Although the pathological and toxic effects of the mycotoxin FB1 are well established, there is very little known about its effects on the immune system. Therefore, to investigate the effects of FB1 on the immune function, in our research we used the macrophagic cell line, J774A.1. First we carried out cytotoxicity studies for an initial screening and for testing incubation times and suitable concentrations in order to better observe FB1 effects on the plasma membrane. Considering the clear relationship between oxidative damage, the structural order of plasma membrane lipids, the macrophagic membrane’s ability to internalise proteins, and the physiological immunocompetent role of these cells, we evaluated the mycotoxin effects on: 1) the structural organisation of the plasma membrane through a study on membrane fluidity, 2) membrane related functions such as the endocytic activity, 3) the production of malondialdehyde (MDA), one of the secondary products of lipid peroxidation. We carried out the following experiments on macrophage membranes treating the cells for 24h at concentrations 1-5-10µM of FB1. We observed that a 24h pre-treatment with FB1 10µM increased fluid phase endocytosis measured by HRP internalization. This increase was time and concentration dependent and significative after 120min of incubation with the enzyme (Fig.2, 3). FB1 10µM reduced (p<0.01) the interferon- (100U/ml) inhibiting effect on endocytosis (Fig.4). Moreover FB1 reduced, concentration dependently, microviscosity increasing membrane fluidity (p<0.01 at FB1 10µM). A 24h treatment of J774A.1 with FB1 generated a significant increase in the amount of MDA at all the concentrations tested (p<0.05 at FB1 1µM and p<0.01 at FB1 5 and 10µM). Our results on macrophage membrane are consistent with those of previous papers indicating the multiple effects of the interactions of the fumonisins with the lipid bilayers. The disruption of membrane structure, the enhancement of membrane endocytosis, and the increase in membrane permeability caused by FB1 provide additional insights into potential mechanisms by which the fumonisins might enhance oxidative stress and cellular damage in immune cells, inducing the well known immunodepressive effect of these mycotoxins. The endocytosis modulation by mycotoxin could be due to the modification of membrane architecture according to the results on membrane fluidity. The mycotoxin effects could change the cell response to external stimuli, modifying the binding of proteins or enzymes involved in the different pathways of transduction signalling. In conclusion, the effects of FB1 on macrophages and the mechanisms by which the fumonisins affect the structure and the functions of these immune cell membranes may contribute to the pathogenesis of the diseases caused by this mycotoxin. Further investigation are necessary to clarify FB1 toxicity, apoptotic mechanisms and changes in physical membrane state.

Effect of fumonisin B1 mycotoxin on J774A.1 macrophagic cell membrane / Ferrante, MARIA CARMELA; Meli, Rosaria; MATTACE RASO, Giuseppina; Di Carlo, G.; Lucisano, A.. - In: TOXICOLOGY LETTERS. - ISSN 0378-4274. - STAMPA. - 1:(2000), pp. 44-44. [10.1016/S0378-4274(00)80001-6]

Effect of fumonisin B1 mycotoxin on J774A.1 macrophagic cell membrane

FERRANTE, MARIA CARMELA;MELI, ROSARIA;MATTACE RASO, GIUSEPPINA;
2000

Abstract

Although the pathological and toxic effects of the mycotoxin FB1 are well established, there is very little known about its effects on the immune system. Therefore, to investigate the effects of FB1 on the immune function, in our research we used the macrophagic cell line, J774A.1. First we carried out cytotoxicity studies for an initial screening and for testing incubation times and suitable concentrations in order to better observe FB1 effects on the plasma membrane. Considering the clear relationship between oxidative damage, the structural order of plasma membrane lipids, the macrophagic membrane’s ability to internalise proteins, and the physiological immunocompetent role of these cells, we evaluated the mycotoxin effects on: 1) the structural organisation of the plasma membrane through a study on membrane fluidity, 2) membrane related functions such as the endocytic activity, 3) the production of malondialdehyde (MDA), one of the secondary products of lipid peroxidation. We carried out the following experiments on macrophage membranes treating the cells for 24h at concentrations 1-5-10µM of FB1. We observed that a 24h pre-treatment with FB1 10µM increased fluid phase endocytosis measured by HRP internalization. This increase was time and concentration dependent and significative after 120min of incubation with the enzyme (Fig.2, 3). FB1 10µM reduced (p<0.01) the interferon- (100U/ml) inhibiting effect on endocytosis (Fig.4). Moreover FB1 reduced, concentration dependently, microviscosity increasing membrane fluidity (p<0.01 at FB1 10µM). A 24h treatment of J774A.1 with FB1 generated a significant increase in the amount of MDA at all the concentrations tested (p<0.05 at FB1 1µM and p<0.01 at FB1 5 and 10µM). Our results on macrophage membrane are consistent with those of previous papers indicating the multiple effects of the interactions of the fumonisins with the lipid bilayers. The disruption of membrane structure, the enhancement of membrane endocytosis, and the increase in membrane permeability caused by FB1 provide additional insights into potential mechanisms by which the fumonisins might enhance oxidative stress and cellular damage in immune cells, inducing the well known immunodepressive effect of these mycotoxins. The endocytosis modulation by mycotoxin could be due to the modification of membrane architecture according to the results on membrane fluidity. The mycotoxin effects could change the cell response to external stimuli, modifying the binding of proteins or enzymes involved in the different pathways of transduction signalling. In conclusion, the effects of FB1 on macrophages and the mechanisms by which the fumonisins affect the structure and the functions of these immune cell membranes may contribute to the pathogenesis of the diseases caused by this mycotoxin. Further investigation are necessary to clarify FB1 toxicity, apoptotic mechanisms and changes in physical membrane state.
2000
Effect of fumonisin B1 mycotoxin on J774A.1 macrophagic cell membrane / Ferrante, MARIA CARMELA; Meli, Rosaria; MATTACE RASO, Giuseppina; Di Carlo, G.; Lucisano, A.. - In: TOXICOLOGY LETTERS. - ISSN 0378-4274. - STAMPA. - 1:(2000), pp. 44-44. [10.1016/S0378-4274(00)80001-6]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/490499
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