RESUMEN
BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease with an associated barrier dysfunction and Staphylococcus aureus infection. The mainstay steroid and calcineurin inhibitor therapy shows some adverse effects. 2,4-Dimethoxy-6-methylbenzene-1,3-diol (DMD) is a benzenoid isolated from Antrodia camphorata. OBJECTIVE: We investigated the inhibitory effect of DMD on methicillin-resistant S. aureus (MRSA), the chemokine production in stimulated keratinocytes, and the AD-like lesion found in ovalbumin (OVA)-sensitized mice. METHODS: The antimicrobial effect and cutaneous barrier function were evaluated using an in vitro culture model and an in vivo mouse model of AD-like skin. RESULTS: DMD exhibited a comparative minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against MRSA with nalidixic acid, a conventional antibiotic. The MIC and MBC for DMD was 78.1 and 156.3 µg/ml, respectively. DMD also showed the ability to eliminate the clinical bacteria isolates with resistance to methicillin and vancomycin. The DNA polymerase and gyrase inhibition evoked by DMD for bacterial lethality was proposed. In the activated keratinocytes, DMD stopped the upregulation of chemokines (CCL5 and CCL17) and increased the expression of differentiation proteins (filaggrin, involucrin, and integrin ß-1). Topical application of DMD facilely penetrated into the skin, with AD-like skin displaying 2.5-fold greater permeation than healthy skin. The in vivo assessment using the mouse model with OVA sensitization and MRSA inoculation revealed a reduction of transepidermal water loss (TEWL) and bacterial burden by DMD by about 2- and 100-fold, respectively. Differentiation proteins were also restored after topical DMD delivery. CONCLUSION: Our data demonstrated an advanced concept of AD treatment by combined barrier repair and bacterial eradication with a sole agent for ameliorating the overall complications.
Asunto(s)
Antibacterianos/farmacología , Antrodia/química , Dermatitis Atópica/tratamiento farmacológico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Tolueno/análogos & derivados , Tolueno/farmacología , Administración Cutánea , Animales , Antibacterianos/aislamiento & purificación , Antibacterianos/uso terapéutico , Línea Celular , Quimiocinas/inmunología , Quimiocinas/metabolismo , Dermatitis Atópica/inmunología , Dermatitis Atópica/microbiología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Proteínas Filagrina , Humanos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/metabolismo , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Ácido Nalidíxico/farmacología , Ácido Nalidíxico/uso terapéutico , Ovalbúmina/inmunología , Piel/efectos de los fármacos , Piel/inmunología , Piel/metabolismo , Piel/microbiología , Infecciones Cutáneas Estafilocócicas/inmunología , Infecciones Cutáneas Estafilocócicas/microbiología , Porcinos , Tolueno/aislamiento & purificación , Tolueno/uso terapéutico , Resultado del Tratamiento , Pérdida Insensible de Agua/efectos de los fármacosRESUMEN
Ultraviolet radiation (UVr) promotes several well-known molecular changes, which may ultimately impact on health. Some of these effects are detrimental, like inflammation, carcinogenesis and immunosuppression. On the other hand, UVr also promotes vitamin D synthesis and other beneficial effects. We recently demonstrated that exposure to very low doses of UVr on four consecutive days [repetitive low UVd (rlUVd)] does not promote an inflammatory state, nor the recruitment of neutrophils or lymphocytes, as the exposure to a single high UV dose (shUVd) does. Moreover, rlUVd reinforce the epithelium by increasing antimicrobial peptides transcription and epidermal thickness. The aim of this study was to evaluate the adaptive immune response after shUVd and rlUVd, determining T-cell and B-cell responses. Finally, we challenged animals exposed to both irradiation procedures with Staphylococcus aureus to study the overall effects of both innate and adaptive immunity during a cutaneous infection. We observed, as expected, a marked suppression of T-cell and B-cell responses after exposure to an shUVd but a novel and significant increase in both specific responses after exposure to rlUVd. However, the control of the cutaneous S. aureus infection was defective in this last group, suggesting that responses against pathogens cannot be ruled out from isolated stimuli.
Asunto(s)
Inmunidad Adaptativa/efectos de la radiación , Exposición a la Radiación , Rayos Ultravioleta , Animales , Formación de Anticuerpos/inmunología , Formación de Anticuerpos/efectos de la radiación , Linfocitos B/inmunología , Linfocitos B/metabolismo , Linfocitos B/efectos de la radiación , Biomarcadores , Citocinas/metabolismo , Dermatitis/inmunología , Dermatitis/metabolismo , Dermatitis/microbiología , Dermatitis/prevención & control , Modelos Animales de Enfermedad , Inmunización , Inmunofenotipificación , Masculino , Ratones , Dosis de Radiación , Infecciones Cutáneas Estafilocócicas/inmunología , Infecciones Cutáneas Estafilocócicas/microbiología , Infecciones Cutáneas Estafilocócicas/prevención & control , Staphylococcus aureus/inmunología , Staphylococcus aureus/efectos de la radiación , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/efectos de la radiación , Toxoide Tetánico/administración & dosificación , Toxoide Tetánico/inmunologíaRESUMEN
The "Western diet" is characterized by increased intake of saturated and omega-6 (n-6) fatty acids with a relative reduction in omega-3 (n-3) consumption. These fatty acids can directly and indirectly modulate the gut microbiome, resulting in altered host immunity. Omega-3 fatty acids can also directly modulate immunity through alterations in the phospholipid membranes of immune cells, inhibition of n-6 induced inflammation, down-regulation of inflammatory transcription factors, and by serving as pre-cursors to anti-inflammatory lipid mediators such as resolvins and protectins. We have previously shown that consumption by breeder mice of diets high in saturated and n-6 fatty acids have inflammatory and immune-modulating effects on offspring that are at least partially driven by vertical transmission of altered gut microbiota. To determine if parental diets high in n-3 fatty acids could also affect offspring microbiome and immunity, we fed breeding mice an n-3-rich diet with 40% calories from fat and measured immune outcomes in their offspring. We found offspring from mice fed diets high in n-3 had altered gut microbiomes and modestly enhanced anti-inflammatory IL-10 from both colonic and splenic tissue. Omega-3 pups were protected during peanut oral allergy challenge with small but measurable alterations in peanut-related serologies. However, n-3 pups displayed a tendency toward worsened responses during E. coli sepsis and had significantly worse outcomes during Staphylococcus aureus skin infection. Our results indicate excess parental n-3 fatty acid intake alters microbiome and immune response in offspring.
Asunto(s)
Ácidos Grasos Omega-3/administración & dosificación , Inmunidad Innata , Microbiota , Fenómenos Fisiologicos de la Nutrición Prenatal/inmunología , Animales , Bacteroidetes , Colon/inmunología , Colon/microbiología , Resistencia a la Enfermedad , Infecciones por Escherichia coli/inmunología , Femenino , Bacterias Gramnegativas , Bacterias Grampositivas , Lipopolisacáridos , Masculino , Staphylococcus aureus Resistente a Meticilina/inmunología , Ratones , Ratones Endogámicos BALB C , Embarazo , Sepsis/inmunología , Infecciones Cutáneas Estafilocócicas/inmunología , Infecciones Cutáneas Estafilocócicas/microbiologíaRESUMEN
BACKGROUND: Streptococcus pyogenes (S. pyogenes) causes various serious diseases including necrotizing fasciitis and streptococcal toxic shock syndrome. One serious problem observed recently with S. pyogenes therapy is attenuation of the antibiotic effect, especially penicillin treatment failure and macrolide resistance. Hainosankyuto, a traditional Japanese medicine based on ancient Chinese medicine, has been used for treatment of infectious purulent diseases in Japan. In this study, we investigated the protective and therapeutic efficacy of Hainosankyuto against S. pyogenes-skin infection. METHODOLOGY/PRINCIPAL FINDINGS: A broth microdilution method revealed that Hainosankyuto did not show a direct anti-bacterial effect against S. pyogenes. Force-feeding Hainosankyuto to infected mice for 4 consecutive days increased the survival rate and reduced the size of local skin lesions compared with mice fed PBS. Although we did not find the significant recovery of survival rate in Hainosankyuto administration only after S. pyogenes infection, the sizes of ulcer lesion were significant smaller after Hainosankyuto administration compared with mice fed PBS. No difference was observed in the anti-bacterial effect of Hainosankyuto between macrolide-susceptible and -resistant strains. Blood bactericidal assay showed that the survival rate of S. pyogenes using the blood from Hainosankyuto-treated mice was lower than that using the blood from untreated mice. We also found increased levels of IL-12, IFN-γ and a decreased level of TNF-α in the serum of S. pyogenes-infected mice treated with Hainosankyuto. Mouse peritoneal macrophage from Hainosankyuto-treated mice had significant phagocytic activity and increased mRNA levels of IL-12, IFN-γ and decreased mRNA level of TNF-α compared with control macrophage. CONCLUSIONS/SIGNIFICANCE: Hainosankyuto increased survival rate after S. pyogenes infection and up-regulated both blood bactericidal activity and macrophage phagocytic activity through modulation of inflammatory cytokines. Our data also suggest Hainosankyuto may be useful for the treatment of S. pyogenes infection more prophylactically than therapeutically.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Medicina Kampo , Infecciones Cutáneas Estafilocócicas/prevención & control , Streptococcus pyogenes/efectos de los fármacos , Animales , Actividad Bactericida de la Sangre/efectos de los fármacos , Citocinas/sangre , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Fagocitosis/efectos de los fármacos , Infecciones Cutáneas Estafilocócicas/genética , Infecciones Cutáneas Estafilocócicas/inmunología , Infecciones Cutáneas Estafilocócicas/microbiología , Streptococcus pyogenes/patogenicidadRESUMEN
Atopic dermatitis can be a challenging disease to treat, often having a chronic or relapsing course. For patients with moderate to severe disease, it can result in significant morbidity and affect quality of life of patients or families. Current treatment can be associated with side effects or patient and caregiver concerns about use. Recent advances in the understanding of barrier defects and innate and adaptive immune systemic abnormalities in atopic dermatitis have provided potential new targets for therapeutic intervention. These advances include antimicrobial peptides, antistaphylococcal toxin strategies, Th2 cytokine inhibitors, and modulation of pruritus at the neuromediator level.
Asunto(s)
Péptidos Catiónicos Antimicrobianos/uso terapéutico , Terapias Complementarias , Dermatitis Atópica/terapia , Desensibilización Inmunológica , Infecciones Cutáneas Estafilocócicas/terapia , Animales , Antiinflamatorios/uso terapéutico , Péptidos Catiónicos Antimicrobianos/síntesis química , Dermatitis Atópica/complicaciones , Dermatitis Atópica/inmunología , Dermatitis Atópica/fisiopatología , Antagonistas de los Receptores Histamínicos/uso terapéutico , Humanos , Receptores de Quimiocina/antagonistas & inhibidores , Infecciones Cutáneas Estafilocócicas/complicaciones , Infecciones Cutáneas Estafilocócicas/inmunología , Infecciones Cutáneas Estafilocócicas/fisiopatología , Balance Th1 - Th2/efectos de los fármacos , Terapias en InvestigaciónRESUMEN
To enhance the potential therapeutic efficacy of an antimicrobial peptide human beta-defensin 3, two fusion peptides, a bactericidal-immunomodulatory fusion peptide human beta-defensin 3-mannose-binding lectin and a bactericidal-bactericidal fusion peptide human beta-defensin 3-lysozyme were synthesized and the bactericidal activities in vitro and in vivo against methicillin-resistant Staphylococcus aureus N315 were demonstrated in this study. Peptide human beta-defensin 3-lysozyme showed the best bactericidal activity in vitro, but human beta-defensin 3-mannose-binding lectin showed a significant improvement in angiogenesis and tissue reconstruction. Our results illustrated that outstanding bactericidal activity in vitro is not essential in the development of antimicrobial peptides. Fusion strategy and immunomodulatory factors should be utilized in novel antimicrobial peptide development.
Asunto(s)
Factores Inmunológicos/uso terapéutico , Lectina de Unión a Manosa/uso terapéutico , Péptidos/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , beta-Defensinas/uso terapéutico , Secuencia de Aminoácidos , Animales , Humanos , Factores Inmunológicos/síntesis química , Factores Inmunológicos/química , Factores Inmunológicos/farmacología , Masculino , Lectina de Unión a Manosa/síntesis química , Lectina de Unión a Manosa/química , Lectina de Unión a Manosa/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Péptidos/síntesis química , Péptidos/química , Péptidos/farmacología , Proteínas Recombinantes de Fusión/farmacología , Infecciones Cutáneas Estafilocócicas/inmunología , Infecciones Cutáneas Estafilocócicas/microbiología , Resultado del Tratamiento , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , beta-Defensinas/síntesis química , beta-Defensinas/química , beta-Defensinas/farmacologíaRESUMEN
OBJECTIVE: Dermcidin (DCD)-derived peptide is an antimicrobial peptide produced by the sweat glands. However, the levels of DCD-derived peptide in sweat were decreased in patients with atopic eczema (AE). The effect of viewing a humorous video on the levels of DCD-derived peptide was studied. METHODS: Twenty patients with AE viewed an 87-min humorous video (Modern Times, featuring Charlie Chaplin). Just before and immediately after viewing, sweat was collected, and the levels of DCD-derived peptide and total protein in sweat were measured. RESULTS: Viewing a humorous video increased the levels of DCD-derived peptide without affecting the levels of total protein in sweat. CONCLUSION: Viewing a humorous video increased DCD-derived peptide in sweat of patients with AE, and thus, it may be helpful in the treatment of skin infection of AE.
Asunto(s)
Dermatitis Atópica/psicología , Películas Cinematográficas , Proteínas del Tejido Nervioso/metabolismo , Sudor/inmunología , Ingenio y Humor como Asunto/psicología , Adulto , Estudios Cruzados , Dermatitis Atópica/inmunología , Femenino , Humanos , Inmunocompetencia/inmunología , Risa/fisiología , Risoterapia , Masculino , Péptidos , Infecciones Cutáneas Estafilocócicas/inmunología , Infecciones Cutáneas Estafilocócicas/psicologíaRESUMEN
For the treatment of atopic dermatitis, a variety of therapies are used including folk medicine. At present, there is no single treatment which is effective to cure the symptoms of atopic dermatitis completely in all patients. We are drawing attention to the high isolation rate of Staphylococcus aureus when starting disinfectant treatment combined with topical steroid therapies for the purpose of killing S. aureus. As a result, we examined many patients in whom almost a complete remission was obtained even after short periods of therapy, though it had been difficult to obtain improvement by conventional treatments. In many patients, IgE values and reagin antibody titer decrease dramatically soon after starting treatment. As a disinfectant, 10% povidone-iodine solution was used. We investigated also the effect of iodine contained in the povidone-iodine solution on the thyroid gland.
Asunto(s)
Antiinfecciosos Locales/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Yodóforos/uso terapéutico , Povidona Yodada/uso terapéutico , Administración Tópica , Adolescente , Adulto , Antiinfecciosos Locales/administración & dosificación , Antiinflamatorios/uso terapéutico , Niño , Dermatitis Atópica/inmunología , Dermatitis Atópica/microbiología , Emolientes/uso terapéutico , Femenino , Glucocorticoides , Humanos , Inmunoglobulina E/análisis , Yodo/análisis , Yodóforos/administración & dosificación , Masculino , Medicina Tradicional , Resistencia a la Meticilina , Satisfacción del Paciente , Vaselina/uso terapéutico , Povidona Yodada/administración & dosificación , Reaginas/análisis , Inducción de Remisión , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/inmunología , Staphylococcus aureus/inmunología , Staphylococcus aureus/aislamiento & purificación , Encuestas y Cuestionarios , Glándula Tiroides/efectos de los fármacos , Tirotropina/análisis , Tiroxina/análisis , Triyodotironina/análisisAsunto(s)
Dermatosis del Pie/tratamiento farmacológico , Panax , Plantas Medicinales , Polisacáridos/administración & dosificación , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Adyuvantes Inmunológicos , Animales , Antiinflamatorios no Esteroideos , Extractos Celulares/administración & dosificación , Dermatosis del Pie/inmunología , Cobayas , Técnicas In Vitro , Inyecciones Intradérmicas , Macrófagos/inmunología , Ratones , Panax/citología , Fagocitosis/efectos de los fármacos , Fagocitosis/inmunología , Extractos Vegetales/administración & dosificación , Piel/inmunología , Piel/patología , Infecciones Cutáneas Estafilocócicas/inmunología , Staphylococcus aureus/inmunologíaRESUMEN
Examinations of 126 patients with staphylococcal pyodermas have helped detect a relationship between the total antibiotic sensitivity of staphylococci isolated from the involved skin and the patient's immunity status. The total antibiotic sensitivity of staphylococci in directly proportional to the blood level of T-lymphocytes, to the degree of their sensitization to staphylococcus in the leukocyte migration inhibition test, and to the value of IgM/IgG ratio. A new synthetic preparation of thymus, thymogen, had a modulating effect on the lymphocytes of pyoderma patients, manifesting by the increment of the total count of T-lymphocytes and T-helpers. A reduction of the total antibiotic resistance of the agent in foci of skin infection and normalization of the immunologic reactivity parameters were recorded in 23 patients with chronic pyodermas after a course of thymogen therapy. An effective method for the management of chronic pyoderma by a combination of thymogen with antibiotics is suggested.