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Hermann-josef Thierse - One of the best experts on this subject based on the ideXlab platform.
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proteomic allergen peptide protein interaction assay for the identification of human Skin sensitizers
Toxicology in Vitro, 2013Co-Authors: Lisa Dietz, Sven Kinzebach, Stefanie Ohnesorge, Bastian Franke, Irina Goette, Hermann-josef Thierse, Dieter KoeniggresselAbstract:Modification of proteins by Skin sensitizers is a pivotal step in T cell mediated allergic contact dermatitis (ACD). In this process small reactive chemicals interact covalently or non-covalently with cellular or extracellular Skin self-proteins or self-peptides to become recognized by the human immune system. Aiming to develop a novel non-animal in vitro test system for predicting sensitization potential of small reactive chemicals in human Skin the allergen-peptide/protein interaction assay (APIA) has been developed. By applying modern proteomic technologies together with a target peptide containing all amino acids, the assay permits the profiling of all amino acid specific allergen-peptide interactions. Moreover, potentially crucial allergen-specific Cys-modifications are qualitatively monitored by mass spectrometry and confirmed by a dual peptide approach. Assay conditions chosen mimic the distinct human epidermal reactivity compartments of the Skin surface (pH 5.5), stratum basale (pH 6.8), and typical physiological conditions (pH 7.4). An extreme as well as a moderate human contact sensitizer produced Cys-specific mass shifts, whereas a Skin Irritant did not. Our data indicate that MALDI-MS based and Skin-related in vitro technology platforms - like the APIA - are promising tools in developing alternative non-animal allergen assays. This will assist in chemical classification and next generation risk assessment strategies, including REACH and experimental immunotoxicology.
Ian Kimber - One of the best experts on this subject based on the ideXlab platform.
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Skin sensitization induced langerhans cell mobilization variable requirements for tumour necrosis factor α
Immunology, 2015Co-Authors: L H Eaton, Rebecca Jane Dearman, Ian Kimber, Ruth A Roberts, Aleksandra MetrykaAbstract:Upon antigen/allergen recognition, epidermal Langerhans' cells (LC) are mobilized and migrate to the local lymph node where they play a major role in initiating or regulating immune responses. It had been proposed that all chemical allergens induce LC migration via common cytokine signals delivered by TNF-? and IL-1?. Here the dependence of LC migration on TNF-? following treatment of mice with various chemical allergens has been investigated. It was found that under standard conditions the allergens oxazolone, paraphenylene diamine, and trimellitic anhydride, in addition to the Skin Irritant sodium lauryl sulfate, were unable to trigger LC mobilization in the absence of TNF-? signalling. In contrast, two members of the dinitrohalobenezene family (2,4-dinitrochlorobenzene [DNCB] and 2,4-dinitrofluorobenzene [DNFB]) promoted LC migration independently of TNF-R2 (the sole TNF-? receptor expressed by LC) and TNF-? although the presence of IL-1? was still required. However, increasing doses of oxazolone overcame the requirement of TNF-? for LC mobilization, whereas lower doses of DNCB were still able to induce LC migration in a TNF-?-independent manner. These novel findings demonstrate unexpected heterogeneity among chemical allergens and furthermore that LC can be induced to migrate from the epidermis via different mechanisms that are either dependent or independent of TNF-?. Although the exact mechanisms with regard to the signals that activate LC have yet to be elucidated, these differences may translate into functional speciation that will likely impact on the extent and quality of allergic sensitization. This article is protected by copyright. All rights reserved.
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differential regulation of epidermal langerhans cell migration by interleukins il 1α and il 1β during Irritant and allergen induced cutaneous immune responses
Toxicology and Applied Pharmacology, 2002Co-Authors: Marie Cumberbatch, Rebecca Jane Dearman, Richard Groves, Christos Antonopoulos, Ian KimberAbstract:Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-18 are all known to contribute to the regulation of epidermal Langerhans cells (LC) migration and the subsequent accumulation of dendritic cells (DC) in draining lymph nodes following Skin sensitization. However, the cytokine signals that control these responses following Skin irritation have yet to be defined. We demonstrate that IL-1alpha, a cytokine associated with Skin injury and inflammation, is able to stimulate the activation and migration from the epidermis of LC and their subsequent accumulation in Skin-draining lymph nodes. Stimulation of these responses by IL-1alpha required the local availability of TNF-alpha. Using specific neutralizing antibodies, LC migration induced following Skin sensitization with oxazolone (Ox) was found to be dependent upon IL-1beta and independent of a requirement for IL-1alpha. However, the converse was true following stimulation of responses with the nonsensitizing Skin Irritant sodium lauryl sulfate (SLS). Here, the loss of LC from the epidermis and the accumulation of DC in draining lymph nodes required IL-1alpha and not IL-1beta. Despite utilizing different IL-1 isoforms for LC mobilization, the phenotypic characteristics of DC arriving in draining lymph nodes in response to Ox and SLS were similar with respect to the membrane determinants MHC class II, B7-1, B7-2, and intercellular adhesion molecule-1. These data suggest that contact sensitization and Skin irritation employ subtly different cytokine networks in the regulation of LC migration, both involving TNF-alpha but demonstrating differential requirements for IL-1 cytokines. The proposal is that different forms of cutaneous trauma may achieve LC migration through distinct molecular mechanisms.
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langerhans cells require signals from both tumour necrosis factor α and interleukin 1β for migration
Immunology, 1997Co-Authors: Marie Cumberbatch, Rebecca Jane Dearman, Ian KimberAbstract:Tumour necrosis factor α (TNF-α) is considered to play an important role in the initiation of epidermal Langerhans cell (LC) migration during the induction phase of cutaneous immune responses.1 Intradermal injection of mice with homologous recombinant TNF-α stimulates both the migration away from the epidermis of a proportion of LC and the subsequent accumulation in draining lymph nodes of dendritic cells (DC).2,3 Moreover, treatment of mice with a neutralizing anti-TNF-α antibody has been shown to inhibit markedly the increase in lymph node DC associated with exposure to Skin sensitizing chemicals,4,5 ultraviolet B light,6 or the Skin Irritant sodium lauryl sulphate.4
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further evaluation of the local lymph node assay in the final phase of an international collaborative trial
Toxicology, 1996Co-Authors: Scott E Loveless, Rebecca Jane Dearman, E W Scholes, Cindy A Ryan, Robert V. House, J. Hilton, G. Frank Gerberick, Gregory S. Ladics, Ian KimberAbstract:The local lymph node assay (LLNA) is a method used for the prospective identification in mice of chemicals that have the potential to cause Skin sensitization. We report here the results of the second and final phase of an international trial in which the performance of the assay has been evaluated using seven test materials in five independent laboratories. The additional chemicals examined here included compounds which are considered less potent allergens than some of those tested in the first phase of the investigation, and includes hexylcinnamic aldehyde (HCA), a chemical recommended by the Organization for Economic Cooperation and Development (OECD) as a positive control for Skin sensitization studies. In each laboratory all Skin sensitizing chemicals examined (2,4-dinitrochlorobenzene (DNCB), HCA, oxazolone, isoeugenol and eugenol) elicited positive responses of comparable magnitude as judged by the derived lowest concentration of test chemical required to elicit a 3-fold or greater increase in the proliferative activity of draining lymph node cells compared with vehicle-treated controls. We observed that sodium lauryl sulphate, considered to be a non-sensitizing Skin Irritant, also induced a positive response in the assay. Para-aminobenzoic acid (pABA), a nonsensitizing chemical, was negative at all test concentrations in each laboratory. Some laboratories incorporated minor modifications into the standard assay procedure, including the evaluation of lymph nodes pooled from individual mice rather than treatment groups and the use of statistical analyses. The use of statistics did not markedly change the determination of the lowest concentration yielding a positive response. These data confirm that the local lymph node assay is robust and yields equivalent results when performed independently.
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tumour necrosis factor alpha is required for accumulation of dendritic cells in draining lymph nodes and for optimal contact sensitization
Immunology, 1995Co-Authors: Marie Cumberbatch, Ian KimberAbstract:Following Skin sensitization epidermal Langerhans' cells (LC), many of which bear antigen, are stimulated to migrate from the Skin and traffic via afferent lymphatics to lymph nodes draining the site of exposure. It has been proposed previously that tumour necrosis factor-alpha (TNF-alpha), a keratinocyte-derived epidermal cytokine (the expression of which is augmented following cutaneous sensitization), provides one signal for LC migration. In the experiments described here the influence of systemically administered neutralizing anti-TNF-alpha antibody on dendritic cell (DC) accumulation in draining lymph nodes has been investigated. Treatment with anti-TNF-alpha inhibited markedly the frequency of DC in draining nodes measured 18 hr following exposure to the Skin allergens oxazolone and fluorescein isothiocyanate or to the non-sensitizing Skin Irritant sodium lauryl sulphate. Similar treatment with anti-TNF-alpha 2 hr prior to primary exposure to oxazolone impaired significantly the efficiency of Skin sensitization measured 5 days later as a function of challenge-induced increases in ear thickness. The same antibody administered 18 hr following initial exposure to oxazolone was without effect on Skin sensitization. These data confirm the importance of TNF-alpha for the migration of LC from the Skin to draining lymph nodes and demonstrate that this cytokine is required for optimal contact sensitization.
Makoto Hashimoto - One of the best experts on this subject based on the ideXlab platform.
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Isolation and characterization of 1-palmitoyl-2-linoleoyl-sn-glycerol as a hormogonium-inducing factor (HIF) from the coralloid roots of Cycas revoluta (Cycadaceae)
Scientific reports, 2019Co-Authors: Yasuyuki Hashidoko, Hiroaki Nishizuka, Manato Tanaka, Kanako Murata, Yuta Murai, Makoto HashimotoAbstract:Coralloid roots are specialized tissues of cycads (Cycas revoluta) that are involved in symbioses with nitrogen-fixing Nostoc cyanobacteria. We found that a crude methanolic extract of coralloid roots induced differentiation of the filamentous cell aggregates of Nostoc species into motile hormogonia. Hence, the hormogonium-inducing factor (HIF) was chased using bioassay-based isolation, and the active principle was characterized as a mixture of diacylglycerols (DAGs), mainly composed of 1-palmitoyl-2-linoleoyl-sn-glycerol (1), 1-palmitoyl-2-oleoyl-sn-glycerol (2), 1-stearoyl-2-linolenoyl-sn-glycerol (3), and 1-stearoyl-2-linoleoyl-sn-glycerol (4). Enantioselectively synthesised compound 1 showed a clear HIF activity at 1 nmol (0.6 µg) disc−1 for the filamentous cells, whereas synthesised 2-linoleoyl-3-palmitoyl-sn-glycerol (1′) and 1-palmitoyl-2-linoleoyl-rac-glycerol (1/1′) were less active than 1. Conversely, synthesised 1-linoleoyl-2-palmitoyl-rac-glycerol (8/8′) which is an acyl positional isomer of compound 1 was inactive. In addition, neither 1-monoacylglycerols nor phospholipids structurally related to 1 showed HIF-like activities. As DAGs are protein kinase C (PKC) activators, 12-O-tetradecanoylphorbol-13-acetate (12), urushiol C15:3-Δ10,13,16 (13), and a Skin Irritant anacardic acid C15:1-Δ8 (14) were also examined for HIF-like activities toward the Nostoc cells. Neither 12 nor 13 showed HIF-like activities, whereas 14 showed an HIF-like activity at 1 nmol/disc. These findings appear to indicate that some DAGs act as hormogonium-inducing signal molecules for filamentous Nostoc cyanobacteria.
Yasuyuki Hashidoko - One of the best experts on this subject based on the ideXlab platform.
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Isolation and characterization of 1-palmitoyl-2-linoleoyl-sn-glycerol as a hormogonium-inducing factor (HIF) from the coralloid roots of Cycas revoluta (Cycadaceae)
Scientific reports, 2019Co-Authors: Yasuyuki Hashidoko, Hiroaki Nishizuka, Manato Tanaka, Kanako Murata, Yuta Murai, Makoto HashimotoAbstract:Coralloid roots are specialized tissues of cycads (Cycas revoluta) that are involved in symbioses with nitrogen-fixing Nostoc cyanobacteria. We found that a crude methanolic extract of coralloid roots induced differentiation of the filamentous cell aggregates of Nostoc species into motile hormogonia. Hence, the hormogonium-inducing factor (HIF) was chased using bioassay-based isolation, and the active principle was characterized as a mixture of diacylglycerols (DAGs), mainly composed of 1-palmitoyl-2-linoleoyl-sn-glycerol (1), 1-palmitoyl-2-oleoyl-sn-glycerol (2), 1-stearoyl-2-linolenoyl-sn-glycerol (3), and 1-stearoyl-2-linoleoyl-sn-glycerol (4). Enantioselectively synthesised compound 1 showed a clear HIF activity at 1 nmol (0.6 µg) disc−1 for the filamentous cells, whereas synthesised 2-linoleoyl-3-palmitoyl-sn-glycerol (1′) and 1-palmitoyl-2-linoleoyl-rac-glycerol (1/1′) were less active than 1. Conversely, synthesised 1-linoleoyl-2-palmitoyl-rac-glycerol (8/8′) which is an acyl positional isomer of compound 1 was inactive. In addition, neither 1-monoacylglycerols nor phospholipids structurally related to 1 showed HIF-like activities. As DAGs are protein kinase C (PKC) activators, 12-O-tetradecanoylphorbol-13-acetate (12), urushiol C15:3-Δ10,13,16 (13), and a Skin Irritant anacardic acid C15:1-Δ8 (14) were also examined for HIF-like activities toward the Nostoc cells. Neither 12 nor 13 showed HIF-like activities, whereas 14 showed an HIF-like activity at 1 nmol/disc. These findings appear to indicate that some DAGs act as hormogonium-inducing signal molecules for filamentous Nostoc cyanobacteria.
V. Bampidis - One of the best experts on this subject based on the ideXlab platform.
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Safety and efficacy of the feed additive consisting of l‐tryptophan produced by Escherichia coli KCCM 80210 for all animal species (Daesang Europe BV)
'Wiley', 2021Co-Authors: Efsa Panel on Additives And Products Or Substances Used In Animal Feed, Maria De Lourdes Bastos, G. Azimonti, V. Bampidis, H. Christensen, B. Dusemund, M. Kouba, Mojca Fašmon Durjava, Marta López‐alonso, Secundino López PuenteAbstract:Abstract Following a request from the European Commission, the Panel on Additives and Products or substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of the feed additive consisting of l‐tryptophan produced by fermentation with Escherichia coli KCCM 80210 when used as a nutritional additive in feed for all animal species and categories. The production strain E. coli KCCM 80210 is safe for the production of l‐tryptophan and it was not detected in the final product. The Panel notes that two out of five batches of the additive do not comply with the minimum specification of 98% l‐tryptophan on a dry matter basis proposed by the applicant. The use of l‐tryptophan (≥ 98%) produced by E. coli KCCM 80210 in supplementing feed to compensate for l‐tryptophan deficiency in feedingstuffs is safe for non‐ruminant target species. There may be a risk for an increased production of toxic metabolites when unprotected l‐tryptophan is used in ruminants. The use of l‐tryptophan produced by E. coli KCCM 80210 in animal nutrition raises no safety concerns to consumers of animal products and to the environment. The additive under assessment is considered a mild eye Irritant. The endotoxin activity of the additive and its dusting potential indicate a risk by inhalation for the users. The additive is not a Skin Irritant and is not a Skin sensitiser. The additive l‐tryptophan is regarded as an effective source of the amino acid l‐tryptophan for all non‐ruminant species. In order to be as efficacious in ruminants as in non‐ruminants, it should be protected from ruminal degradation
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Safety and efficacy of a feed additive consisting of serine protease produced by Bacillus licheniformis DSM 19670 (Ronozyme® ProAct) for chickens for fattening (DSM Nutritional Products Ltd.)
'Wiley', 2021Co-Authors: Efsa Panel on Additives And Products Or Substances Used In Animal Feed, Maria De Lourdes Bastos, G. Azimonti, V. Bampidis, H. Christensen, B. Dusemund, M. Kouba, Mojca Fašmon Durjava, Marta López‐alonso, Secundino López PuenteAbstract:Abstract Ronozyme® ProAct is the trade name of the feed additive under assessment and contains serine protease produced by a genetically modified strain of Bacillus licheniformis. Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of Ronozyme® ProAct when used as a zootechnical additive for chickens for fattening. The additive is available in coated thermotolerant granulated and liquid forms (Ronozyme® ProAct CT/L). The production strain and its recombinant DNA were not detected in an intermediate concentrated product used to produce the final formulations. The final products do not trigger a safety concern with regard to the genetic modification. Based on the results obtained in a tolerance study in chickens for fattening and the data from a subchronic oral toxicity study the FEEDAP Panel concluded that the additive is safe for chickens for fattening. The FEEDAP Panel concluded that the use of Ronozyme® ProAct CT/L as a feed additive gives rise to no concern for consumers and for the environment. The additive, in either form, is not an eye Irritant but should be considered a Skin Irritant. In the absence of data, no conclusions on the Skin sensitisation potential can be reached. Owing to the proteinaceous nature of the active substance it should be considered a respiratory sensitiser. The FEEDAP Panel also concluded that the additive has the potential to be efficacious at 15,000 PROT/kg compound feed for chickens for fattening
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Safety and efficacy of Actisaf ® Sc47 (Saccharomyces cerevisiae CNCM I-4407) as a feed additive for cattle for fattening, dairy cows, weaned piglets and sows
'Wiley', 2019Co-Authors: V. Bampidis, G. Azimonti, M.d.l. Bastos, H. Christensen, B. Dusemund, M. Kouba, Kos M. Durjava, M. Lopez-alonso, Lopez S. Puente, F. MarconAbstract:Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of Actisaf ® Sc47 for dairy cows, cattle for fattening, weaned piglets and sows when used as a zootechnical additive. Actisaf ® Sc47 consists of viable cells of a strain Saccharomyces cerevisiae and is marketed in three formulations. The FEEDAP Panel considers that the three available formulations are equivalent when used to deliver the same dose of the microorganism in feed. The active agent fulfils the requirements of the qualified presumption of safety approach to the assessment of safety. Since the additive is composed of the active agent only, Actisaf ® Sc47 is also presumed safe for the target animals, consumers of products derived from treated animals and the environment. Actisaf ® Sc47 is not a Skin Irritant. In the absence of data, no conclusions can be drawn on the eye irritancy and dermal sensitisation potential of the additive. Inhalation exposure is unlikely. The additive has the potential to be efficacious in weaned piglets and sows to have benefits in piglets at the recommended dose of 5 × 10 9 CFU/kg feed. Insufficient evidence was provided to conclude on the efficacy of the additive in dairy cows and cattle for fattening
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Safety and efficacy of Bacillus subtilis DSM 28343 for pigs for fattening
'Wiley', 2019Co-Authors: V. Bampidis, Maria De Lourdes Bastos, G. Azimonti, H. Christensen, B. Dusemund, M. Kouba, Kos M. Durjava, M. Lopez-alonso, Lopez S. Puente, F. MarconAbstract:Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of Bacillus subtilis DSM 28343 when used in feed for pigs for fattening. The additive is a preparation containing viable spores of a strain of Bacillus subtilis. This species is considered by EFSA to be suitable for the qualified presumption of safety (QPS) approach to safety assessment which requires the identity of the strain to be conclusively established, evidence that the strain is not toxigenic and that it does not show resistance to antibiotics of human and veterinary importance. The strain was found to meet the criteria for the QPS approach in the context of a previous opinion and since concerns are not expected from other components of the additive, the additive is presumed safe for all target species, consumers and the environment. In a previous opinion, the FEEDAP Panel concluded that Bacillus subtilis DSM 28343 is not an eye/Skin Irritant but should be considered as a potential respiratory sensitizer and that no conclusion could be drawn on its Skin sensitisation potential. These conclusions apply also to the current application. Bacillus subtilis DSM 28343 at 2 7 108 CFU/kg complete feed has the potential to be efficacious in pigs for fattening
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safety and efficacy of lactococcus lactis ncimb 30160 as a feed additive for all animal species
EFSA Journal, 2018Co-Authors: Guido Rychen, Maria De Lourdes Bastos, Pier Sandro Cocconcelli, Gerhard Flachowsky, Gabriele Aquilina, Georges Bories, Andrew Chesson, G. Azimonti, V. Bampidis, Jurgen GroppAbstract:Following a request from European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the proposed modification of the terms of the authorisation regarding the formulation of the product Lactococcus lactis NCIMB 30160. The applicant has proposed to modify the manufacturing process by replacing one ingredient in the freeze-drying step with polyethylene glycol (PEG 4000), a product authorised in the EU as a food additive. The use of PEG 4000 as an excipient in formulations with Lactococcus lactis NCIMB 30160 would not change the previous conclusions regarding the safety for the target animals, consumers and users. The FEEDAP Panel concludes that the additive is safe for target species and for consumers of products from animals fed the treated silage. The additive is not a Skin Irritant but is a potential Skin/respiratory sensitiser. In the absence of data, the Panel is unable to conclude on the safety for the environment of the proposed use of PEG 4000 as excipient in formulations of the additive. The FEEDAP Panel sees no reason to reconsider the conclusions on efficacy previously drawn that the additive containing L. lactis NCIMB 30160 has the potential to improve the production of silage from all forages by increasing lactic acid content and the preservation of dry matter, by reducing the pH and moderately the loss of protein, as determined by ammonia-N.
