. In contrast to conventional CD4+ T cells, Treg exhibited marked activation of the p38 MAP kinase pathway. Inhibition of p38 MAP kinase activity prevented the TGF-beta-dependent conversion of CD4+CD25− T cells into …
3,5-Diaizvietotu-4-fenil-2-pirolidonu un to strukturālo analogu sintēze
2017
5-Alkil-4-fenil-3-metilēn-2-pirolidonu un to strukturālo analogu sintēze. Baškevičs V., Darba vadītājs: Dr. ķīm. Maksims Vorona. Maģistra darbs. 102 lappuses, 18 attēli, 30 pielikumi, 32 literatūras avoti. Latviešu valodā. Uz Morita-Baylis-Hillman reakcijas produktu bāzes realizēta to acilēšana un nitroalkānu pievienošanas starpproduktam. Iegūtie starpprodukti tika pakļauti reducēšanas reakcijai un iekšmolekulārai ciklizācijai ar eksometilēn grupu saturošo 2-pirolidonu veidošanu. Šim nolūkam bija izmēģinātas vairākas literatūrā eksistējošas 5-alkil-4-fenil-3-metilēn-2-pirolidonu iegūšanas metodes, no kuriem tika izvēlēta reducēšanas reakcija ar dzelzs pulvera palīdzību ledus etiķskābē. Iegū…
Macromolecular Prodrugs Based on Synthetic Polyaminoacids: Drug Delivery and Drug Targeting in Antitumor Therapy
2011
In the last twenty years a depth study on potential pharmaceutical applications of synthetic polymers at proteinlike structure as carrier for macromolecular prodrug production has been performed in academia and in industry. In particular α,β-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA), α,β-polyaspartylhydrazide (PAHy), poly(glutamic acid) (PGA), poly(aspartic acid) (PAA) and polylysine (PLL) have been extensively studied in this field. In the present review, the use of PHEA, PAHy, PGA as starting materials to prepare macromolecular prodrugs is reported and drug delivery and targeting aspects have been considered.
The role of Interleukin-2 during the activation of cytotoxic T-lymphocytes
1983
Der vorliegende Artikel stellt eine Ubersicht dar Uber die derzeitigen Vorstellungen des Zusammenwirkens zellularer und humoraler Faktoren, die zu T-Zell-vermittelten zytotoxischen Immunreaktionen fuhren. Da im Ablauf derartiger Immunreaktionen hormonahnliche Wachstumsfaktoren (interleukine) eine entscheidende Rolle spielen, liegt der Schwerpunkt der Diskussion auf der Beschreibung dieser Mediatoren; insbesondere wird die Bedeutung von Interleukin-2 (Il-2) diskutiert. Il-2 ist ein losliches, nicht antigenspezifisches Glykoprotein mit einem Molekulargewicht von 15 000 Dalton (humanes Il-2) bzw. 30 000 Dalton (murines Il-2). Es wird in vitro von T-Helfer-Lymphozyten sezerniert, die in der Mau…
Pegylated nanoparticles based on a polyaspartamide. Preparation, physico-chemical characterization and intracellular uptake
2006
Nanoparticles with different surface PEGylation degree were prepared by using as starting material alpha,beta-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA). PHEA was functionalized with a PEG amino-derivative for obtaining PHEA-PEG(2000) copolymer. Both PHEA and PHEA-PEG(2000) were derivatized with methacrylic anhydride (MA) for obtaining poly(hydroxyethylaspartamide methacrylated) (PHM) and poly(hydroxyethylaspartamide methacrylated)-PEGylated (PHM-PEG(2000)), respectively. Nanoparticles were obtained by UV irradiation of an inverse microemulsion, using as internal phase an aqueous solution of PHM alone or of the PHM/PHM-PEG(2000) mixture at different weight ratio and as external phase a m…
ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion
2015
Abstract There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS ca…
Intraperitoneal administration of the anti-IL-23 antibody prevents the establishment of intestinal nematodes in mice
2018
AbstractPrevious studies have established that an increased Th-9 response creates a hostile environment for nematode parasites. Given that IL-23, a cytokine required for maintenance of the IL-17–secreting phenotype, has inhibitory effects on IL-9 production, we hypothesized that reducing circulating IL-23 by treatment with anti-IL-23 antibodies would reduce the establishment and development of parasitic intestinal nematodes. In this study, we show that animals treated with anti-IL-23 monoclonal antibodies showed a drastic reduction in the number of mouse pinworms (Aspiculuris tetraptera) recovered from the intestine (p < 0.001) at 23 days post-infection compared to the untreated animals.…