RESUMEN
The pandemic condition coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can take asymptomatic, mild, moderate, and severe courses. COVID-19 affects primarily the respiratory airways leading to dry cough, fever, myalgia, headache, fatigue, and diarrhea and can end up in interstitial pneumonia and severe respiratory failure. Reports about the manifestation of various skin lesions and lesions of the vascular system in some subgroups of SARS-CoV-2-positive patients as such features outside the respiratory sphere, are rapidly emerging. Vesicular, urticarial, and maculopapular eruptions and livedo, necrosis, and other vasculitis forms have been reported most frequently in association with SARS-CoV-2 infection. In order to update information gained, we provide a systematic overview of the skin lesions described in COVID-19 patients, discuss potential causative factors, and describe differential diagnostic evaluations. Moreover, we summarize current knowledge about immunologic, clinical, and histologic features of virus- and drug-induced lesions of the skin and changes to the vascular system in order to transfer this knowledge to potential mechanisms induced by SARS-CoV-2.
Asunto(s)
COVID-19/complicaciones , SARS-CoV-2 , Enfermedades de la Piel/etiología , Enzima Convertidora de Angiotensina 2/análisis , COVID-19/inmunología , COVID-19/patología , COVID-19/transmisión , Femenino , Humanos , Masculino , Piel/patología , Enfermedades de la Piel/patologíaRESUMEN
Type I IFN production of plasmacytoid dendritic cells (pDCs) triggered by TLR-signaling is an essential part of antiviral responses and autoimmune reactions. Although it was well-documented that members of the cytokine signaling (SOCS) family regulate TLR-signaling, the mechanism of how SOCS proteins regulate TLR7-mediated type I IFN production has not been elucidated yet. In this article, we show that TLR7 activation in human pDCs induced the expression of SOCS1 and SOCS3. SOCS1 and SOCS3 strongly suppressed TLR7-mediated type I IFN production. Furthermore, we demonstrated that SOCS1- and SOCS3-bound IFN regulatory factor 7, a pivotal transcription factor of the TLR7 pathway, through the SH2 domain to promote its proteasomal degradation by lysine 48-linked polyubiquitination. Together, our results demonstrate that SOCS1/3-mediated degradation of IFN regulatory factor 7 directly regulates TLR7 signaling and type I IFN production in pDCs. This mechanism might be targeted by therapeutic approaches to either enhance type I IFN production in antiviral treatment or decrease type I IFN production in the treatment of autoimmune diseases.
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Células Dendríticas/metabolismo , Factor 7 Regulador del Interferón/metabolismo , Interferón-alfa/metabolismo , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Receptor Toll-Like 7/metabolismo , Células Cultivadas , Células HEK293 , Humanos , Leucocitos Mononucleares/metabolismo , Transducción de Señal/fisiologíaRESUMEN
Male subfertility has been associated with bacterial infections and chronic inflammation. In this context, several studies investigated cytokine levels in seminal plasma, whereas interleukin-6 (IL-6) appears to be crucial. However, little is known about its receptor, the IL-6R expression on human spermatozoa. Thus, the aim of the present study was to screen spermatozoa for IL-6R expression and to identify its localisation. Semen samples of 137 patients (median age 37.69, SD ± 7.82) with subfertility were analysed. Sperm analysis including determination of IL-6 was performed following the World Health Organization criteria. Also, flow cytometry was performed for sperm IL-6R expression. IL-6R+ cells were used for immunofluorescence staining to identify receptor localisation. The results showed positive staining for IL-6R in the midpiece of spermatozoa. Furthermore, a significant correlation between sperm IL-6R expression, seminal plasma IL-6 and total sperm count could be demonstrated, whereas a negative correlation was observed in sperm IL-6R expression and motility. However, no statistical significance could be observed between IL-6R expression, vitality and morphology. Moreover, incubation of spermatozoa with IL-6 led to a slight but significant decrease in motility after 24 hr. These data suggest that IL-6R expression may play a role in impaired sperm function during inflammation.
Asunto(s)
Infertilidad Masculina/metabolismo , Receptores de Interleucina-6/metabolismo , Espermatozoides/metabolismo , Adulto , Humanos , Masculino , Persona de Mediana EdadRESUMEN
FcεRII is a multifunctional low-affinity IgER that is involved in the pathogenesis of allergic, inflammatory, and neoplastic diseases. Although discrepancies in FcεRII-mediated functions are being increasingly recognized, the consequences of FcεRII activation are not completely understood. In this study, we evaluated the expression of FcεRII on human blood cells and found that it was primarily expressed on monocytes and B cells. Although IL-4 promoted expression of the FcεRIIb isoform on B cells and monocytes, the expression of the FcεRIIa isoform was not dependent on IL-4. Furthermore, FcεRII predominantly bound allergen-IgE complexes on B cells but not on monocytes. FcεRII-mediated allergen-IgE complex uptake by B cells directed Ags to MHC class II-rich compartments. FcεRII-bearing monocytes and B cells expressed high levels of the FcεRII sheddase a disintegrin and metalloproteinase 10, which implies that they are important sources of soluble FcεRII. Moreover, we identified that IgE immune complex stimulation of FcεRII activated intracellular tyrosine phosphorylation via Syk in B cells but not in monocytes. Importantly, FcεRII-mediated signaling by allergen-IgE immune complexes increased IFN-γ production in B cells of allergic patients during the build-up phase of allergen-specific immunotherapy. Together, our results demonstrate that FcεRII mediates cell type-dependent function in allergic reactions. In addition, the results identify a novel allergen-IgE complex/FcεRII/Syk/IFN-γ pathway in allergic responses and suggest that FcεRII may play a role in regulating allergic reactions via modulating IFN-γ production in B cells.
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Linfocitos B/inmunología , Activación de Linfocitos/inmunología , Monocitos/inmunología , Receptores de IgE/inmunología , Hipersensibilidad Respiratoria/inmunología , Adulto , Anciano , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Hipersensibilidad , Immunoblotting , Inmunoprecipitación , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Transducción de Señal/inmunologíaRESUMEN
Mastocytosis is a rare heterogeneous disease characterized by increase of mast cells (MCs) in different organs. Neurotrophins (NTs) have been shown to promote differentiation and survival of MCs, which in turn represent a major source of NTs. Thus, a contribution of NTs to mastocytosis seems highly conceivable but has not yet been investigated. We could demonstrate expression of high-affinity NT receptors tropomyosin-related kinase A (TrkA) for nerve growth factor (NGF)-ß, TrkB for brain-derived neurotrophic factor, and NT-4 and TrkC for NT-3 on skin MCs; and of TrkA and TrkC on intestinal MCs of patients with mastocytosis. Moreover, increased expression of NGF-ß; NT-3; TrkA, TrkB, and TrkC; and isoforms truncated TrkB-T1 and truncated TrkC were observed on skin MCs. Patients with mastocytosis featured elevated serum levels of NGF, NT-3, and NT-4. Levels of NGF-ß and NT-4 correlated with tryptase levels, suggesting a link between MC load and blood levels of NGF and NT-4. Migration of CD117+ progenitor cells from the blood was enhanced toward NGF-ß gradient in both mastocytosis and controls. Together with enhanced NT levels, the elevated expression of modified Trk receptors on skin and gut MCs might contribute to the pathophysiology of mastocytosis in autocrine and paracrine loops.
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Tracto Gastrointestinal/patología , Mastocitos/metabolismo , Mastocitosis/sangre , Mastocitosis/patología , Factores de Crecimiento Nervioso/sangre , Receptores de Factor de Crecimiento Nervioso/metabolismo , Piel/patología , Adolescente , Adulto , Anciano , Recuento de Células , Movimiento Celular , Niño , Dermis/patología , Femenino , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica , Humanos , Masculino , Mastocitos/patología , Mastocitosis/genética , Persona de Mediana Edad , Factores de Crecimiento Nervioso/genética , Isoformas de Proteínas/metabolismo , Proteínas Proto-Oncogénicas c-kit/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Factor de Crecimiento Nervioso/genética , Adulto JovenAsunto(s)
Andrógenos , Basófilos , Antiinflamatorios/farmacología , Liberación de Histamina , Humanos , Inmunoglobulina ERESUMEN
The responsiveness of DCs and their precursors to transforming growth factor beta1 (TGF-ß1) affects the nature of differentiating DC subsets, which are essential for the severity of atopic dermatitis (AD). To evaluate TGF-ß signaling in monocytes and monocyte-derived DCs of AD patients compared with that of controls, in vitro generated Langerhans cell (LC) like DCs, expression of TGF-ß receptors, phospho-Smad2/3 and Smad7 were evaluated. Furthermore, TNF-α expression and synergistic effects of TNF-α upon TGF-ß signaling and DC generation were evaluated. We found LC-like DC differentiation of monocytes from AD patients in response to TGF-ß1 was remarkably reduced and TGF-ß1 receptor expression was significantly lower compared with that of healthy controls. Attenuated TGF-ß1 responsiveness mirrored by lower phospho-Smad2/3 expression after TGF-ß1 stimulation and higher expression of inhibitory Smad7 was observed in monocytes from AD patients. During DC generation, mRNA expression of Smad7 was relatively higher in LC-like DCs of AD patients. Lower TNF-α expression of monocytes from AD patients might further contribute to attenuated TGF-ß signaling in the disease since TNF-α had synergistic effects on TGF-ß1 signaling and LC generation through mediating the degradation of Smad7. Our results demonstrate alleviated TGF-ß1 signaling together with the amount of soluble co-factors might direct the nature of differentiating DCs.
Asunto(s)
Dermatitis Atópica/inmunología , Regulación de la Expresión Génica/efectos de los fármacos , Células de Langerhans/inmunología , Monocitos/inmunología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Diferenciación Celular/inmunología , Células Cultivadas , Dermatitis Atópica/genética , Dermatitis Atópica/patología , Femenino , Regulación de la Expresión Génica/inmunología , Humanos , Células de Langerhans/efectos de los fármacos , Células de Langerhans/patología , Masculino , Persona de Mediana Edad , Monocitos/efectos de los fármacos , Monocitos/patología , Fosforilación/efectos de los fármacos , Receptores de Factores de Crecimiento Transformadores beta/genética , Receptores de Factores de Crecimiento Transformadores beta/inmunología , Transducción de Señal/efectos de los fármacos , Proteína Smad2/genética , Proteína Smad2/inmunología , Proteína smad3/genética , Proteína smad3/inmunología , Proteína smad7/genética , Proteína smad7/inmunología , Factor de Crecimiento Transformador beta1/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
An amphiphilic polymeric chelator (APC16-g-SX) grafted with sodium xanthate (SX) groups was successfully prepared for the efficient removal of high concentrations of Cu(II) from wastewater. The ordinary polymeric chelator (PAM-g-SX) based on linear polyacrylamide (PAM) was also prepared for comparative studies. The polymeric chelators were characterized by Fourier transform infrared spectroscopy (FT-IR), solid-state nuclear magnetic resonance (13C-NMR), gel permeation chromatography (GPC), elemental analyzer, and scanning electron microscope (SEM). The chelating performance of these polymeric chelators was investigated, and the mechanism of APC16-g-SX for enhanced removal of Cu(II) from wastewater was proposed based on fluorescence spectroscopy, cryo-scanning electron microscope (Cryo-SEM), energy-dispersive spectrometer (EDS), and X-ray photoelectron spectroscopy (XPS) tests. The results show that as the initial Cu(II) concentration in the wastewater increases, APC16-g-SX shows more excellent chelating performance than ordinary PAM-g-SX. For the wastewater with an initial Cu(II) concentration of 200 mg/L, the removal rate of Cu(II) was 99.82% and 89.34% for both 500 mg/L APC16-g-SX and PAM-g-SX, respectively. The pH of the system has a very great influence on the chelating performance of the polymeric chelators, and the increase in pH of the system helps to improve the chelating performance. The results of EDS and XPS tests also show that N, O, and S atoms in APC16-g-SX were involved in the chelation of Cu(II). The mechanism of enhanced removal of Cu(II) by APC16-g-SX can be attributed to the spatial network structure constructed by the self-association of hydrophobic groups that enhances the utilization of chelation sites.
Asunto(s)
Quelantes , Isópodos , Animales , Aguas Residuales , Espectroscopía Infrarroja por Transformada de Fourier , Cromatografía en Gel , PolímerosRESUMEN
Signals involved in the commitment of Th17 differentiation are of substantial interest for our understanding of antimicrobial defense mechanisms and autoimmune disorders. Various ways in which myeloid dendritic cells modulate Th17 differentiation have been identified. However, although plasmacytoid dendritic cells (PDCs) are regarded as important players in antiviral/antimicrobial host defense and autoimmune diseases, a putative modulatory role of PDCs in Th17 differentiation has not yet been elucidated in detail. We demonstrated that PDCs are capable of promoting Th17 differentiation in response to TLR7 stimulation. Further, both the differentiation of Th17 cells from naive T cells and the amplification of Th17 effector functions of memory T cells are promoted by PDCs after TLR7 activation. Our data are of strong clinical relevance because TLR7 activation in PDCs might represent one of the missing links between innate and adaptive immune mechanisms and contribute to the amplification of Th17-driven autoimmune disorders as well as viral host defense.
Asunto(s)
Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Interleucina-17/fisiología , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo , Receptor Toll-Like 7/metabolismo , Inmunidad Adaptativa , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/metabolismo , Diferenciación Celular/inmunología , Células Cultivadas , Técnicas de Cocultivo , Células Dendríticas/virología , Humanos , Inmunidad Innata , Memoria Inmunológica , Mediadores de Inflamación/metabolismo , Mediadores de Inflamación/fisiología , Gripe Humana/inmunología , Gripe Humana/metabolismo , Gripe Humana/virología , Interleucina-17/biosíntesis , Ligandos , Fase de Descanso del Ciclo Celular/inmunología , Linfocitos T Colaboradores-Inductores/citología , Linfocitos T Colaboradores-Inductores/virología , Receptor Toll-Like 7/fisiologíaRESUMEN
A porous scaffold/implant is considered a potential method to repair bone defects, but its mechanical stability and biomechanics during the repair process are not yet clear. A mandibular titanium implant was proposed and designed with layered porous structures similar to that of the bone tissue, both in structure and mechanical properties. Topology was used to optimize the design of the porous implant and fixed structure. The finite element analysis was combined with bone "Mechanostat" theory to evaluate the stress and osteogenic property of the layered porous implant with 3 different fixation layouts (Model I with 4 screws, Model II with 5 screws and Model III with 6 screws) for mandibular reconstruction. The results showed that Model III could effectively reduce the stress shielding effect, stress within the optimized implant, defective mandible, and screws were respectively dropped 48.18%, 44.23%, and 57.27% compared to Model I, and the porous implant had a significant stress transmission effect and maintained the same stress distribution as the intact mandible after the mandibular defect was repaired. The porous implant also showed a significant mechanical stimulation effect on the growth and healing of the bone tissue according to the bone "Mechanostat" theory. The combination of porous structure with the topology technique is a promising option to improve the mechanical stability and osteogenesis of the implant, and could provide a new solution for mandibular reconstruction.
Asunto(s)
Reconstrucción Mandibular , Fenómenos Biomecánicos , Análisis de Elementos Finitos , Mandíbula , Porosidad , Estrés Mecánico , TitanioRESUMEN
Allergens and microbial antigens impact on effector cells and antigen-presenting cells in allergic diseases. Allergens bind specifically to immunoglobulin E (IgE) linked to the high-affinity receptor for IgE (FcepsilonRI) and stimulate a cascade of cellular events. This leads to the release of mediators of allergic reactions by effector cells on the one hand and antigen uptake, presentation and T cell priming by antigen-presenting cells on the other hand. In contrast, microbial antigens are recognized by pattern-recognition receptors (PRRs) of the innate immune system, to which Toll-like receptors (TLRs) belong. In view of the high number of microbial antigens, allergens and other soluble ligands in the cellular microenvironment in vivo, it is very likely that not only separate, but also concomitant stimulation of both receptor types, i.e. FcepsilonRI and TLRs, occurs frequently under physiological conditions and in particular in the context of allergic and infectious disorders. Thus, interaction of TLRs with FcepsilonRI and regulation of the IgE synthesis is of critical immunological importance, since it might profoundly modify the activation state of cells and the nature of the evolving immune responses. Current knowledge about the cross talk of TLRs with FcepsilonRI- and IgE-related immune responses is discussed herein.
Asunto(s)
Linfocitos B/inmunología , Células Dendríticas/inmunología , Inmunoglobulina E/inmunología , Mastocitos/inmunología , Receptores de IgE/inmunología , Receptores Toll-Like/inmunología , Alérgenos/inmunología , Alérgenos/metabolismo , Alérgenos/uso terapéutico , Animales , Linfocitos B/metabolismo , Citocinas/inmunología , Citocinas/metabolismo , Células Dendríticas/metabolismo , Humanos , Hipersensibilidad/inmunología , Hipersensibilidad/metabolismo , Hipersensibilidad/terapia , Inmunidad Innata/inmunología , Inmunoglobulina E/metabolismo , Inmunoterapia , Mastocitos/metabolismo , Receptores de IgE/metabolismo , Receptores Toll-Like/metabolismoRESUMEN
Osteoarthritis (OA) is one of the most prevalent joint disorders globally. Patients suffering from OA are often obese and adiposity is linked to chronic inflammation. In the present study, the potential of using exosomes isolated from adiposederived stem cells (ADSCs) as a therapeutic tool for reducing chronic inflammation and promoting chondrogenesis was investigated using patientderived primary cells. First, it was tested whether patientderived ADSCs could differentiate into chondrogenic and osteogenic lineages. The ADSCs were then used as a source of exosomes. It was found that exosomes isolated from ADSCs, when cocultured with activated synovial fibroblasts, downregulated the expression of proinflammatory markers interleukin (IL)6, NFκB and tumor necrosis factorα, while they upregulated the expression of the antiinflammatory cytokine IL10; without exosomes, the opposite observations were made. In addition, inflammationinflicted oxidative stress was induced in vitro by stimulating chondrocytes with H2O2. Treatment with exosomes protected articular chondrocytes from H2O2induced apoptosis. Furthermore, exosome treatment promoted chondrogenesis in periosteal cells and increased chondrogenic markers, including Collagen type II and ßcatenin; inhibition of Wnt/ßcatenin, using the antagonist ICG001, prevented exosomeinduced chondrogenesis. Periosteal cells treated with exosomes exhibited higher levels of microRNA (miR)145 and miR221. The upregulation of miR145 and miR221 was associated with the enhanced proliferation of periosteal cells and chondrogenic potential, respectively. The present study provided evidence in support for the use of patientderived exosomes, produced from ADSCs, for potential chondrogenic regeneration and subsequent amelioration of osteoarthritis.
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Tejido Adiposo/citología , Condrogénesis , Exosomas/metabolismo , Inflamación/patología , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , Regulación hacia Arriba , Anciano , Diferenciación Celular , Movimiento Celular , Condrocitos/metabolismo , Fibroblastos/metabolismo , Humanos , Macrófagos/metabolismo , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Membrana Sinovial/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
BACKGROUND: The proportion of dendritic cell subpopulations in the skin is important for the severity of atopic dermatitis because topical treatment with tacrolimus leads to rapid depletion of inflammatory dendritic epidermal cells, whereas Langerhans cells (LCs) predominate in cured sites. OBJECTIVES: The effects of tacrolimus and TGF-beta1 on LC differentiation and the idea of tacrolimus skewing the differentiation of epidermal precursors to LCs were evaluated. METHODS: The presence of LC markers, MHC, and costimulatory molecules and stimulatory capacity toward T cells of monocyte-derived LCs were analyzed. Skin samples of patients with atopic dermatitis were assessed by means of immunofluorescence microscopy before and after tacrolimus treatment. TGF-beta production of skin cells was analyzed. RESULTS: Tacrolimus and TGF-beta1 act synergistically on the generation of LCs and the expression of CD40, CD80, CD86, CD83, and MHC II; stabilize TGF-beta receptor II expression; and decrease the stimulatory capacity of LCs toward T cells. In vivo the number of epidermal LCs in tacrolimus-treated skin increased. CONCLUSION: The synergism between TGF-beta1 and tacrolimus leads to the generation of LCs, reduced expression of costimulatory and MHC II molecules, and reduced stimulatory activity. Shifting the balance of the dendritic cell population to LCs might be of major importance for the therapeutic effect of tacrolimus.
Asunto(s)
Células Dendríticas/inmunología , Dermatitis Atópica/inmunología , Inmunosupresores/farmacología , Células de Langerhans/inmunología , Proteínas Serina-Treonina Quinasas/inmunología , Receptores de Factores de Crecimiento Transformadores beta/inmunología , Tacrolimus/farmacología , Factor de Crecimiento Transformador beta1/farmacología , Adulto , Diferenciación Celular , Citocinas/inmunología , Citocinas/metabolismo , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Sinergismo Farmacológico , Epidermis/inmunología , Femenino , Humanos , Células de Langerhans/citología , Células de Langerhans/efectos de los fármacos , Masculino , Receptor Tipo II de Factor de Crecimiento Transformador beta , Linfocitos T/inmunología , Factor de Crecimiento Transformador beta1/administración & dosificaciónRESUMEN
BACKGROUND: Despite high bacterial colonization, acute infections are rare in the oral mucosa, implicating tolerogenic predominance. Bacterial antigens like LPSs are recognized by innate immunity receptors such as Toll-like receptor 4 (TLR4), associated with LPS receptor (CD14). OBJECTIVES: Toll-like receptor 4 agonist monosphoryl lipid A has been successfully used as adjuvant in subcutaneous immunotherapy, suggesting reinforcement of allergen-specific tolerance. Recently sublingual immunotherapy (SLIT) has been shown to be an effective alternative to subcutaneous immunotherapy. We observed CD14 expression on human oral Langerhans cells (oLCs), representing a major target of SLIT. However, not much is known about TLR4 expression and its effect on oLCs. METHODS: Cell suspensions were obtained by trypsinization of human oral mucosa and analyzed by flow cytometry, RT-PCR, cytometric bead arrays, ELISA, and mixed lymphocyte reactions. RESULTS: We could show that oLCs express TLR4, and its ligation by monosphoryl lipid A upregulated expression of coinhibitory molecules B7-H1 and B7-H3 while surface expression of costimulatory molecule CD86 was concomitantly decreased. Furthermore, TLR4 ligation on oLCs increased their release of the anti-inflammatory cytokine IL-10 and decreased their stimulatory capacity toward T cells. Moreover, TLR4-ligation on oLCs induced IL-10, TGF-beta1, Forkhead box protein 3, IFN-gamma, and IL-2 production in T cells. CONCLUSION: In view of these data, TLR4-ligation on oLCs might not only play a role in pathogen recognition for efficient immunity but also contribute to the tolerogenic state predominating in the oral cavity.
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Adyuvantes Inmunológicos/farmacología , Tolerancia Inmunológica/efectos de los fármacos , Células de Langerhans/inmunología , Lípido A/análogos & derivados , Mucosa Bucal/inmunología , Receptor Toll-Like 4/antagonistas & inhibidores , Antígenos CD/metabolismo , Antígenos B7 , Antígeno B7-2/metabolismo , Antígeno B7-H1 , Citocinas/metabolismo , Regulación hacia Abajo , Factores de Transcripción Forkhead/metabolismo , Humanos , Técnicas In Vitro , Interleucina-10/metabolismo , Células de Langerhans/metabolismo , Lípido A/farmacología , Mucosa Bucal/metabolismo , Receptores Inmunológicos/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Células TH1/metabolismo , Receptor Toll-Like 4/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Regulación hacia ArribaRESUMEN
BACKGROUND: To compare the therapeutic effect of photodynamic therapy (PDT) with Toluidine blue O hydrogel versus systemic antibiotic (SA) in treating periodontitis on rats. METHODS: Thirty-two Wistar rats were divided into four groups and treated differently: Negative control (NC) group, normal rats; positive control (PC) group, rats with periodontitis; SA group, rats with periodontitis treated with systemic antibiotic; PDT group, rats with periodontitis treated with PDT. After treatment, gingival sulcus bacterial load was measured by counting the colony forming units per milliliter (CFU mL-1 ). The tooth and periodontal tissues were histologically processed to analyze histological and immunohistochemical profile. Gingival samples were obtained to quantify interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) levels. RESULTS: Gingival sulcus bacteria load is significantly lower in PDT group compared with the SA group. The histological analysis showed that some extremely effective repair signs of periodontal tissue were presented in PDT group, such as no periodontal pocket, no bone resorption, few inflammatory cells, massive fibroblasts and collagen fibers. Several effective repair signs of periodontal tissue were also observed in SA group, such as shallow periodontal pocket, small amount of inflammatory cells, substantial fibroblasts and collagen fibers. There were lower cyclooxygenase-2, matrix metalloproteinase -8 (MMP-8) and RANK immunolabeling, higher osteoprotegerin immunolabeling in PDT group compared with SA group. The IL-1ß and TNF-α levels in PDT group were lower than those in NC group, but higher than those in SA group. CONCLUSION: PDT was effective to treat experimental periodontitis and was superior to systemic metronidazole as a treatment for periodontitis.
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Periodontitis , Fotoquimioterapia , Animales , Antibacterianos , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfaRESUMEN
In maxillofacial surgery, there is a significant need for the design and fabrication of porous scaffolds with customizable bionic structures and mechanical properties suitable for bone tissue engineering. In this paper, we characterize the porous Ti6Al4V implant, which is one of the most promising and attractive biomedical applications due to the similarity of its modulus to human bones. We describe the mechanical properties of this implant, which we suggest is capable of providing important biological functions for bone tissue regeneration. We characterize a novel bionic design and fabrication process for porous implants. A design concept of "reducing dimensions and designing layer by layer" was used to construct layered slice and rod-connected mesh structure (LSRCMS) implants. Porous LSRCMS implants with different parameters and porosities were fabricated by selective laser melting (SLM). Printed samples were evaluated by microstructure characterization, specific mechanical properties were analyzed by mechanical tests, and finite element analysis was used to digitally calculate the stress characteristics of the LSRCMS under loading forces. Our results show that the samples fabricated by SLM had good structure printing quality with reasonable pore sizes. The porosity, pore size, and strut thickness of manufactured samples ranged from (60.95± 0.27)% to (81.23±0.32)%, (480±28) to (685±31) µm, and (263±28) to (265±28) µm, respectively. The compression results show that the Young's modulus and the yield strength ranged from (2.23±0.03) to (6.36±0.06) GPa and (21.36±0.42) to (122.85±3.85) MPa, respectively. We also show that the Young's modulus and yield strength of the LSRCMS samples can be predicted by the Gibson-Ashby model. Further, we prove the structural stability of our novel design by finite element analysis. Our results illustrate that our novel SLM-fabricated porous Ti6Al4V scaffolds based on an LSRCMS are a promising material for bone implants, and are potentially applicable to the field of bone defect repair.
Asunto(s)
Huesos/patología , Implantación de Prótesis Maxilofacial , Impresión Tridimensional , Diseño de Prótesis , Cirugía Bucal/instrumentación , Titanio/química , Aleaciones , Biónica , Sustitutos de Huesos/química , Huesos/metabolismo , Fuerza Compresiva , Módulo de Elasticidad , Análisis de Elementos Finitos , Humanos , Rayos Láser , Ensayo de Materiales , Porosidad , Presión , Prótesis e Implantes , Estrés Mecánico , Ingeniería de Tejidos/métodosRESUMEN
A subgroup of patients with atopic dermatitis develops one or more episodes of a severe viral skin infection caused by herpes simplex virus superimposed on eczematous skin lesions. This condition is named atopic dermatitis complicated by eczema herpeticum. Characteristic features of patients developing eczema herpeticum include an early age of onset of atopic dermatitis with a persistent and severe course into adulthood, predilection for eczematous skin lesions in the head and neck area, elevated total serum IgE levels and increased allergen sensitisation. Deficiencies at the level of both the innate and the adaptive immune system, which have been identified in atopic dermatitis, are much more pronounced in this subgroup. Predisposing cellular factors include a reduced number of plasmacytoid dendritic cells in the epidermis and a modified capacity of these cells to produce type I interferons after allergen challenge. In addition, lower levels of antimicrobial peptides in the skin of atopic dermatitis patients, resulting in part from a Th2-prone micromilieu, contribute to the lack of an effective defence against viral attack. In this review, we summarise the current knowledge of the molecular pathogenesis of eczema herpeticum.
Asunto(s)
Dermatitis Atópica/complicaciones , Erupción Variceliforme de Kaposi , Simplexvirus/patogenicidad , Antibacterianos/uso terapéutico , Péptidos Catiónicos Antimicrobianos/inmunología , Péptidos Catiónicos Antimicrobianos/metabolismo , Antivirales/uso terapéutico , Citocinas/inmunología , Citocinas/metabolismo , Dermatitis Atópica/inmunología , Dermatitis Atópica/virología , Susceptibilidad a Enfermedades , Humanos , Erupción Variceliforme de Kaposi/diagnóstico , Erupción Variceliforme de Kaposi/tratamiento farmacológico , Erupción Variceliforme de Kaposi/inmunología , Erupción Variceliforme de Kaposi/virología , Factores de Riesgo , Enfermedades Cutáneas Virales/etiología , beta-Defensinas/inmunología , beta-Defensinas/metabolismo , CatelicidinasRESUMEN
Recognition of nucleic acids by TLR9 expressed by human plasmacytoid dendritic cells (PDC) plays a key role in the defense against viral infections. Upon microbial pathogen stimulation, PDC secrete large amounts of type I interferon and arbitrate thereby both innate and adaptive immune mechanisms. Unmethylated CpG motifs, which are an integral part of bacterial or viral DNA, are used in vitro and in vivo to activate the TLR9 pathway, whereas inhibitory oligodeoxynucleotide (iODN) are capable of depressing TLR9 signaling. In this study we demonstrate that TTAGGG motifs containing iODN efficiently block the TLR9 signaling in terms of herpes simplex virus (HSV)-induced type I interferon production by PDC. However, iODN, as well as control ODN, still promote PDC maturation with upregulated expression of costimulatory molecules, major histocompatibility complex molecules, and other signs for PDC maturation. Furthermore, iODN and control ODN incubated PDC demonstrate increased T-cell stimulatory functions. Coculture experiments with autologous T cells indicate that iODN-treated PDC induce more CD4(+)CD25(+)Foxp3(+) T regulatory cells from naive CD4(+) T cells and preincubation of HSV-stimulated PDC with iODN upregulated T cells' IFN-gamma production. These data indicate that iODN, while blocking type I interferon production by PDC, modify PDC activation and maturation as well as T-cell priming and stimulation. Knowledge about the different functions of iODN on PDC elucidated might be crucial for immunotherapeutic strategies in which iODN motifs are used to prevent the interaction of CpG-DNA with TLR9 to calm down specific immunological responses, because our data indicate that iODN might not only have inhibitory functions but also be effective activators of immune cells.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Células Dendríticas/inmunología , Interferón Tipo I/biosíntesis , Oligodesoxirribonucleótidos/farmacología , Simplexvirus/inmunología , Receptor Toll-Like 9/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Comunicación Celular , Técnicas de Cocultivo , Células Dendríticas/metabolismo , Factores de Transcripción Forkhead/metabolismo , Humanos , Interferón Tipo I/antagonistas & inhibidores , Interferón Tipo I/inmunología , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Prueba de Cultivo Mixto de Linfocitos , Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Receptor Toll-Like 9/inmunologíaRESUMEN
Atopic dermatitis (AD) presents as a chronic relapsing skin disease with high prevalence in children. The typical distributed skin lesions make the clinical diagnosis of AD very simple and clear-cut in most of the cases. In contrast, the underlying mechanisms leading to the manifestation of AD are more than complex and consist of genetic components combined with various deficiencies on the level of innate and adaptive immune mechanisms. Challenged by this puzzle, scientific approaches of the last years have made considerable progress in gaining insights into the mechanisms, which cause AD. AD is a biphasic inflammatory skin disease characterized by an initial phase predominated by Th2 cytokines which switches into a second, more chronic Th1-dominated eczematous phase. Two different dendritic cell (DC) subtypes bearing the high-affinity receptor for IgE (FcepsilonRI) have been identified in the epidermal skin of AD patients: FcepsilonRIhigh Langerhans cells (LCs) and FcepsilonRIhigh inflammatory dendritic epidermal cells (IDECs). These two DC subtypes are believed to contribute distinctly to the biphasic nature and the outcome of T cell responses in AD. In contrast, plasmacytoid DCs, which play an important role in the defence against viral infections, have been shown to bear the high-affinity receptor for IgE too but are nearly absent from the epidermal skin lesions of AD patients. In light of recent developments, the picture emerges that different IgE-receptor bearing DC subtypes in the blood and skin of AD patients play a pivotal role in the complex network of DCs, which is highlighted in this review.