Effect Of Bacterial Lipopolysaccharide Research Articles

EFFECTS OF BACTERIAL LIPOPOLYSACCHARIDE AND SHIGA TOXIN ON INDUCED PLURIPOTENT STEM CELL-DERIVED MESENCHYMAL STEM CELLS.

Background : Mesenchymal stem cells (MSCs) can be activated by different bacterial toxins. Lipopolysaccharides and Shiga Toxin (Stx) are the main toxins necessary for hemolytic uremic syndrome development. The main etiological event in this disease is endothelial damage that causes glomerular destruction. Considering the repairing properties of MSC, we aimed to study the response of MSC derived from induced pluripotent stem cells (iPSC-MSC) to LPS and/or Stx and its effect on the restoration of injured endothelial cells. Methods : iPSC-MSC were treated with LPS and or/Stx for 24 h and secretion of cytokines, adhesion, and migration were measured in response to these toxins. In addition, conditioned media from treated iPSC-MSC were collected and used for proteomics analysis and evaluation of endothelial cell healing and tubulogenesis using human microvascular endothelial cells 1 as a source of endothelial cells. Results : The results obtained showed that LPS induced a proinflammatory profile on iPSC-MSC, whereas Stx effects were less evident, even though cells expressed the Gb 3 receptor. Moreover, LPS induced on iPSC-MSC an increment in migration and adhesion to a gelatin substrate. Addition of conditioned media of iPSC-MSC treated with LPS + Stx, decreased the capacity of human microvascular endothelial cells 1 to close a wound, and did not favor tubulogenesis. Proteomic analysis of iPSC-MSC treated with LPS and/or Stx revealed specific protein secretion patterns that support the functional results described. Conclusions : iPSC-MSC activated by LPS acquired a proinflammatory profile that induces migration and adhesion to extracellular matrix proteins but the addition of Stx did not activate any repair program to ameliorate endothelial damage, indicating that the use of iPSC-MSC to regenerate endothelial injury caused by LPS and/or Stx in hemolytic uremic syndrome could not be the best option to consider to regenerate a tissue injury.

The Effects of Bacterial Lipopolysaccharide (LPS) on Turkey Poults: Assessment of Biochemical Parameters and Histopathological Changes.

A lipopolysaccharide (LPS) is a large molecule and an outer membrane glycolipid found in Gram-negative bacteria, including Escherichia coli (E. coli). These molecules (LPS) target acute inflammatory responses and significant physiological changes. Importantly, E. coli is considered one of the most important bacterial causes of avian colibacillosis that affect domestic turkey industry. However, little information is available about the potential influence of LPS on the biochemical parameters and histopathological changes in turkey poults. Therefore, this study aimed to evaluate the influence of bacterial lipopolysaccharide (LPS) molecules on serum biomarkers and histopathological changes in turkey poults. The birds were randomly divided into five groups, as follows: group I did not receive any inoculation; group II was inoculated with sterile saline; and groups III, IV, and V were inoculated intraperitoneally with LPS at 0.01, 0.1, and 1 mg/kg of body weight (BW), respectively. The biochemical parameters and the histopathology of different organs were examined in all birds one day post-inoculation. Our results revealed hypolipidemia, hypoglycemia, a significant decrease in uric acid, and a significant increase in serum activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and creatine kinase (CK), as well as cardiac troponin T concentrations in treated groups. Moreover, there was a significant increase in α1-, β-, and γ-globulin concentrations and a decrease in albumin and α2-globulin concentrations in group V. However, a significant increase in α2- and γ-globulin levels and a decrease in albumin levels were detected in groups III and IV. In addition, significant decreases in the albumin/globulin ratio were recorded in all LPS-treated groups. Hepatocellular and cardiac muscle necrosis, slight renal changes, and massive pulmonary inflammatory reactions were recorded. This study provides valuable information about serum biomarkers, protein fractions, and histopathological changes in turkey poults treated with LPS for further investigations of pathophysiological mechanisms in avian medicine along with biomedical research.

An in vitro Study of the Effect of Bacterial Lipopolysaccharide on Transcription Levels of SLC Family Transporter Genes in Microglia

An in vitro Study of the Effect of Bacterial Lipopolysaccharide on Transcription Levels of SLC Family Transporter Genes in Microglia

Effects of bacterial lipopolysaccharides on platelet function: inhibition of weak platelet activation

Platelets are anucleate blood cells with reported roles in hemostasis and immune responses, which possess a functional receptor for bacterial lipopolysaccharides (LPSs), the well-known inducers of inflammation. However, LPSs effects on platelets are contradictory. Here we aim to investigate mechanisms of platelet functioning in the presence of LPS and to find the cause of the discrepancy in the previously published data. Cell activity was analyzed by flow cytometry, western blotting, and aggregometry. Thrombus growth was assessed by fluorescent microscopy. LPS' activity was checked by their capability to induce PMN activation. However, LPSs did not substantially affect either thrombus growth in flow chambers, irreversible platelet aggregation, or platelet responses to strong activation. Platelet aggregation in response to 1 μM of ADP was significantly inhibited by LPSs. Flow cytometry analysis revealed that platelet activation responses to weak stimulation were also diminished by LPSs, while VASP phosphorylation was weakly increased. Additionally, LPSs were capable of inhibition of ADP-induced P2-receptor desensitization. Incubation of platelets with a pan-PDE inhibitor IBMX significantly enhanced the LPSs-induced platelet inhibition, implying cAMP/cGMP dependent mechanism. The discrepancy in the previously published data could be explained by LPS-induced weak inhibition of platelet activation and the prevention of platelet desensitization.

Mitochondrial-Targeted Antioxidant MitoQ Prevents E. coli Lipopolysaccharide-Induced Accumulation of Triacylglycerol and Lipid Droplets Biogenesis in Epithelial Cells.

The effect of bacterial lipopolysaccharide (LPS) on eukaryotic cell could be accompanied by a significant metabolic shift that includes accumulation of triacylglycerol (TAG) in lipid droplets (LD), ubiquitous organelles associated with fatty acid storage, energy regulation and demonstrated tight spatial and functional connections with mitochondria. The impairment of mitochondrial activity under pathological stimuli has been shown to provoke TAG storage and LD biogenesis. However the potential mechanisms that link mitochondrial disturbances and TAG accumulation are not completely understood. We hypothesize that mitochondrial ROS (mROS) may play a role of a trigger leading to subsequent accumulation of intracellular TAG and LD in response to a bacterial stimulus. Using isolated epithelial cells from the frog urinary bladder, we showed that LPS decreased fatty acids oxidation, enhanced TAG deposition, and promoted LD formation. LPS treatment did not affect the mitochondrial membrane potential but increased cellular ROS production and led to impairment of mitochondrial function as revealed by decreased ATP production and a reduced maximal oxygen consumption rate (OCR) and OCR directed at ATP turnover. The mitochondrial-targeted antioxidant MitoQ at a dose of 25 nM did not prevent LPS-induced alterations in cellular respiration, but, in contrast to nonmitochondrial antioxidant α-tocopherol, reduced the effect of LPS on the generation of ROS, restored the LPS-induced decline of fatty acids oxidation, and prevented accumulation of TAG and LD biogenesis. The data obtained indicate the key signaling role of mROS in the lipid metabolic shift that occurs under the impact of a bacterial pathogen in epithelial cells.

Lipopolysaccharide Potentiates PD-1 Targeted Therapies During Chronic Viral Infection

Programmed cell death-1 (PD-1) targeted therapies improve exhausted T cell responses during chronic infections and cancers. However, the efficacy of PD-1 blockade as a treatment to revert CD8 T cell exhaustion declines as the chronic infection progresses. Moreover, the majority of tumors do not respond to PD-1 blockade, highlighting an important clinical limitation. Recent reports have demonstrated an association between particular microbiota and the clinical efficacy of PD-1 targeted therapies, suggesting that certain bacterial components may influence the outcome of these therapies. In this study, we interrogated synergistic effects of bacterial lipopolysaccharide (LPS), a main component of Gram-negative bacteria and a strong inducer of TLR4 signaling. Using the model of chronic lymphocytic choriomeningitis virus (LCMV) infection in mice, we show that transient TLR4 stimulation with a low dose of LPS results in unprecedented potentiation of PD-1 targeted therapies via a dendritic cell intrinsic mechanism dependent on B7/CD28 costimulation. This profound synergy between PD-1 blockade and LPS was also observed in a model of advanced immune exhaustion that does not normally respond to PD-1 blockade. Taken together, our data demonstrate a potent synergy between LPS and PD-1 blockade at rejuvenating exhausted CD8 T cells during chronic infection, warranting the pre-clinical evaluation of TLR4 agonists to improve PD-1 targeted therapies.

Effect of bacterial lipopolysaccharides on morphogenetic activity in wheat somatic calluses.

We evaluated the effect of lipopolysaccharides from the plant-growth-promoting associative bacterium Azospirillum brasilense Sp245 and from the enteric bacterium Escherichia coli K12 on the morphogenic potential of in vitro-growing somatic calluses of soft spring wheat (Triticum aestivum L. cv. Saratovskaya 29). A genetic model was used that included two near-isogenic lines of T. aestivum L. cv. Saratovskaya 29 with different embryogenic capacities; one of these lines carries the Rht-B1 dwarfing gene, whereas the other lacks it. When added to the nutrient medium, the lipopolysaccharide of A. brasilense Sp245 promoted the formation of calluses with meristematic centers and stimulated the regeneration ability of the cultured tissues in both lines. By contrast, the lipopolysaccharide of the enteric bacterium E. coli K12 barely affected the morphogenetic activity of callus cells and the yield of morphogenic calluses and regenerated plants. These findings indicate that the lipopolysaccharide of the plant-growth-promoting associative bacterium A. brasilense Sp245 specifically enhances the morphogenetic activity of wheat somatic tissues, which increases the efficacy of culturing of genotypes with a relatively low morphogenic potential. The results of the study may contribute to the improvement of the efficacy of plant cell selection and gene engineering and to a better understanding of the mechanisms responsible for plant recognition of lipopolysaccharides of associative bacteria.

Effects of bacterial lipopolysaccharide on serum testosterone level and sperm vitality in mature rats

In the last decades, the light had been shed on the importance of malereproduction and how to protect it from disease conditions andinflammation which may cause infertility. Accordingly, the mechanismunderlying inflammation-mediated infertility must be well clarified. In thepresent study, an experimental model of acute inflammation in mature malealbino rats was established by intraperitoneal (ip) injection of a single doseof lipopolysaccharides (LPS). Consequently, basic reproductive parameterswere estimated after LPS administration. Blood samples were collected andassayed for serum testosterone levels. Semen was also analyzed for livesperm percent. Testes were removed for histopathological evaluation. Thefindings revealed that testosterone level in LPS-treated rats decreasedsignificantly (P<0.05) compared to control rats at 6 and 12 hrs afterinjection. Meanwhile, serum testosterone recovered 72 hrs after injection.Moreover, live sperm percent decreased drastically in LPS-treated rats(P<0.001) compared with control rats at 6 and 12 hrs after LPS injection.Adverse effects of LPS on sperm vitality at 72 hrs after LPS injection werealso found. Microscopic examination revealed that degenerative changeswere observed in LPS-treated rats at 6 and 12 hrs. Most of histopathologicalfindings returned to normal structure in LPS-treated rats at 72 hrs.

Effect of bacterial lipopolysaccharide in primary cultures of human gingival fibroblasts

Summary: Introduction: different factors participate in the pathogenesis ofperiodontal diseases. One factor is the interaction between the fibroblasts and derived productsfrom the microorganisms found in the periodontal environment. Objective: In this work, cultures ofhuman gingival fibroblasts from a healthy donor were used to characterize the in vitro responses tobacterial lipopolysaccharide. Methods: the proliferative response was evaluated using cell count andexpression of CD14 was assessed by flow cytometry. Results: after 24 hours of culture an increase inthe cell number was detected in cultures treated with 1.0 mg/mL LPS, but these differences were notstatistically significant. Human gingival fibroblasts express CD14, but its expression decreases incells cultivated after a short period of time. Nevertheless, lipopolysaccharide helps to recover theexpression of CD14 in fibroblast after 24 hours of culture. Conclusion: preliminary result suggeststhat expression of CD14 on gingival fibroblasts could be modulated by this bacterial derived toxin.The primary culture of human gingival fibroblasts allows the establishment of an in vitro model toevaluate different processes in development of the periodontal diseases. Key words: Gingivalfibroblasts. Lipopolysaccharide. Periodontal disease.

Gut microbiota and obesity: Pathogenetic relationships and ways to normalize the intestinal microflora

The review demonstrates mechanisms in the relationship of obesity to gut microbiota, as well as possible therapeutic measures to normalize the intestinal microflora. There is evidence that the latter makes a great contribution to the pathogenesis of obesity and related diseases. Investigations have shown the role of the nature of consumed foods (fatty foods) in reducing the amount of bifidobacteria and lactobacilli, as well as the effects of bacterial lipopolysaccharides and metabolites from the intestinal microflora (trimethylamine-N-oxide, bile acids, etc.). The use of prebiotics, probiotics and ursodeoxycholic acid preparations and fecal transplantation are promising in correcting the microflora and in providing their positive effect on metabolic disturbances. Certain probiotic strains are effective in treating dyslipidemia, diabetes mellitus, obesity, and metabolic syndrome. Gut microbiota is impaired in obesity and contributes to the development of cardiovascular diseases. The control of the gut microbiota and the use of drugs altering the composition of the microflora may become a novel approach to reducing the risk of cardiovascular diseases.

Overnutrition Determines LPS Regulation of Mycotoxin Induced Neurotoxicity in Neurodegenerative Diseases.

Chronic neurodegenerative diseases are now associated with obesity and diabetes and linked to the developing and developed world. Interests in healthy diets have escalated that may prevent neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. The global metabolic syndrome involves lipoprotein abnormalities and insulin resistance and is the major disorder for induction of neurological disease. The effects of bacterial lipopolysaccharides (LPS) on dyslipidemia and NAFLD indicate that the clearance and metabolism of fungal mycotoxins are linked to hypercholesterolemia and amyloid beta oligomers. LPS and mycotoxins are associated with membrane lipid disturbances with effects on cholesterol interacting proteins, lipoprotein metabolism, and membrane apo E/amyloid beta interactions relevant to hypercholesterolemia with close connections to neurological diseases. The influence of diet on mycotoxin metabolism has accelerated with the close association between mycotoxin contamination from agricultural products such as apple juice, grains, alcohol, and coffee. Cholesterol efflux in lipoproteins and membrane cholesterol are determined by LPS with involvement of mycotoxin on amyloid beta metabolism. Nutritional interventions such as diets low in fat/carbohydrate/cholesterol have become of interest with relevance to low absorption of lipophilic LPS and mycotoxin into lipoproteins with rapid metabolism of mycotoxin to the liver with the prevention of neurodegeneration.

Bacterial lipopolysaccharide activates CD57-negative human NK cells.

NK cells play an important regulatory role in sepsis by induction and augmentation of proinflammatory reactions in early stages of the septic process and by suppression of immune response in later stages of inflammation. The present work was aimed at the effect of bacterial lipopolysaccharide (LPS), the main pathogenic factor of sepsis development, on human NK cells ex vivo. We show that LPS activates immature CD57-negative NK cells, which typically constitute less than half of the normal NK cell population in human peripheral blood. Under conditions of NK cell stimulation with IL-2, addition of LPS provokes an increase in IFN-γ production. However, LPS both increased and inhibited NK cell cytotoxic activity. It is important to note that the activation of NK cells on LPS addition was observed in the absence of TLR4 on the NK cell surface. These results confirm our previous data arguing for a direct interaction of LPS with NK cells and evidence an atypical mechanism of LPS-induced NK cell activation without the involvement of surface TLR4.

MTOR inhibition modulates epileptogenesis, seizures and depressive behavior in a genetic rat model of absence epilepsy

Several signaling pathways are believed to be involved in the epileptogenic process that triggers the subsequent changes in the brain causing epilepsy. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that in the brain, regulates several important physiological functions such as neuronal development and synaptic plasticity, and also seems to be involved in many pathologies, including epilepsy and psychiatric disorders. Previous work in animal models of both genetic and acquired generalized convulsive epilepsies, has suggested that modulators of the mTOR signaling pathway may have beneficial neuroprotective and antiepileptogenic effects. Here, we investigated for the first time, the effect of some treatment schedules (i.e. early chronic, sub-chronic and acute) with the specific mTOR inhibitor rapamycin, on the development of absence seizures and seizure parameters as well as depressive-like behavior in WAG/Rij rats, a genetic model of absence epilepsy, epileptogenesis and mild-depression comorbidity. In addition, we studied the possible interaction between rapamycin treatment and the effects of bacterial lipopolysaccharide (LPS) endotoxin administration, which is known to aggravate absence seizures through generation of increased neuroinflammatory responses. We found that rapamycin (early chronic treatment for 17 weeks, starting at P45) exhibited clear antiepileptogenic properties also in this animal epilepsy model; however, this effect was accompanied by unexpected prodepressant effects. Both acute and sub-chronic (7 day) treatments also had anti-absence properties, but the sub-chronic treatment produced contrasting antidepressant properties in the WAG/Rij rats that were not seen in control Wistar rats. The rapamycin/LPS co-administration studies showed that rapamycin blocked or prevented the LPS-dependent increase in absence seizures, suggesting an anti-inflammatory-like protective action. In conclusion, we have demonstrated a novel antiepileptogenic effect of rapamycin in a well-established animal model of absence epilepsy, and we suggest that this effect may be mediated by the inhibition of inflammatory processes that are developed in the brain of these specific animals during epileptogenesis and during seizures. Our experiments here suggest new insights into this intriguing field, which deserves to be further explored.This article is part of the Special Issue entitled ‘New Targets and Approaches to the Treatment of Epilepsy’.

Lipopolysaccharide induces mitochondrial dysfunction in rat cardiac microvascular endothelial cells

Endothelial injury and dysfunction are key patho-physiological processes in sepsis. The aim of the study was to evaluatethe effects of bacterial lipopolysaccharide (LPS) on cellular respiration of rat primary cardiac microvascular endothelial cells (CMEC).

Haemocyte phagocytosis, exocytosis and their signal transduction in white shrimp (&lt;I&gt;Litopenaeus vannamei&lt;/I&gt;) induced by lipopolysaccharide and dopamine

Effects of bacterial lipopolysaccharide ( LPS) and dopamine ( DA) on phagocytic activity, exocytosis and signal transduction of haemocytes in white shrimp (Litopenaeus vannamei) were studied. The haemocytes treated with LPS (1 - 10 mg/L) and dopamine (1 - 10 μmol/L) in vitro showed conspicuous dose-dependent decrease in cell count,and increase in extracellular phenoloxidase (PO) activity. Phagocytic activity of haemocytes was promoted by LPS and inhibited by dopamine. Meanwhile,the addition of chelerythrine (a PKA inhibitor) and genistein (a TPK inhibitor) to haemocytes can inhibit phagocytosis and exocytosis induced by LPS,and the inhibitory efficiencies on phagocytosis and exocytosis respectively were: genistein chelerythrine,chelerythrine genistein. Dopamine-induced cell phagocytosis was strenghtend by H-89 (a PKA inhibitor),its exocytosis was inhibited by chelerythrine and genistein,and the efficiency was chelerythrine genistein,and the two inhibitors had no impact on dopamine-induced phagocytosis.

Effect of Bacterial Lipopolysaccharide on Na+/H+ Exchanger Activity in Dendritic Cells

The function of dendritic cells (DCs), antigen-presenting cells linking innate and adaptive immunity, is stimulated by bacterial lipopolysaccharides (LPS), which trigger the formation of reactive oxygen species (ROS). In macrophages, ROS formation is paralleled by activation of the Na⁺/H⁺ exchanger, a carrier involved in the regulation of cytosolic pH and cell volume. The present study explored whether LPS influence Na⁺/H⁺ exchanger activity in DCs. The DCs were isolated from murine bone marrow, cell volume was estimated from forward scatter in FACS analysis, ROS production from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, apoptosis from annexin V binding, cytosolic pH (pH_i) from 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence and Na⁺/H⁺ exchanger activity from the Na⁺ dependent realkalinization following an ammonium pulse. Exposure of DCs to LPS (1 µg/ml) led to a transient increase of Na⁺/H⁺ exchanger activity. Moreover, LPS increased forward scatter and ROS formation and decreased apoptosis. The NHE1 inhibitor cariporide (10 µM) virtually abrogated Na⁺/H⁺ exchanger activity, inhibited LPS-induced cell swelling, blunted LPS-induced ROS formation and reversed the antiapoptotic effect of LPS. Na⁺/H⁺ exchanger activity was stimulated by oxidative stress and LPS induced stimulation of NHE activity was abolished in presence of ROS chelators (Tempol, Tiron and Vitamin C). In conclusion, LPS treatment transiently upregulates the Na⁺/H⁺ exchanger in DCs, an effect required for the effects of LPS on DC survival, cell volume and ROS formation.

Cataleptogenic effect of bacterial lipopolysaccharide in mice

Cataleptogenic effect of bacterial lipopolysaccharide in mice

Evidence from knockout mice that peptide YY and neuropeptide Y enforce murine locomotion, exploration and ingestive behaviour in a circadian cycle- and gender-dependent manner

Peptide YY (PYY) and neuropeptide Y (NPY) have been proposed to participate in the control of energy homeostasis. Since these activities show circadian variations, we explored the circadian pattern of locomotor, exploratory and ingestive behaviour in male and/or female mice with disrupted genes for PYY (PYY−/−), NPY (NPY−/−) as well as PYY plus NPY (PYY+NPY−/−). The effect of bacterial lipopolysaccharide (LPS, 0.1mg/kg intraperitoneally) on these behaviours was also examined. The animals were housed singly in cages fitted with sensors for water and food intake and two infrared frames for recording ambulation and rearing under a 12h light/dark cycle for 4 days. Locomotor and exploratory behaviour was decreased in female NPY−/− as well as male and female PYY+NPY−/− mice during the photo- and scotophase, and in male PYY−/− mice during the scotophase. Significant decreases in water and food intake were seen in female NPY−/− as well as male and female PYY+NPY−/− mice during the photophase. The effect of LPS to attenuate ingestive behaviour during the light and/or dark phase was most pronounced in PYY−/− and NPY−/− mice. These findings attest to a circadian cycle- and gender-related role of NPY and PYY in the control of behaviours that balance energy intake and energy expenditure. Both peptides stimulate feeding and drinking to balance the energy demand that they generate by enforcing the circadian pattern of locomotion and exploration. In addition, they counteract the anorectic and antidipsogenic effects of immune challenge.

Effect of Bacterial Lipopolysaccharide on Ischemic Damage in the Rat Retina

The purpose of this study was to investigate whether bacterial lipopolysaccharide (LPS) induces ischemic preconditioning in the rat retina, and, if so, whether nitric oxide (NO) is involved in this process. Rats were intravitreously injected with different doses of LPS (0.1, 1, or 5 microg) in one eye and vehicle in the contralateral eye 24 hours before retinal ischemia induced by increasing intraocular pressure to 120 mm Hg for 40 or 60 minutes. Subsequently, 7 or 14 days after ischemia, the rats were subjected to electroretinography and histologic analysis. One group of animals received intraperitoneal injections of NOS inhibitors, N-nitro-L-arginine methyl ester (L-NAME) aminoguanidine or N-(3-(aminomethyl)benzyl)acetamidine (W1400) before the injection of LPS or vehicle. Retinal nitric oxide synthase (NOS) activity was assessed through the conversion of (3)H-L-arginine to (3)H-L-citrulline. One microgram (but not 0.1 or 5 microg) LPS afforded significant morphologic and functional protection in eyes exposed to ischemia-reperfusion injury. The beneficial effect of LPS was reversed by treatment with L-NAME, aminoguanidine, or W1400. LPS (1 and 5 microg, but not 0.1 microg) significantly increased retinal NOS activity. These results indicate that LPS provides retinal protection against ischemia-reperfusion injury in a dose-dependent manner, probably through an inducible NOS-dependent mechanism.

Further preliminary assessment of three human glioma cell lines as models of human astrocytic toxicity in vitro

Three human astroglioma lines U251-MG, U373-MG and CCF-STTG1 have been evaluated further as possible models for astrocytotoxicity (GFAP and IL-6 release). The effects of bacterial lipopolysaccharide, chloroquine diphosphate and acrylamide were studied on GFAP expression and LPS, chloroquine diphosphate, ethanol, trimethyltin chloride (TMTC) and acrylamide were examined on interleukin-6 (IL-6) release in the U373-MG line only. At 4-h LPS elevated GFAP (17.0 ± 5.0% P < 0.05) above control in the U251-MG cell line only. Chloroquine diphosphate over 4 h in the U251-MG line resulted in an increase in GFAP-IR to 20.3 ± 4.2% and 21.1 ± 4.1% above control levels 0.1 μM ( P < 0.05) and 1 μM ( P < 0.05) respectively. CQD was associated with decreases in MTT turnover, particularly after 24 h incubation. With the U373-MG line, LPS (0.5 μg/ml) increased IL-6 expression 640% above control ( P < 0.001), whilst chloroquine diphosphate (100 μM), ethanol (10 mM) and TMTC chloride (1 μM) also increased IL-6. It is possible that batteries of astrocytic human glioma cell lines may be applicable to the sensitive evaluation of toxicants on astrogliotic expression markers such as GFAP and IL-6.