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BMB Reports Sep 2012We evaluated the expression of the costimulatory molecules CD80 and CD83 and major histocompatibility (MHC) class II induced by 2,4-dinitrofluorobenzene (DNFB) in the...
We evaluated the expression of the costimulatory molecules CD80 and CD83 and major histocompatibility (MHC) class II induced by 2,4-dinitrofluorobenzene (DNFB) in the RAW 264.7 macrophage cell line. In contrast to the previously reported effect of DNFB on dendritic cells, CD86 expression did not change. Furthermore, we observed that the CD83 expression level transiently increased and then decreased. Induction of CD80 and MHC class II molecule expression and a decrease in CD83 expression by DNFB in vitro were also confirmed in splenocytes of BALB/c and NC/Nga mice. However, DNFB did not influence CD83 expression in peritoneal CD11b(+) cells from BALB/c or NC/Nga mice. Detailed in vivo experiments and further studies on the possible contribution of CD11b(+) cells to induce atopic dermatitis (AD) would be helpful to attain a better understanding of AD pathogenesis.
Topics: Animals; Antigens, CD; Antigens, Surface; B7-1 Antigen; Biomarkers; CD11b Antigen; Cells, Cultured; Dendritic Cells; Dermatitis, Atopic; Dinitrofluorobenzene; Gene Expression Profiling; Histocompatibility Antigens Class II; Immunoglobulins; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Spleen; CD83 Antigen
PubMed: 23010176
DOI: 10.5483/bmbrep.2012.45.9.048 -
Cell Death and Differentiation Jan 2011FAS/CD95/Apo-1 is a ubiquitously expressed cell-surface receptor involved in the initiation of programmed cell death. Its function in epidermal keratinocytes has been...
FAS/CD95/Apo-1 is a ubiquitously expressed cell-surface receptor involved in the initiation of programmed cell death. Its function in epidermal keratinocytes has been incompletely defined. Available evidence from in vitro studies points to important roles of Fas in the pathogenesis of contact dermatitis and in keratinocyte apoptosis induced by ultraviolet light. To define functions of Fas in the epidermis in vivo, we have generated mice with epidermis-specific deletion of the fas gene and tested its requirement for 2,4-dinitrofluorobenzene-induced contact dermatitis and for ultraviolet light B (UVB)-induced keratinocyte apoptosis. We report here our unexpected finding that keratinocyte apoptosis induced by both a contact allergen and UVB irradiation was significantly enhanced in Fas-negative epidermis. Expression of Fas by epidermal keratinocytes was neither necessary for the normal development of contact hypersensitivity of the skin, nor required for keratinocyte apoptosis following UVB irradiation. Our study results thus show that in the epidermis in vivo Fas exerts antiapoptotic effects that outweigh its proapoptotic role in contact hypersensitivity responses of the skin and in the tissue response of the epidermis to UVB irradiation.
Topics: Allergens; Animals; Apoptosis; Dermatitis, Contact; Dinitrofluorobenzene; Keratinocytes; Mice; Mice, Knockout; Ultraviolet Rays; fas Receptor
PubMed: 20689557
DOI: 10.1038/cdd.2010.83 -
The Biochemical Journal Dec 1978The well-known immologically active component of pneumococci, C-polysaccharide, is a teichoic acid that can be isolated from the cell walls and purified by Sephadex and...
The well-known immologically active component of pneumococci, C-polysaccharide, is a teichoic acid that can be isolated from the cell walls and purified by Sephadex and ion-exchange chromatography. Further details of the structure of C-teichoic acid were established by chemical degradation, including hydrolysis in acid and alkali, treatment with HF, periodate oxidation and methylation. In addition, the use of 13C n.m.r. has confirmed some of these structural features and resulted in a proposal for the order of substituents, the location of positions of substitution and the configuration of anomeric centres in the repeating unit of the polymer.
Topics: Borohydrides; Cell Wall; Chemical Phenomena; Chemistry; Dinitrofluorobenzene; Hydrofluoric Acid; Hydrolysis; Magnetic Resonance Spectroscopy; Methylation; Periodic Acid; Polysaccharides, Bacterial; Streptococcus pneumoniae; Teichoic Acids
PubMed: 33662
DOI: 10.1042/bj1751033 -
Photochemistry and Photobiology 2012The lipid mediator Platelet-activating factor (PAF) and oxidized glycerophosphocholine PAF agonists produced by UVB have been demonstrated to play a pivotal role in...
The lipid mediator Platelet-activating factor (PAF) and oxidized glycerophosphocholine PAF agonists produced by UVB have been demonstrated to play a pivotal role in UVB-mediated systemic immunosuppression. Importantly, employing the ability of distant UVB irradiation to inhibit contact hypersensitivity (CHS) responses to the chemical antigen dinitrofluorobenzene (DNFB) to an area of unirradiated murine skin, we and others have demonstrated that UVB-mediated systemic immunosuppression was only observed in PAF-R expressing wild type (WT) mice and not in PAF-R-knockout (Pafr-/-) mice. As it is not known if PAF is involved in UVB-mediated local immunosuppression, these studies compared local UVB on CHS responses in WT versus Pafr-/- mice. We demonstrate that the application of DNFB onto UVB-exposed (locally) area of mouse skin resulted in a similar significant inhibition of subsequent CHS responses in both WT and Pafr-/- mice compared to sham-irradiated control mice. Furthermore, the expression of langerin, a marker for the presence of Langerhans cells was substantially reduced equally in the epidermal ears of UVB-irradiated WT and Pafr-/- mice compared to their respective sham control groups. These findings indicate that the PAF-R is not involved UVB-induced local immunosuppression.
Topics: Administration, Topical; Animals; Antigens, Surface; Dermatitis, Contact; Dinitrofluorobenzene; Female; Gene Expression; Immune Tolerance; Langerhans Cells; Lectins, C-Type; Mannose-Binding Lectins; Mice; Mice, Inbred C57BL; Mice, Knockout; Platelet Activating Factor; Platelet Membrane Glycoproteins; Receptors, G-Protein-Coupled; Skin; Ultraviolet Rays
PubMed: 22211638
DOI: 10.1111/j.1751-1097.2011.01071.x -
The Journal of Allergy and Clinical... Feb 2015Contact toxicant reactions are accompanied by localized skin inflammation and concomitant increases in site-specific itch responses. The role(s) of eosinophils in these...
BACKGROUND
Contact toxicant reactions are accompanied by localized skin inflammation and concomitant increases in site-specific itch responses. The role(s) of eosinophils in these reactions is poorly understood. However, previous studies have suggested that localized eosinophil-nerve interactions at sites of inflammation significantly alter tissue innervation.
OBJECTIVE
To define a potential mechanistic link between eosinophils and neurosensory responses in the skin leading to itching.
METHODS
BALB/cJ mice were exposed to different contact toxicants, identifying trimellitic anhydride (TMA) for further study on the basis of inducing a robust eosinophilia accompanied by degranulation. Subsequent studies using TMA were performed with wild type versus eosinophil-deficient PHIL mice, assessing edematous responses and remodeling events such as sensory nerve innervation of the skin and induced pathophysiological responses (ie, itching).
RESULTS
Exposure to TMA, but not dinitrofluorobenzene, resulted in a robust eosinophil skin infiltrate accompanied by significant levels of degranulation. Follow-up studies using TMA with wild type versus eosinophil-deficient PHIL mice showed that the induced edematous responses and histopathology were, in part, causatively linked with the presence of eosinophils. Significantly, these data also demonstrated that eosinophil-mediated events correlated with a significant increase in substance P content of the cutaneous nerves and an accompanying increase in itching, both of which were abolished in the absence of eosinophils.
CONCLUSIONS
Eosinophil-mediated events following TMA contact toxicant reactions increase skin sensory nerve substance P and, in turn, increase itching responses. Thus, eosinophil-nerve interactions provide a potential mechanistic link between eosinophil-mediated events and neurosensory responses following exposure to some contact toxicants.
Topics: Allergens; Animals; Cell Degranulation; Collagen; Dinitrofluorobenzene; Disease Models, Animal; Eosinophilia; Eosinophils; Fibrosis; Inflammation; Mice; Phthalic Anhydrides; Pruritus; Skin; Substance P
PubMed: 25129680
DOI: 10.1016/j.jaci.2014.07.003 -
Infection and Immunity Mar 1978Upon ingestion of particulate matter, polymorphonuclear leukocytes produce a chemiluminescence that can be measured in a liquid scintillation counter. In the experiments...
Upon ingestion of particulate matter, polymorphonuclear leukocytes produce a chemiluminescence that can be measured in a liquid scintillation counter. In the experiments reported here, the influence of three chemoattractants and three chemotactic modulators upon the chemiluminescence induced by opsonized zymosan was studied. The chemoattractants investigated (including bacterial factor derived from Escherichia coli, the simple peptide formylmethionylalanine, and activated human complement), which initiate directed movement when presented to cells in a concentration gradient, significantly enhanced zymosan-induced chemiluminescence. In the absence of opsonized zymosan, however, they had no effect on the chemiluminescence response. In contrast, the chemotactic modulators studied (including carbamylcholine, phenylephrine, and cyclic guanosine 5'-monophosphate, which are not chemotactic by themselves but can enhance or depress the movement of polymorphonuclear leukocytes initiated by chemoattractants) produced no enhancement of chemiluminescence. Other experiments were carried out in which neutrophils were pretreated with cytochalasin D, a compound that inhibits phagocytosis by interacting with microfilaments. Under these conditions, the chemiluminescence induced by opsonized zymosan was markedly reduced, but the response resulting from the addition of a chemoattractant to the leukocyte/zymosan mixture was not. This indicates that the chemiluminescence in response to chemoattractants is not dependent on phagocytosis per se. Neutrophils were also pretreated with dinitrofluorobenzene, a compound that binds amino groups and can be expected to react with proteins on the cell membrane. In these experiments, the chemiluminescence induced by opsonized zymosan and the pronounced spike of activity produced by the addition of a chemoattractant were completely abolished. These results suggest that the polymorphonuclear leukocyte chemiluminescence response to chemoattractants is mediated by cell surface proteins. Thus, chemoattractants may have a dual role in the acute inflammatory response: (i) the initiation and maintenance of directed cell movement, and (ii) enhancement of metabolic steps mediated at the cell membrane, resulting in microbicidal activity.
Topics: Bacterial Physiological Phenomena; Chemotaxis, Leukocyte; Complement System Proteins; Cytochalasin B; Dinitrofluorobenzene; Dipeptides; Luminescent Measurements; Neutrophils; Opsonin Proteins; Phagocytosis; Zymosan
PubMed: 640731
DOI: 10.1128/iai.19.3.833-838.1978 -
Infection and Immunity Sep 1980Previous analysis of soluble peptidoglycan (PG) fragments released by exponentially growing gonococci implicated the combined action of both hexosaminidase and amidase...
Previous analysis of soluble peptidoglycan (PG) fragments released by exponentially growing gonococci implicated the combined action of both hexosaminidase and amidase activities in PG turnover. Current studies further characterized PG fragments which were labeled in the glycan with D-glucosamine and in the peptide moiety with meso-diaminopimelic acid of L- and D-alanine. Labeled PG fragments were isolated by gel filtration and characterized on the bases of (i) KD values, (ii) free amino group analysis using fluorodinitrobenzene, (iii) borohydride reduction, (iv) alkali-catalyzed beta-elimination, (v) paper chromatography in various solvents, (vi) electrophoretic mobility at various pH values, (vii) digestibility by Charonia lampas glycosidases, and (viii) content of labeled D- and L-alanine. A set of well-characterized PG fragments was used as standards. The monomer fraction (the major extracellular product) was found to contain two components. Most (about 80%) appeared to be N-acetylglucosaminyl-beta-1 leads to 4-1,6-anhydro-N-acetylmuramyl-L-ala-D-glu-meso-diaminopimelic acid; the remainder was the corresponding disaccharide tetrapeptide containing a C-terminal D-alanine. An unusual feature of these products was the presence of the anhydro-muramyl (non-reducing) ends, reflecting the activity of a gonococcal transglycosylase, and the near absence of products containing detectable reducing ends. Otherwise, the structures of the monomer fragments were typical of those expected for a gram-negative bacterium (chemotype I). The corresponding peptide-cross-linked dimer and the free disaccharide also contained nonreducing ends, exclusively. Free peptides (products of amidase activity) consisted of both tripeptide and tetrapeptide. In summary, all gonococci examined appear to possess an unusual transglycosylase activity which contributes to the release of soluble PG fragments containing nonreducing, anhydro-muramyl ends. The release of these fragments in vivo might be a unique aspect of gonococci-host interactions.
Topics: Amino Acids; Dinitrofluorobenzene; Macromolecular Substances; Molecular Weight; Muramic Acids; Neisseria gonorrhoeae; Peptidoglycan; Radiochemistry; Solubility; Sugar Acids
PubMed: 6776063
DOI: 10.1128/iai.29.3.914-925.1980 -
Clinical and Experimental Immunology Jan 2009Inflammatory bowel disease (IBD) is the most common and serious chronic inflammatory condition of the gut. Among the distinct T helper (Th) cell subsets, a Th1 type... (Comparative Study)
Comparative Study
Inflammatory bowel disease (IBD) is the most common and serious chronic inflammatory condition of the gut. Among the distinct T helper (Th) cell subsets, a Th1 type response is associated predominantly with Crohn's disease (CD) while helminth infections generate a strong Th2 type response. IBD is most prevalent in developed countries but rare in countries where infections with helminths are common. Thus, it has been hypothesized that infection with helminth infection influence the development of CD and recent clinical and experimental studies suggest strongly a beneficial role of helminth infection in IBD. In the present study we examined the effects of rectal submucosal administration of helminth antigens on subsequent experimental colitis. Mice were treated with Trichinella spiralis antigens prior to the induction of dinitrobenzenesulphonic acid (DNBS)-induced colitis and were killed 3 days post-DNBS to assess colonic damage macroscopically, histologically and by myeloperoxidase (MPO) activity, inducible nitric oxide synthase (iNOS) and cytokine levels. Previous treatment with T. spiralis antigens reduced the severity of colitis significantly, as assessed macroscopically and histologically, and reduced the mortality rate. This benefit was correlated with a down-regulation of MPO activity, interleukin (IL)-1beta production and iNOS expression and an up-regulation of IL-13 and transforming growth factor-beta production in colon. These results clearly show a beneficial role of local treatment with helminth antigens for experimental colitis and prompt consideration of helminth antigen-based therapy for IBD instead of infection with live parasites.
Topics: Animals; Antigens, Helminth; Colitis; Colon; Dinitrofluorobenzene; Injections; Interleukin-13; Interleukin-1beta; Male; Mice; Mice, Inbred C57BL; Models, Animal; Nitric Oxide Synthase Type II; Peroxidase; Rectum; Transforming Growth Factor beta; Trichinella spiralis; Trichinellosis; Vaccination
PubMed: 19016806
DOI: 10.1111/j.1365-2249.2008.03805.x -
International Journal of Molecular... Sep 2020Caffeic acid (CA) is produced from a variety of plants and has diverse biological functions, including anti-inflammation activity. It has been recently demonstrated that...
Caffeic acid (CA) is produced from a variety of plants and has diverse biological functions, including anti-inflammation activity. It has been recently demonstrated that caffeoyl-prolyl-histidine amide (CA-PH), which is CA conjugated with proline-histidine dipeptide, relieves atopic dermatitis (AD)-like phenotypes in mouse. In this study, we investigated the molecular mechanism underlying CA-PH-mediated alleviation of AD-like phenotypes using cell line and AD mouse models. We confirmed that CA-PH suppresses AD-like phenotypes, such as increased epidermal thickening, infiltration of mast cells, and dysregulated gene expression of cytokines. CA-PH suppressed up-regulation of cytokine expression through inhibition of nuclear translocation of NF-κB. Using a CA-PH affinity pull-down assay, we found that CA-PH binds to Fyn. In silico molecular docking and enzyme kinetic studies revealed that CA-PH binds to the ATP binding site and inhibits Fyn competitively with ATP. CA-PH further suppressed spleen tyrosine kinase (SYK)/inhibitor of nuclear factor kappa B kinase (IKK)/inhibitor of nuclear factor kappa B (IκB) signaling, which is required for nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. In addition, chronic application of CA-PH, in contrast with that of glucocorticoids, did not induce up-regulation of regulated in development and DNA damage response 1 (REDD1), reduction of mammalian target of rapamycin (mTOR) signaling, or skin atrophy. Thus, our study suggests that CA-PH treatment may help to reduce skin inflammation via down-regulation of NF-κB activation, and Fyn may be a new therapeutic target of inflammatory skin diseases, such as AD.
Topics: Amides; Animals; Anti-Inflammatory Agents; Atrophy; Caffeic Acids; Dermatitis, Atopic; Dinitrofluorobenzene; Dipeptides; Disease Models, Animal; Female; Gene Expression Regulation; Glycoconjugates; HaCaT Cells; Humans; I-kappa B Kinase; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; NF-kappa B; Protein Binding; Proto-Oncogene Proteins c-fyn; Signal Transduction; Skin; Syk Kinase; TOR Serine-Threonine Kinases; Transcription Factors
PubMed: 32998341
DOI: 10.3390/ijms21197160 -
Proceedings of the National Academy of... Jan 2021Dysregulation of inflammatory cytokines in keratinocytes promote the pathogenesis of the skin inflammation, such as allergic contact dermatitis (ACD). High-mobility...
Dysregulation of inflammatory cytokines in keratinocytes promote the pathogenesis of the skin inflammation, such as allergic contact dermatitis (ACD). High-mobility group box 1 protein (HMGB1) has been implicated in the promotion of skin inflammation upon its extracellular release as a damage-associated molecular pattern molecule. However, whether and how HMGB1 in keratinocytes contributes to ACD and other skin disorders remain elusive. In this study, we generated conditional knockout mice in which the gene is specifically deleted in keratinocytes, and examined its role in ACD models. Interestingly, the mutant mice showed exacerbated skin inflammation, accompanied by increased ear thickening in 2,4-dinitrofluorobenezene-induced ACDs. The mRNA expression of interleukin-24 (IL-24), a cytokine known to critically contribute to ACD pathogenesis, was elevated in skin lesions of the mutant mice. As with constitutively expressed, IL-4-induced mRNA, expression was also augmented in the -deficient keratinocytes, which would account for the exacerbation of ACD in the mutant mice. Mechanistically, we observed an increased binding of trimethyl histone H3 (lys4) (H3K4me3), a hallmark of transcriptionally active genes, to the promoter region of the gene in the -deficient cells. Thus, the nuclear HMGB1 is a critical "gate keeper" in that the dermal homeostasis is contingent to its function in chromatin remodeling. Our study revealed a facet of nuclear HMGB1, namely its antiinflammatory function in keratinocytes for the skin homeostasis.
Topics: Animals; Chromatin Assembly and Disassembly; Dermatitis, Allergic Contact; Dinitrofluorobenzene; Disease Models, Animal; Ear; Gene Deletion; Gene Expression Regulation; HMGB1 Protein; Histones; Inflammation; Interleukin-4; Interleukins; Keratinocytes; Mice; Mice, Knockout; Promoter Regions, Genetic; Skin; Transplantation Chimera
PubMed: 33443188
DOI: 10.1073/pnas.2022343118