The Experts below are selected from a list of 222 Experts worldwide ranked by ideXlab platform
Miguel A. Miranda - One of the best experts on this subject based on the ideXlab platform.
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mechanistic studies on the Photoallergy mediated by fenofibric acid photoreactivity with serum albumins
Chemical Research in Toxicology, 2016Co-Authors: Ignacio Vaya, Consuelo M Jimenez, Inmaculada Andreu, Vicente T Monje, Miguel A. MirandaAbstract:The photoreactivity of fenofibric acid (FA) in the presence of human and bovine serum albumins (HSA and BSA, respectively) has been investigated by steady-state irradiation, fluorescence, and laser flash photolysis (LFP). Spectroscopic measurements allowed for the determination of a 1:1 stoichiometry for the FA/SA complexes and pointed to a moderate binding of FA to the proteins; by contrast, the FA photoproducts were complexed more efficiently with SAs. Covalent photobinding to the protein, which is directly related to the photoallergic properties of the drug, was detected after long irradiation times and was found to be significantly higher in the case of BSA. Intermolecular FA-amino acid and FA-albumin irradiations resulted in the formation of photoproducts arising from coupling between both moieties, as indicated by mass spectrometric analysis. Mechanistic studies using model drug–amino acid linked systems indicated that the key photochemical step involved in Photoallergy is formal hydrogen atom trans...
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photonucleophilic addition of the e amino group of lysine to a triflusal metabolite as a mechanistic key to Photoallergy mediated by the parent drug
ChemMedChem, 2009Co-Authors: Sara Montanaro, Virginie Lhiaubetvallet, Consuelo M Jimenez, Miguel Blanca, Miguel A. MirandaAbstract:: A mechanism for triflusal-induced Photoallergy involving complexation of 2-hydroxy-4-trifluoromethylbenzoic acid with site I of human serum albumin and subsequent formation of a covalent adduct by photoreaction between a metabolite and a neighboring lysine residue is proposed. This is supported by the observed photobinding to poly-L-lysine. Thereby, a photoantigen is generated, which is a likely trigger of the immune response.The goal of the work presented herein is to gain deeper insight into the molecular basis of Photoallergy mediated by triflusal through its active metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). For this purpose, the interaction between HTB and human serum albumin (HSA) was investigated by fluorescence and laser flash photolysis to monitor inclusion into the protein binding sites through variation in the excited-state properties. A remarkable lengthening of HTB triplet lifetime in the presence of HSA was observed. The use of oleic acid as a displacement probe clearly suggests the preference for dark binding in site I. The mechanism of photobinding was studied by irradiation of HTB in the presence of amino acids, and, in the case of lysine, a photoadduct was detected that arises from nucleophilic attack by the epsilon-amino group to the trifluoromethyl substituent of HTB. Accordingly, photobinding of the metabolite to poly-L-lysine was also observed. Overall, these results are consistent with a mechanism for triflusal Photoallergy involving complexation of HTB to site I of HSA and subsequent formation of a covalent photoadduct with one neighboring lysine residue.
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Photonucleophilic Addition of the ε-Amino Group of Lysine to a Triflusal Metabolite as a Mechanistic Key to Photoallergy Mediated by the Parent Drug
ChemMedChem, 2009Co-Authors: Sara Montanaro, Miguel Blanca, Virginie Lhiaubet-vallet, M. Consuelo Jiménez, Miguel A. MirandaAbstract:A mechanism for triflusal-induced Photoallergy involving complexation of 2-hydroxy-4-trifluoromethylbenzoic acid with site I of human serum albumin and subsequent formation of a covalent adduct by photoreaction between a metabolite and a neighboring lysine residue is proposed. This is supported by the observed photobinding to poly-L-lysine. Thereby, a photoantigen is generated, which is a likely trigger of the immune response. The goal of the work presented herein is to gain deeper insight into the molecular basis of Photoallergy mediated by triflusal through its active metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). For this purpose, the interaction between HTB and human serum albumin (HSA) was investigated by fluorescence and laser flash photolysis to monitor inclusion into the protein binding sites through variation in the excited-state properties. A remarkable lengthening of HTB triplet lifetime in the presence of HSA was observed. The use of oleic acid as a displacement probe clearly suggests the preference for dark binding in site I. The mechanism of photobinding was studied by irradiation of HTB in the presence of amino acids, and, in the case of lysine, a photoadduct was detected that arises from nucleophilic attack by the e-amino group to the trifluoromethyl substituent of HTB. Accordingly, photobinding of the metabolite to poly-L-lysine was also observed. Overall, these results are consistent with a mechanism for triflusal Photoallergy involving complexation of HTB to site I of HSA and subsequent formation of a covalent photoadduct with one neighboring lysine residue.
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an in vitro approach to drug Photoallergy use of drug directed antibodies to assess photobinding of non steroidal anti inflammatories to skin cells
Toxicology in Vitro, 1999Co-Authors: Miguel A. Miranda, Daniel Hernández, Isabel M. Morera, Zaideth Sarabia, M J Gomezlechon, J V CastellAbstract:Photobinding of drugs to biomolecules constitutes the early key event in the onset of Photoallergy. This process generally involves excitation of the drug to an excited triplet state, which in turn can interact with cell constituents leading, in the case of proteins, to the formation of covalent photoadducts. The resulting photoantigens may trigger an immune response. In the present communication, we report the use of drug-directed antibodies to detect photoadduct formation in skin cells. This has been exemplified with tiaprofenic acid and suprofen as model compounds (two well known photoallergens) and human fibroblasts as representative skin cells. Upon irradiation of cells in the presence of these non-steroidal anti-inflammatories, time-dependent photoadduct formation was observed. This occurred predominantly at the cell membrane level. Most interestingly, the immunogenicity of cell photoadducts could be demonstrated by injection of Balb/c mouse fibroblasts into immunologically identical syngenic animals, where they triggered an immune response, as evidenced by the formation of specific antibodies and sensitized T-cells.
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Drug-Photosensitized Protein Modification: Identification of the Reactive Sites and Elucidation of the Reaction Mechanisms with Tiaprofenic Acid/Albumin as Model System†
Chemical Research in Toxicology, 1998Co-Authors: Miguel A. Miranda, José V. Castell, Daniel Hernández, María José Gómez-lechón, Francisco Bosca, Isabel M. Morera, Zaideth SarabiaAbstract:Certain drugs can photosensitive the formation of protein modifications, which are thought to be responsible for the occurrence of Photoallergy. In the present work, the UV irradiation of serum albumin in the presence of tiaprofenic acid has been studied as a model system for drug-photosensitized protein modifications. The photolysates evidenced that His, Tyr, and Trp are the reactive sites of the protein. The experimental results strongly suggest that formal hydrogen abstraction from the OH or NH groups of Tyr or Trp by the excited drug is the key photochemical process. Competition between cage escape and in cage recombination of the resulting radical pairs governs the final outcome: protein photo-cross-linking versus drug−protein adduct formation. These findings are highly relevant to understand the process of photohapten formation, the first event in the onset of Photoallergy.
Yoshiki Tokura - One of the best experts on this subject based on the ideXlab platform.
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chemical Photoallergy photobiochemical mechanisms classification and risk assessments
Journal of Dermatological Science, 2017Co-Authors: Satomi Onoue, Yoshiki Seto, Hideyuki Sato, Hayato Nishida, Morihiko Hirota, Takao Ashikaga, David A Basketter, Yoshiki TokuraAbstract:Abstract Chemical photosensitivity can be elicited by exposure of the skin to various pharmaceutical substances, foods, cosmetics and other environmental chemicals, followed by exposure to sunlight. There are at least three types of chemical photosensitivity, i.e. , photoirritancy (narrowly defined as phototoxicity), photogenotoxicity and photoallergenicity, and their clinical characteristics and mechanisms are quite different. Concerns about chemical Photoallergy is increasing, and various studies have been made to clarify the photobiochemical characteristics of photoallergens and the mechanisms involved. Various methodologies, including in silico prediction models, photochemical assay systems, and in vitro phototoxicity prediction tools, have been developed to predict the photoallergenic potential of chemicals over the past few years. The aim of this manuscript is to review the clinical characteristics, pathogenetic mechanisms and photobiochemical features of photoallergens, with special emphasis on the current status about development of screening systems for predicting photoallergenic potential of chemicals.
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induction of eosinophil infiltrating drug Photoallergy in mice
Journal of Dermatological Science, 2009Co-Authors: Daisuke Nishio, Daiki Nakashima, Tomoko Mori, Kenji Kabashima, Yoshiki TokuraAbstract:Abstract Background Drug Photoallergy is one of the highly incident adverse effects. Several different histological patterns have been recognized. Objective To establish a murine model of the eosinophil-infiltrating type of drug Photoallergy by using afloqualone (AQ), a representative photosensitive drug. Methods AKR/J mice were sensitized by intraperitoneal injection of afloqualone solution (2mg/kg/mouse) and irradiation of shaved abdomen with ultraviolet A light (UVA) (12J/cm 2 ). This sensitization procedure was repeated 2–12 times, and 3 days after the last immunization, mice were challenged by a subcutaneous injection of AQ solution and irradiation of the same site with UVA. The draining lymph node cells (LNCs) were used for transfer and cytokine production studies, and the challenged skin was analyzed for chemokine expression. Results More than 10 times of sensitization induced a massive infiltrate of eosinophils and lymphocytes at the challenged site. AKR/J mice were a high responder strain. The sensitivity was transferred with 5–8×10 7 immune lymph node and spleen cells into naive mice. CD4 + T cells were mainly responsible for this sensitivity, since 1×10 7 CD4 + cells alone induced a high level of sensitivity, but CD8 + T cells evoked the sensitivity to a lesser degree. Culture supernatants from AQ-photoimmuned lymph node cells contained a higher level of IL-4 and lower interferon-γ than those from mice immunized with dinitrofluorobenzene. Finally, the skin of AQ-photochallenged site exhibited high expression of CCL24/eotaxin-2, a chemokine for eosinophils. Conclusion It is suggested that eosinophilic drug Photoallergy is mediated by sensitized Th2 cells and locally produced eosinophil-attracting chemokines.
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quinolone Photoallergy photosensitivity dermatitis induced by systemic administration of photohaptenic drugs
Journal of Dermatological Science, 1998Co-Authors: Yoshiki TokuraAbstract:Abstract Quinolone antibacterial agents are well known to elicit photosensitivity as a side effect. The photoallergenicity of fluoroquinolones, the representative quinolone derivatives, is mainly derived from their photohaptenic moiety. When epidermal cells are irradiated with ultraviolet A light in the presence of fluoroquinolones, quinolone photoadducts are formed in the treated cells. This photomodification is thought to be an initial step for sensitization and elicitation of this Photoallergy, and quinolone-photoderivatized Langerhans cells are capable of stimulating immune T cells in mice. In the murine model, fluoroquinolone Photoallergy is mediated by Th1 cells bearing T cell receptor Vβ13. There is a broad photoantigenic cross-reactivity among fluoroquinolones in recognition by T cells and immunoglobulins. Therefore, it is most likely that fluoroquinolones carry the same photoantigenic epitope, which is recognized by Vβ13+ T cells, leading to fluoroquinolone photosensitivity and cross-reactivity.
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review article quinolone Photoallergy photosensitivity dermatitis induced by systemic administration of photohaptenic drugs
1998Co-Authors: Yoshiki TokuraAbstract:Quinolone antibacterial agents are well known to elicit photosensitivity as a side effect. The photoallergenicity of fluoroquinolones, the representative quinolone derivatives, is mainly derived from their photohaptenic moiety. When epidermal cells are irradiated with ultraviolet A light in the presence of fluoroquinolones, quinolone photoadducts are formed in the treated cells. This photomodification is thought to be an initial step for sensitization and elicitation of this Photoallergy, and quinolone-photoderivatized Langerhans cells are capable of stimulating immune T cells in mice. In the murine model, fluoroquinolone Photoallergy is mediated by Th1 cells bearing T cell receptor Vb13. There is a broad photoantigenic cross-reactivity among fluoroquinolones in recognition by T cells and immunoglobulins. Therefore, it is most likely that fluoroquinolones carry the same photoantigenic epitope, which is recognized by Vb13 T cells, leading to fluoroquinolone photosensitivity and cross-reactivity. © 1998 Elsevier Science Ireland Ltd. All rights reserved.
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evaluation of ultraviolet a protection by sunscreen agents using a mouse model of contact Photoallergy
Journal of Dermatological Science, 1994Co-Authors: Yoshiki Tokura, Hiroaki Yagi, Hazuki Ihda, Masahiro TakigawaAbstract:Abstract This study was conducted to investigate in vivo evaluation of protectiveness by sunscreens in the UVA range using a mouse model of contact Photoallergy (CPS) to 3,3′,4′,5-tetrachlorosalicylanilide (TCSA). Mice were sensitized with TCSA painting plus UVA irradiation (TCSA/UVA) on the abdomen and, 5 days later, challenged with TCSA/UVA on the earlobe. Each of four sunscreen agents, benzophenone-3, Parsol 1789, p -aminobenzoic acid, and 2-ethyl-hexyl- p -methoxycinnamate, was applied to the earlobes before irradiation. Their protective efficacy was evaluated in the degree of inhibition of both ear swelling responses and TCSA-epidermal cell photoadduct formation. Two UVA-absorbing sunscreens, benzophenone-3 and Parsol 1789, dramatically inhibited the ear swelling response, while the two UVB-absorbers exhibited a much less suppressive effect. The UVA-absorbing agents functioned via inhibiting the formation of TCSA-epidermal cell photoadducts. This method is thought to be useful for in vivo estimation of UVA protection provided by sunscreens against the exquisite sensitivity involved in Photoallergy.
Yasuhiro Tokura - One of the best experts on this subject based on the ideXlab platform.
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Induction of eosinophil-infiltrating drug Photoallergy in mice
Journal of Dermatological Science, 2009Co-Authors: Daisuke Nishio, Daiki Nakashima, Tomoko Mori, Kenji Kabashima, Yasuhiro TokuraAbstract:Background: Drug Photoallergy is one of the highly incident adverse effects. Several different histological patterns have been recognized. Objective: To establish a murine model of the eosinophil-infiltrating type of drug Photoallergy by using afloqualone (AQ), a representative photosensitive drug. Methods: AKR/J mice were sensitized by intraperitoneal injection of afloqualone solution (2 mg/kg/mouse) and irradiation of shaved abdomen with ultraviolet A light (UVA) (12 J/cm2). This sensitization procedure was repeated 2-12 times, and 3 days after the last immunization, mice were challenged by a subcutaneous injection of AQ solution and irradiation of the same site with UVA. The draining lymph node cells (LNCs) were used for transfer and cytokine production studies, and the challenged skin was analyzed for chemokine expression. Results: More than 10 times of sensitization induced a massive infiltrate of eosinophils and lymphocytes at the challenged site. AKR/J mice were a high responder strain. The sensitivity was transferred with 5-8 ?? 107 immune lymph node and spleen cells into na??ve mice. CD4+ T cells were mainly responsible for this sensitivity, since 1 ?? 107 CD4+ cells alone induced a high level of sensitivity, but CD8+ T cells evoked the sensitivity to a lesser degree. Culture supernatants from AQ-photoimmuned lymph node cells contained a higher level of IL-4 and lower interferon-?? than those from mice immunized with dinitrofluorobenzene. Finally, the skin of AQ-photochallenged site exhibited high expression of CCL24/eotaxin-2, a chemokine for eosinophils. Conclusion: It is suggested that eosinophilic drug Photoallergy is mediated by sensitized Th2 cells and locally produced eosinophil-attracting chemokines. ?? 2009 Japanese Society for Investigative Dermatology.
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Photoallergy
Expert Review of Dermatology, 2009Co-Authors: Yasuhiro TokuraAbstract:There are two mechanisms underlying photosensitivity to exogenous agents: phototoxicity and Photoallergy. While the phototoxic reaction is mediated mainly by free radicals, the photoallergic reaction is induced and elicited by immunological consequences. Photosensitive chemicals have a haptenic moiety, and two hypotheses have been put forward to explain the formation of photoallergens: prohaptens and photohaptens. Photohaptens need to coexist with a protein and, upon UV irradiation, a covalent bond is formed. The vast majority of clinically photoallergic chemicals are photohaptens rather than prohaptens. In a clinical photopatch test, a causative chemical is applied to the skin and UVA is irradiated to the site. This method tests the photohaptenic property. Clinically, photocontact dermatitis and drug photosensitivity are the two major disorders caused by topical and systemic exogenous photosensitizers, respectively. In photocontact dermatitis, halogenated salicylanilide and the related compounds musk ambrette, 6-methylcoumarin and benzophenone-3 (oxybenzone), were causative and, recently, topical NSAIDs have been another leading cause. In drug photosensitivity there have been many photosensitive drugs, including quinolones, piroxicam, afloqualone, griseofluvin, tegafur and tilisolol. The underlying mechanisms involve topically applied or orally administered chemicals diffusing from the skin surface or blood to the epidermis, and epidermal cells are photoderivatized with a given chemical upon UVA irradiation. Antigen-presenting dendritic cells are photomodified with the chemical upon exposure of the skin to UVA and become photohapten-bearing, T-cell stimulatory cells. © 2009 Expert Reviews Ltd.
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quinolone photoconjugated major histocompatibility complex class ii binding peptides with lysine are antigenic for t cells mediating murine quinolone Photoallergy
Journal of Investigative Dermatology, 2001Co-Authors: Yasuhiro Tokura, Masahiro Takigawa, Michio FujieAbstract:Fluoroquinolone antibacterial agents cause photosensitivity dermatitis as an adverse effect and can function immunologically as photohapten. In a murine model of quinolone Photoallergy, Langerhans cells are photomodified with a systemically given quinolone upon ultraviolet A irradiation of skin and thus present photohaptenic moieties to sensitize and restimulate T cells. The aim of this study is to determine the site of peptides/proteins photobound to quinolones and to assess the T cell antigenicity of quinolone-photocoupled peptides using Langerhans cells as photoadduct-presenting cells. On an amino acid composition analysis, lysine was preferentially degraded in bovine serum albumin that was ultraviolet A-conjugated with a representative quinolone ofloxacin. An affinity chromatographic study using a quinolone photoadduct-specific monoclonal antibody as ligand demonstrated preferential photocoupling of ofloxacin with a lysine-containing peptide. CD4+ T cells were purified from lymph nodes of BALB/c mice sensitized subcutaneously with ofloxacin-photomodified epidermal cells and from those sensitized epicutaneously via barrier-disrupted skin with a major histocompatibility complex class II (I-Ad)-binding, ofloxacin-photoconjugated peptide. These immune T cells proliferated in vitro in response to Langerhans cells loaded with class II-binding, lysine-containing peptides when photomodified with ofloxacin. Furthermore, epicutaneous application of the ofloxacin-photoconjugated peptide was able to prime mice for subsequent elicitation of Photoallergy evoked with systemic ofloxacin and ultraviolet A light. This study suggests that lysine affords quinolone photocoupling of peptides and quinolone-photomodified peptides on class II molecules stimulate pathogenetic T cells in quinolone Photoallergy.
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formation of antigenic quinolone photoadducts on langerhans cells initiates Photoallergy to systemically administered quinolone in mice
Journal of Investigative Dermatology, 2000Co-Authors: Akihiro Ohshima, Masahiro Takigawa, Yasuhiro TokuraAbstract:Quinolone antibacterial agents are well known to cause Photoallergy as a side-effect. Murine Photoallergy to fluoroquinolones is a T cell-mediated immune response, evoked either by systemic fluoroquinolone and subsequent exposure of skin to ultraviolet A light or by subcutaneous injection of fluoroquinolone-photomodified epidermal cells. In this photosensitivity, epidermal Langerhans cells may be photomodified initially with the drug and thus present photohaptenic moieties to sensitize and restimulate T cells. Although we have shown that Langerhans cells photocoupled in vitro with fluoroquinolones are capable of stimulating sensitized T cells, it remains unclear whether systemically given fluoroquinolone photomodifies Langerhans cells upon ultraviolet A irradiation of the skin and the Langerhans cells become photohapten-bearing, T cell-stimulatory cells. In a murine model of fleroxacin Photoallergy induced by intraperitoneal injection of the drugs plus ultraviolet A irradiation of skin, we found that Langerhans cells as well as keratinocytes are photoderivatized with fleroxacin as demonstrated with a fluoroquinolone-specific monoclonal antibody. Langerhans-cell-enriched epidermal cells prepared from mice treated with fleroxacin and ultraviolet A induced proliferation of sensitized T cells, indicating that photomodified Langerhans cells are functional. There was an optimal range of ultraviolet A dose to quantitatively and qualitatively form fleroxacin-photomodified Langerhans cells, as excess ultraviolet A rather reduced the photoantigen-presenting capacity of Langerhans cells presumably because of drug phototoxicity. Our study suggests that Langerhans cells serve as photoantigen-presenting cells in drug Photoallergy.
B Ljunggren - One of the best experts on this subject based on the ideXlab platform.
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systemically induced Photoallergy to quinine in the mouse can be elicited topically and vice versa
Acta Dermato-venereologica, 1990Co-Authors: L E Wirestrand, B LjunggrenAbstract:: Groups of female albino mice were photosensitized and photochallenged to quinine using protocols for either systemic or epicutaneous administration. Compared with control groups, statistically significant inflammatory reactions, measured as wet weight increase in ear tissue, could be obtained both with systemic and epicutaneous administration. Topically induced Photoallergy to quinine could be elicited not only by topical, but also by intraperitoneal administration of the drug, and vice versa. The strongest response at challenge was obtained when the induction was performed topically and the challenge by the systemic route. These data suggest that epicutaneous and systemic Photoallergy to quinine have mechanisms in common, and that the route of introduction of the sensitizer into the skin is not the crucial factor. This experimental model may be useful in the elucidation of the mechanisms of systemic Photoallergy.
Masahiro Takigawa - One of the best experts on this subject based on the ideXlab platform.
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quinolone photoconjugated major histocompatibility complex class ii binding peptides with lysine are antigenic for t cells mediating murine quinolone Photoallergy
Journal of Investigative Dermatology, 2001Co-Authors: Yasuhiro Tokura, Masahiro Takigawa, Michio FujieAbstract:Fluoroquinolone antibacterial agents cause photosensitivity dermatitis as an adverse effect and can function immunologically as photohapten. In a murine model of quinolone Photoallergy, Langerhans cells are photomodified with a systemically given quinolone upon ultraviolet A irradiation of skin and thus present photohaptenic moieties to sensitize and restimulate T cells. The aim of this study is to determine the site of peptides/proteins photobound to quinolones and to assess the T cell antigenicity of quinolone-photocoupled peptides using Langerhans cells as photoadduct-presenting cells. On an amino acid composition analysis, lysine was preferentially degraded in bovine serum albumin that was ultraviolet A-conjugated with a representative quinolone ofloxacin. An affinity chromatographic study using a quinolone photoadduct-specific monoclonal antibody as ligand demonstrated preferential photocoupling of ofloxacin with a lysine-containing peptide. CD4+ T cells were purified from lymph nodes of BALB/c mice sensitized subcutaneously with ofloxacin-photomodified epidermal cells and from those sensitized epicutaneously via barrier-disrupted skin with a major histocompatibility complex class II (I-Ad)-binding, ofloxacin-photoconjugated peptide. These immune T cells proliferated in vitro in response to Langerhans cells loaded with class II-binding, lysine-containing peptides when photomodified with ofloxacin. Furthermore, epicutaneous application of the ofloxacin-photoconjugated peptide was able to prime mice for subsequent elicitation of Photoallergy evoked with systemic ofloxacin and ultraviolet A light. This study suggests that lysine affords quinolone photocoupling of peptides and quinolone-photomodified peptides on class II molecules stimulate pathogenetic T cells in quinolone Photoallergy.
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formation of antigenic quinolone photoadducts on langerhans cells initiates Photoallergy to systemically administered quinolone in mice
Journal of Investigative Dermatology, 2000Co-Authors: Akihiro Ohshima, Masahiro Takigawa, Yasuhiro TokuraAbstract:Quinolone antibacterial agents are well known to cause Photoallergy as a side-effect. Murine Photoallergy to fluoroquinolones is a T cell-mediated immune response, evoked either by systemic fluoroquinolone and subsequent exposure of skin to ultraviolet A light or by subcutaneous injection of fluoroquinolone-photomodified epidermal cells. In this photosensitivity, epidermal Langerhans cells may be photomodified initially with the drug and thus present photohaptenic moieties to sensitize and restimulate T cells. Although we have shown that Langerhans cells photocoupled in vitro with fluoroquinolones are capable of stimulating sensitized T cells, it remains unclear whether systemically given fluoroquinolone photomodifies Langerhans cells upon ultraviolet A irradiation of the skin and the Langerhans cells become photohapten-bearing, T cell-stimulatory cells. In a murine model of fleroxacin Photoallergy induced by intraperitoneal injection of the drugs plus ultraviolet A irradiation of skin, we found that Langerhans cells as well as keratinocytes are photoderivatized with fleroxacin as demonstrated with a fluoroquinolone-specific monoclonal antibody. Langerhans-cell-enriched epidermal cells prepared from mice treated with fleroxacin and ultraviolet A induced proliferation of sensitized T cells, indicating that photomodified Langerhans cells are functional. There was an optimal range of ultraviolet A dose to quantitatively and qualitatively form fleroxacin-photomodified Langerhans cells, as excess ultraviolet A rather reduced the photoantigen-presenting capacity of Langerhans cells presumably because of drug phototoxicity. Our study suggests that Langerhans cells serve as photoantigen-presenting cells in drug Photoallergy.
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evaluation of ultraviolet a protection by sunscreen agents using a mouse model of contact Photoallergy
Journal of Dermatological Science, 1994Co-Authors: Yoshiki Tokura, Hiroaki Yagi, Hazuki Ihda, Masahiro TakigawaAbstract:Abstract This study was conducted to investigate in vivo evaluation of protectiveness by sunscreens in the UVA range using a mouse model of contact Photoallergy (CPS) to 3,3′,4′,5-tetrachlorosalicylanilide (TCSA). Mice were sensitized with TCSA painting plus UVA irradiation (TCSA/UVA) on the abdomen and, 5 days later, challenged with TCSA/UVA on the earlobe. Each of four sunscreen agents, benzophenone-3, Parsol 1789, p -aminobenzoic acid, and 2-ethyl-hexyl- p -methoxycinnamate, was applied to the earlobes before irradiation. Their protective efficacy was evaluated in the degree of inhibition of both ear swelling responses and TCSA-epidermal cell photoadduct formation. Two UVA-absorbing sunscreens, benzophenone-3 and Parsol 1789, dramatically inhibited the ear swelling response, while the two UVB-absorbers exhibited a much less suppressive effect. The UVA-absorbing agents functioned via inhibiting the formation of TCSA-epidermal cell photoadducts. This method is thought to be useful for in vivo estimation of UVA protection provided by sunscreens against the exquisite sensitivity involved in Photoallergy.