scholarly journals Metabolism of agmatine in macrophages: modulation by lipopolysaccharide and inhibitory cytokines

1998 ◽  
Vol 330 (3) ◽  
pp. 1405-1409 ◽  
Author(s):  
Magdalena SASTRE ◽  
Elena GALEA ◽  
Douglas FEINSTEIN ◽  
J. Donald REIS ◽  
Soundararajan REGUNATHAN

Agmatine is an amine derived from the decarboxylation of arginine by arginine decarboxylase (ADC) and metabolized to putrescine by agmatinase. While prevalent in bacteria and plants, agmatine and its metabolic enzymes have been recently identified in mammalian tissues. In the present study we sought to determine: (a) whether macrophages (cell line RAW 264.7) express ADC and agmatinase, and (b) if the enzymes are regulated by lipopolysaccharide (LPS), and/or by the inhibitory cytokines transforming growth factor-β (TGF-β), interleukin-10 (IL-10) and interleukin-4 (IL-4). LPS induced a dose-dependent stimulation of agmatinase, while it decreased ADC, the effect in both cases being maximum at 20 h. As expected, LPS dose-dependently stimulated the inducible nitric oxide synthase activity (iNOS). A strong correlation was observed between the effects of LPS on the agmatine-related enzymes and iNOS. By contrast, exposure to IL-10 and TGF-β caused a reduction in ADC and agmatinase, whereas IL-4 was ineffective on ADC, but reverted the LPS-induced increase of agmatinase. We conclude that the agmatine pathway may be an alternative metabolic route for arginine in macrophages, suggesting a regulatory role of agmatine during inflammation.

Toxins ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 350
Author(s):  
Kazimierz Obremski ◽  
Wojciech Trybowski ◽  
Paweł Wojtacha ◽  
Magdalena Gajęcka ◽  
Józef Tyburski ◽  
...  

The aim of the present study was to determine the effect of zearalenone (ZEN), administered per os to gilts at doses equivalent to 50%, 100%, and 150% of no-observed-adverse-effect level (NOAEL) values for 14, 28, and 42 days during weaning, on changes in the parameters of the oxidoreductive balance, cytokine secretion, and basal metabolism in ileal Payer’s patches. Immunoenzymatic ELISA tests and biochemical methods were used to measure the concentrations of interleukin 1α, interleukin 1β, interleukin 12/23p40, interleukin 2, interferon γ, interleukin 4, interleukin 6, interleukin 8, tumor necrosis factor α, interleukin 10, transforming growth factor β, malondialdehyde, sulfhydryl groups, fructose, glucose, and proline, as well as the activity of peroxidase, superoxide dismutase and catalase. The study demonstrated that ZEN doses corresponding to 50%, 100%, and 150% of NOAEL values, i.e., 5 µg, 10 µg, and 15 µg ZEN/kg BW, respectively, have proinflammatory properties, exacerbate oxidative stress responses, and disrupt basal metabolism in ileal Payer’s patches in gilts.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Blanca Cárdaba ◽  
David Calzada ◽  
Selene Baos ◽  
Miriam Aguerri ◽  
Joaquín Quiralte ◽  
...  

Sensitization to specific olive pollen-allergens (Ole e 2 and 10) has been correlated with a clinical pattern of asthma. This study analyzes the association between several polymorphims ofTNFA(G-308A,C-857T, andC-1031T),IL10(C-571AandA-1117G), andTGFB(C-509-T) and these sensitizations. These polymorphisms were genotyped by allelic discrimination, in olive pollen-allergic patients (phenotyped for specific Ole e 2 and 10 sensitizations) and healthy controls. Levels of serum-soluble cytokines were correlated with specific genotypes and clinical phenotypes. The results showed that heterozygousTGFB C-509Tgenotype, besides having the lowest sera TGF- levels, was significantly increased in olive pollen-allergic patients compared with controls. According specific sensitizations,CCgenotype ofIL10 C-571Acould be a protective factor for Ole e 2 sensitization and mainly for asthmatic Ole e 2 sensitized patients compared with asthmatic non-Ole e 2 sensitized patients (OR: 0.26,P=0.008). In contrast, heterozygousCAgenotype was increased in Ole e 2 asthmatic subjects compared to asthmatic non-Ole e 2 sensitized patients. Lastly, heterozygousTNFA G-308Agenotype was associated with Ole e 10 sensitization (OR: 2.5,P=0.04). In conclusion, these results suggest a role of TGF-β1 in olive-pollen sensitization and TNF-αand IL-10 genotypes in the asthma induced by specific olive-pollen allergens.


2011 ◽  
Vol 39 (5) ◽  
pp. 1433-1436 ◽  
Author(s):  
Christine Galustian ◽  
Annapurna Vyakarnam ◽  
Oussama Elhage ◽  
Oliver Hickman ◽  
Prokar Dasgupta ◽  
...  

Prostate adenocarcinoma is present in over 80% of men over the age of 80 and is by far the most common cancer of men. Although radical prostatectomy is curative in early disease, the risks of incontinence and impotence can affect the quality of life of patients. Early intervention with localized immunotherapy represents a potential solution as lymphocyte infiltration does occur in prostate cancer lesions, and immunotherapy with dendritic cell vaccines can significantly increase survival in late stage disease. However, lymphocytic infiltrates in the cancerous prostates have an anergic character arising from the suppressive effects of the microenvironment resulting from a conversion of effector cells into regulatory T-cells. Although TGFβ (transforming growth factor β) and IL-10 (interleukin-10) are known to be strong suppressor molecules associated with prostate cancer, they are among many possible suppressive factors. We discuss the possible role of alternative suppressor molecules, including the WAP (whey acidic protein) homologue ps20 that is expressed on prostate stroma and other WAP domain-containing proteins in the immunosuppressive prostate cancer milieu and discuss novel immunotherapeutic strategies to combat this disease.


2019 ◽  
Vol 32 (4) ◽  
pp. 236-239
Author(s):  
Anna Dworzanska ◽  
Malgorzata Strycharz-Dudziak ◽  
Ewa Kliszczewska ◽  
Bartlomiej Drop ◽  
Malgorzata Polz-Dacewicz

Abstract Increasing interest has been focused on the Epstein-Barr Virus (EBV)-associated cancers, including oropharyngeal cancer (OPC) and gastric cancer (GC). Different cytokines, growth factors and proteins take part in oncogenesis. The aim of our study was to generate a comparison of interleukin 10 (IL-10) and transforming growth factor β (TGF-β) levels, as well as latent membrane protein (LMP-1), Epstein-Barr virus capsid antigen (EBVCA), Epstein-Barr virus nuclear antigen (EBNA) and early antigen (EA) frequency in the serum of patients with GC and OPC. The study involved 50 patients with diagnosed GC and 50 patients with OPC. All studied patients were EBV positive. Fresh-frozen tumor tissue fragments were tested using nested PCR assay for EBV DNA detection. Sera from all individuals were investigated using ELISA tests to detect the presence of EBVCA IgG, EBNA IgG, EA IgG, as well as to determine the levels of IL-10 and TGF-β. The obtained results were subjected to statistical analysis. In patients with GC, the levels of TGF-β and IL-10 were significantly higher than in OPC patients. However, the frequency and level of EBVCA, EBNA and EA in patients with OPC and GC were not significantly different. In contrast, TGF-β and IL-10 levels were significantly higher in EBVaGC, as compared to OPC, suggesting their role in gastric carcinogenesis. The differences in frequency of LMP-1 detection in patients with OPC and GC may suggest different mechanism of oncogenesis. Further studies are required to clarify the role of Epstein-Barr virus in cancer development.


1996 ◽  
Vol 91 (4) ◽  
pp. 519-523 ◽  
Author(s):  
Uzi Gafter ◽  
Yona Kalechman ◽  
Benjamin Sredni

1. Blood transfusion confers immune suppression with improved allograft survival. The aim of this study was to evaluate the effect of blood transfusion on the production of T-helper-2 cytokines and transforming growth factor β, which are associated with suppression of allograft rejection. An additional aim was to try to identify which blood cell type is mostly responsible for the blood transfusion effect. Production of interleukin-4, interleukin-10 and transforming growth factor β by peripheral blood mononuclear cells isolated from patients with end-stage renal disease was measured in vitro. These assays were performed before, and 4 h, 4, 7 and 14 days after a single blood transfusion and the transfusion of one unit of leucocyte-free erythrocytes. 2. Blood transfusion stimulated a significant rise in the production of all three cytokines measured. Transfusion of erythrocytes had no effect on the production of interleukin-4 or interleukin-10. 3. It is suggested that blood transfusion enhances the production of interleukin-4, interleukin-10 and transforming growth factor β. These cytokines may inhibit production of T-helper 1 and pro-inflammatory cytokines, deactivate cytotoxic cells and thereby suppress allograft rejection. It is further suggested that the leucocyte is the transfused cell type which is mostly associated with induction of this immunosuppressive response.


1998 ◽  
Vol 188 (1) ◽  
pp. 39-48 ◽  
Author(s):  
Fakhereldin M. Omer ◽  
Eleanor M. Riley

We have examined the role of the immunomodulatory cytokine transforming growth factor (TGF)-β in the resolution and pathology of malaria in BALB/c mice. Circulating levels of TGF-β, and production of bioactive TGF-β by splenocytes, were found to be low in lethal infections with Plasmodium berghei. In contrast, resolving infections with P. chabaudi chabaudi or P. yoelii were accompanied by significant TGF-β production. A causal association between the failure to produce TGF-β and the severity of malaria infection was demonstrated by treatment of infected mice with neutralizing antibody to TGF-β, which exacerbated the virulence of P. berghei and transformed a resolving P. chabaudi chabaudi infection into a lethal infection, but had little effect on the course of P. yoelii infection. Parasitemia increased more rapidly in anti–TGF-β–treated mice but this did not seem to be the explanation for the increased pathology of infection as peak parasitemias were unchanged. Treatment of P. berghei–infected mice with recombinant TGF-β (rTGF-β) slowed the rate of parasite proliferation and prolonged their survival from 15 to up to 35 d. rTGF-β treatment was accompanied by a significant decrease in serum tumor necrosis factor α and an increase in interleukin 10. Finally, we present evidence that differences in TGF-β responses in different malaria infections are due to intrinsic differences between species of malaria parasites in their ability to induce production of TGF-β. Thus, TGF-β seems to induce protective immune responses, leading to slower parasite growth, early in infection, and, subsequently, appears to downregulate pathogenic responses late in infection. This duality of effect makes TGF-β a prime candidate for a major immunomodulatory cytokine associated with successful control of malaria infection.


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