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Dive into the research topics where Mariela Bollati-Fogolín is active.

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Featured researches published by Mariela Bollati-Fogolín.


European Journal of Immunology | 2006

Interleukin-10 derived from macrophages and/or neutrophils regulates the inflammatory response to LPS but not the response to CpG DNA.

Lisa Siewe; Mariela Bollati-Fogolín; Claudia Wickenhauser; Thomas Krieg; Werner Müller; Axel Roers

Interleukin‐10 (IL‐10) is an important regulator of immune responses secreted by different cell types. We have previously shown that mice with selective inactivation of the IL‐10 gene in T cells suffer from deregulated T cell responses similar to those observed in IL‐10–/– animals. Unlike IL‐10–/– mice, however, T cell‐specific mutants do not mount an enhanced innate immune response to LPS, which must, therefore, be subject to control by IL‐10 from non‐T cells. Herein we show that subcutaneous injection of LPS, which causes moderate local inflammation in WT and T cell‐specific IL‐10 mutant mice, results in augmented inflammatory infiltration and extensive tissue necrosis in mice with deficiency for IL‐10 in macrophages and neutrophils. Correspondingly, we observed an enhanced sensitivity of the macrophage/neutrophil‐specific IL‐10 mutants to systemic LPS exposure when compared with WT animals. In contrast, the inflammatory response of these mutants to CpG oligodeoxynucleotides was not different from that of WT mice. While IL‐10–/– mice developed massive inflammation, necrosis and increased serum cytokine levels after subcutaneous CpG injection, only moderate responses were observed in macrophage/neutrophil‐specific IL‐10 mutant and WT mice. These results show that different innate immune responses can be subject to control by IL‐10 from different cellular sources.


Biotechnology Progress | 2008

Temperature reduction in cultures of hGM-CSF-expressing CHO cells: effect on productivity and product quality.

Mariela Bollati-Fogolín; Guillermina Forno; Manfred Nimtz; Harald S. Conradt; Marina Etcheverrigaray; Ricardo Kratje

We have demonstrated that temperature reduction from 37 to 33 °C in the culture of a CHO cell line producing recombinant human granulocyte macrophage colony stimulating factor (CHO‐K1‐hGM‐CSF) leads to a reduced growth rate, increased cell viability, improved cellular productivity, and decreased cell metabolism. In the present study, CHO‐K1‐hGM‐CSF cells were cultured in a biphasic mode: first, a 37 °C growth phase for achieving a high cell number, followed by a production phase where the culture temperature was shifted to 33 °C. The maximum cell density was not affected after temperature reduction while cell viability remained above 80% for a further 3.7 days in the culture kept at the lower temperature, when compared to the control culture maintained at 37 °C. Furthermore, the total rhGM‐CSF production increased 6 times in the culture shifted to 33 °C. Because the quality and hence the in vivo efficacy of a recombinant protein might be affected by numerous factors, we have analyzed the N‐ and O‐glycosylation of the protein produced under both cell culture conditions using high‐pH anion‐exchange chromatography and complementary mass spectrometry techniques. The product quality data obtained from the purified protein preparations indicated that decreasing temperature had no significant effect on the rhGM‐CSF glycosylation profiles, including the degree of terminal sialylation. Moreover, both preparations exhibited the same specific in vitro biological activity. These results revealed that the employed strategy had a positive effect on the cell specific productivity of CHO‐K1‐hGM‐CSF cells without affecting product quality, representing a novel procedure for the rhGM‐CSF production process.


PLOS ONE | 2012

Anti-Inflammatory Lactobacillus rhamnosus CNCM I-3690 Strain Protects against Oxidative Stress and Increases Lifespan in Caenorhabditis elegans

Gianfranco Grompone; Patricia Martorell; Silvia Llopis; Nuria González; Salvador Genovés; A. P. Mulet; Tamara Fernández-Calero; Inés Tiscornia; Mariela Bollati-Fogolín; Isabelle Chambaud; Benoît Foligné; Agustín Montserrat; Daniel Ramón

Numerous studies have shown that resistance to oxidative stress is crucial to stay healthy and to reduce the adverse effects of aging. Accordingly, nutritional interventions using antioxidant food-grade compounds or food products are currently an interesting option to help improve health and quality of life in the elderly. Live lactic acid bacteria (LAB) administered in food, such as probiotics, may be good antioxidant candidates. Nevertheless, information about LAB-induced oxidative stress protection is scarce. To identify and characterize new potential antioxidant probiotic strains, we have developed a new functional screening method using the nematode Caenorhabditis elegans as host. C. elegans were fed on different LAB strains (78 in total) and nematode viability was assessed after oxidative stress (3 mM and 5 mM H2O2). One strain, identified as Lactobacillus rhamnosus CNCM I-3690, protected worms by increasing their viability by 30% and, also, increased average worm lifespan by 20%. Moreover, transcriptomic analysis of C. elegans fed with this strain showed that increased lifespan is correlated with differential expression of the DAF-16/insulin-like pathway, which is highly conserved in humans. This strain also had a clear anti-inflammatory profile when co-cultured with HT-29 cells, stimulated by pro-inflammatory cytokines, and co-culture systems with HT-29 cells and DC in the presence of LPS. Finally, this Lactobacillus strain reduced inflammation in a murine model of colitis. This work suggests that C. elegans is a fast, predictive and convenient screening tool to identify new potential antioxidant probiotic strains for subsequent use in humans.


Dalton Transactions | 2013

Antitumor properties of a vanadyl(IV) complex with the flavonoid chrysin [VO(chrysin)2EtOH]2 in a human osteosarcoma model: the role of oxidative stress and apoptosis.

Ignacio E. León; A.L. Di Virgilio; V. Porro; Cecilia I. Muglia; L. G. Naso; Patricia A.M. Williams; Mariela Bollati-Fogolín; Susana B. Etcheverry

Flavonoids, a polyphenolic compound family, and the vanadium compounds have interesting biological, pharmacological, and medicinal properties. We report herein the antitumor actions of the complex [VO(chrysin)2EtOH]2 (VOchrys) on the MG-63 human osteosarcoma cell line. Oxovanadium(IV), chrysin and VOchrys caused a concentration-dependent inhibition of cell viability. The complex was the strongest antiproliferative agent (p < 0.05). Cytotoxicity and genotoxicity studies also showed a concentration effect. Reactive oxygen species (ROS) and the alterations in the GSH/GSSG ratio underlie the main mechanisms of action of VOchrys. Additions of ROS scavengers (vitamin C plus vitamin E) or GSH to the viability experiments demonstrated beneficial effects (p < 0.01). Besides, the complex triggered apoptosis, disruption of the mitochondria membrane potential (MMP), increased levels of caspase 3 and DNA fragmentation measured by the sub-G1 peak in cell cycle arrest experiments (p < 0.01). Collectively, VOchrys is a cell death modulator and a promissory complex to be used in cancer treatments.


Inflammatory Bowel Diseases | 2011

Commensal gut flora reduces susceptibility to experimentally induced colitis via T-cell-derived interleukin-10.

Marina C. Pils; André Bleich; Immo Prinz; Nicolas Fasnacht; Mariela Bollati-Fogolín; Angela Schippers; Björn Rozell; Werner Müller

Background: Regulatory cytokines are well known to modify experimental colitis in mice. The aim of this study was to elucidate the effect of interleukin (IL)‐10 derived from different cellular sources and the effect of commensal gut flora in dextran sulfate sodium (DSS)‐induced colitis in mice. Methods: Wildtype (WT) and IL‐10 deficient (IL‐10−/−) mice either harboring a characterized specific pathogen‐free (SPF) gut flora or germfree were exposed to 2% DSS. Moreover, cell type‐specific IL‐10, IL‐4, and IL‐12 knockout mice and animals combining the T‐cell‐specific IL‐10 knockout with a deficiency in IL‐12 or IL‐4 were exposed to DSS. Results: SPF IL‐10−/− mice showed an increased susceptibility to DSS‐induced colitis compared to WT mice determined by histopathology and proinflammatory cytokine and chemokine responses. Under germfree conditions, both WT and IL‐10−/− mice were highly susceptible to DSS. IL‐10 mRNA was increased upon DSS exposure in WT SPF but not in germfree mice. Mice carrying a specific deletion of IL‐10 in T‐cells exhibited a tendency towards an enhanced susceptibility to DSS. The lack of T‐cell‐derived IL‐10 in combination with the lack of IL‐4 increased the susceptibility to DSS colitis, as did the lack of IL‐12 alone. Conclusions: IL‐10 is a crucial factor inhibiting the innate proinflammatory immune response induced by DSS. Intestinal bacteria are necessary for the induction of protective IL‐10, which is mainly T‐cell‐derived. T‐cell‐derived IL‐10 can only mediate its protective effect in a Th1‐dominated milieu. If the balance is shifted towards a Th2 response, IL‐10 is not protective. (Inflamm Bowel Dis 2011;)


Bioorganic & Medicinal Chemistry | 2012

Discovery of new orally effective analgesic and anti-inflammatory hybrid furoxanyl N-acylhydrazone derivatives

Paola Hernández; Mauricio Cabrera; María Laura Lavaggi; Laura Celano; Inés Tiscornia; Thiago Costa; Leonor Thomson; Mariela Bollati-Fogolín; Ana Luisa P. Miranda; Lidia M. Lima; Eliezer J. Barreiro; Mercedes González; Hugo Cerecetto

We report the design, the synthesis and the biological evaluation of the analgesic and anti-inflammatory activities of furoxanyl N-acylhydrazones (furoxanyl-NAH) by applying molecular hybridization approach. Hybrid compounds with IL-8-release inhibition capabilities were identified. Among them, furoxanyl-NAH, 17, and benzofuroxanyl-derivative, 24, together with furoxanyl-NAH derivative, 31, without IL-8 inhibition displayed both orally analgesic and anti-inflammatory activities. These hybrid derivatives do not have additional LOX- or COX-inhibition activities. For instance, LOX-inhibition by furoxanyl-NAH derivative, 42, emerged as a structural lead to develop new inhibitors. The lack of mutagenicity of the active derivatives 17, 31, and 42, allow us to propose them as candidates for further clinical studies. These results confirmed the success in the exploitation of hybridization strategy for identification of novel N-acylhydrazones (NAH) with optimized activities.


BMC Cancer | 2010

In vitro and in vivo anticancer properties of a Calcarea carbonica derivative complex (M8) treatment in a murine melanoma model

Fernando Sf Guimarães; Lucas Ferrari de Andrade; Sharon T Martins; Ana Pr Abud; Reginaldo Vieira de Sene; Carla Wanderer; Inés Tiscornia; Mariela Bollati-Fogolín; Dorly de Freitas Buchi; Edvaldo S. Trindade

BackgroundMelanoma is the most aggressive form of skin cancer and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have had only marginal success. Previous studies in mice demonstrated that a high diluted complex derived from Calcarea carbonica (M8) stimulated the tumoricidal response of activated lymphocytes against B16F10 melanoma cells in vitro.MethodsHere we describe the in vitro inhibition of invasion and the in vivo anti-metastatic potential after M8 treatment by inhalation in the B16F10 lung metastasis model.ResultsWe found that M8 has at least two functions, acting as both an inhibitor of cancer cell adhesion and invasion and as a perlecan expression antagonist, which are strongly correlated with several metastatic, angiogenic and invasive factors in melanoma tumors.ConclusionThe findings suggest that this medication is a promising non-toxic therapy candidate by improving the immune response against tumor cells or even induce direct dormancy in malignancies.


Cancer Immunology, Immunotherapy | 2013

Monoclonal antibodies toward different Tn-amino acid backbones display distinct recognition patterns on human cancer cells. Implications for effective immuno-targeting of cancer

Daniel Mazal; Richard Lo-Man; Sylvie Bay; Otto Pritsch; Edith Dériaud; Christelle Ganneau; Andrea Medeiros; Luis Ubillos; Gonzalo Obal; Nora Berois; Mariela Bollati-Fogolín; Claude Leclerc; Eduardo Osinaga

The Tn antigen (GalNAcα-O-Ser/Thr) is a well-established tumor-associated marker which represents a good target for the design of anti-tumor vaccines. Several studies have established that the binding of some anti-Tn antibodies could be affected by the density of Tn determinant or/and by the amino acid residues neighboring O-glycosylation sites. In the present study, using synthetic Tn-based vaccines, we have generated a panel of anti-Tn monoclonal antibodies. Analysis of their binding to various synthetic glycopeptides, modifying the amino acid carrier of the GalNAc(*) (Ser* vs Thr*), showed subtle differences in their fine specificities. We found that the recognition of these glycopeptides by some of these MAbs was strongly affected by the Tn backbone, such as a S*S*S* specific MAb (15G9) which failed to recognize a S*T*T* or a T*T*T* structure. Different binding patterns of these antibodies were also observed in FACS and Western blot analysis using three human cancer cell lines (MCF-7, LS174T and Jurkat). Importantly, an immunohistochemical analysis of human tumors (72 breast cancer and 44 colon cancer) showed the existence of different recognition profiles among the five antibodies evaluated, demonstrating that the aglyconic part of the Tn structure (Ser vs Thr) plays a key role in the anti-Tn specificity for breast and colon cancer detection. This new structural feature of the Tn antigen could be of important clinical value, notably due to the increasing interest of this antigen in anticancer vaccine design as well as for the development of anti-Tn antibodies for in vivo diagnostic and therapeutic strategies.


Chemico-Biological Interactions | 2014

Polyoxometalates as antitumor agents: Bioactivity of a new polyoxometalate with copper on a human osteosarcoma model

Ignacio E. León; V. Porro; S. Astrada; M.G. Egusquiza; C.I. Cabello; Mariela Bollati-Fogolín; Susana B. Etcheverry

Polyoxometalates (POMs) are early transition metal oxygen anion clusters. They display interesting biological effects mainly related to their antiviral and antitumor properties. On the other hand, copper compounds also show different biological and pharmacological effects in cell culture and in animal models. We report herein for the first time, a detailed study of the mechanisms of action of a copper(II) compound of the group of HPOMs with the formula K7Na3[Cu4(H2O)2(PW9034)2]20H2O (PW9Cu), in a model of human osteosarcoma derived cell line, MG-63. The compound inhibited selectively the viability of the osteosarcoma cells in the range of 25-100μM (p<0.01). Besides, we have clearly shown a more deleterious action of PW9Cu on tumor osteoblasts than in normal cells. Cytotoxicity studies also showed deleterious effects for PW9Cu. The increment of reactive oxygen species (ROS) and the decrease of the GSH/GSSG ratio were involved in the antiproliferative effects of PW9Cu. Moreover, the compound caused cell cycle arrest in G2 phase, triggering apoptosis as determined by flow cytometry. As a whole, these results showed the main mechanisms of the deleterious effects of PW9Cu in the osteosarcoma cell line MG-63, demonstrating that this compound is a promissory agent for cancer treatments.


Journal of Amino Acids | 2013

The Antitumor Peptide CIGB-552 Increases COMMD1 and Inhibits Growth of Human Lung Cancer Cells

Julio Raúl Fernández Massó; Brizaida Oliva Argüelles; Yelaine Tejeda; Soledad Astrada; Hilda Garay; Osvaldo Reyes; Livan Delgado-Roche; Mariela Bollati-Fogolín; Maribel G. Vallespi

We have demonstrated that the peptide L-2 designed from an alanine scanning of the Limulus-derived LALF32-51 region is a potential candidate for the anticancer therapy and its cell-penetrating capacity is an associated useful property. By the modification in the primary structure of L-2, a second-generation peptide (CIGB-552) was developed. However, the molecular mechanism underlying its cytotoxic activity remains partially unknown. In this study, it was shown that CIGB-552 increases the levels of COMMD1, a protein involved in copper homeostasis, sodium transport, and the NF-κB signaling pathway. We found that CIGB-552 induces ubiquitination of RelA and inhibits the antiapoptotic activity regulated by NF-κB, whereas the knockdown of COMMD1 blocks this effect. We also found that CIGB-552 decreases the antioxidant capacity and induces the peroxidation of proteins and lipids in the tumor cells. Altogether, this study provides new insights into the mechanism of action of the peptide CIGB-552, which could be relevant in the design of future anticancer therapies.

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Werner Müller

University of Manchester

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Marina Etcheverrigaray

National Scientific and Technical Research Council

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Ricardo Kratje

National Scientific and Technical Research Council

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Ignacio E. León

National University of La Plata

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Marcos Oggero

National Scientific and Technical Research Council

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Susana B. Etcheverry

National University of La Plata

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Eduardo Osinaga

Institut national de la recherche agronomique

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