RESUMEN
BACKGROUND: Celastrol, a pentacyclic triterpenoid quinonemethide isolated from several spp. of Celastraceae family, exhibits anti-inflammatory activities in a variety of diseases including arthritis. PURPOSE: This study aims to investigate whether the inhibition of NLRP3 inflammasome is engaged in the anti-inflammatory activities of celastrol and delineate the underlying mechanism. METHODS: The influence of celastrol on NLRP3 inflammasome activation was firstly studied in lipopolysaccharide (LPS)-primed mouse bone marrow-derived macrophages (BMDMs) and phorbol 12-myristate 13-acetate (PMA)-primed THP-1 cells treated with nigericin. Reconstituted inflammasome was also established by co-transfecting NLRP3, ASC, pro-caspase-1 and pro-IL-1ß in HEK293T cells. The changes of inflammasome components including NLRP3, ASC, pro-caspase-1/caspase-1 and pro-IL-1ß/IL-1ß were examined by enzyme-linked immunosorbent assay (ELISA), western blotting and immunofluorescence. Furthermore, Propionibacterium acnes (P. acnes)/LPS-induced liver injury and monosodium urate (MSU)-induced gouty arthritis in mice were employed in vivo to validate the inhibitory effect of celastrol on NLRP3 inflammasome. RESULTS: Celastrol significantly suppressed the cleavage of pro-caspase-1 and pro-IL-1ß, while not affecting the protein expressions of NLRP3, ASC, pro-caspase-1 and pro-IL-1ß in THP-1 cells, BMDMs and HEK293T cells. Celastrol suppressed NLRP3 inflammasome activation and alleviated P. acnes/LPS-induced liver damage and MSU-induced gouty arthritis. Mechanism study revealed that celastrol could interdict K63 deubiquitination of NLRP3, which may concern interaction of celastrol and BRCA1/BRCA2-containing complex subunit 3 (BRCC3), and thereby prohibited the formation of NLRP3, ASC and pro-caspase-1 complex to block the generation of mature IL-1ß. CONCLUSION: Celastrol suppresses NLRP3 inflammasome activation in P. acnes/LPS-induced liver damage and MSU-induced gouty arthritis via inhibiting K63 deubiquitination of NLRP3, which presents a novel insight into inhibition of celastrol on NLRP3 inflammasome and provides more evidences for its application in the therapy of inflammation-related diseases.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Artritis Gotosa/tratamiento farmacológico , Hígado/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Triterpenos/farmacología , Animales , Artritis Gotosa/inducido químicamente , Artritis Gotosa/metabolismo , Células HEK293 , Humanos , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Lipopolisacáridos/toxicidad , Hígado/microbiología , Hígado/patología , Lisina/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Mutantes , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Triterpenos Pentacíclicos , Propionibacterium acnes/patogenicidad , Células THP-1 , Ubiquitinación/efectos de los fármacos , Ácido Úrico/toxicidadRESUMEN
Fulminant hepatic failure (FHF) is a clinical syndrome characterized by a sudden and severe impairment in liver function. However, the precise mechanism of immune dysregulation that is significant to FHF pathogenesis remains unclear. Enhancer of zeste homolog 2 (EZH2) has been implicated in inflammation as a regulator of immune cell function. In this study, we investigated the role of EZH2 in an animal model of human FHF induced by Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS). We demonstrated that EZH2 depletion in dendritic cells (DCs) and pharmacological inhibition of EZH2 using GSK126 both significantly ameliorated liver injury and improved the survival rates of mice with P. acnes plus LPS-induced FHF, which could be attributed to the decreased infiltration and activation of CD4+ T cells in the liver, inhibition of T helper 1 cells and induction of regulatory T cells. The expression of EZH2 in DCs was increased after P. acnes administration, and EZH2 deficiency in DCs suppressed DC maturation and prevented DCs from efficiently stimulating CD4+ T-cell proliferation. Further mechanistic analyses indicated that EZH2 deficiency directly increased the expression of the transcription factor RUNX1 and thereby suppressed the immune functions of DCs. The functional dependence of EZH2 on RUNX1 was further illustrated in DC-specific Ezh2-deficient mice. Taken together, our findings establish that EZH2 exhibits anti-inflammatory effects through inhibition of RUNX1 to regulate DC functions and that inhibition of EZH2 alleviates P. acnes plus LPS-induced FHF, probably by inhibiting DC-induced adaptive immune responses. These results highlight the effect of EZH2 on DCs, serving as a guide for the development of a promising immunotherapeutic strategy for FHF.
Asunto(s)
Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Células Dendríticas/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Fallo Hepático Agudo/inducido químicamente , Propionibacterium acnes/patogenicidad , Animales , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/patología , Femenino , Humanos , Fallo Hepático Agudo/genética , RatonesRESUMEN
One new dibenzocycloheptene, validinol (1), and one butanolide firstly isolated from the natural source, validinolide (2), together with 17 known compounds were isolated from the stem of Cinnamomum validinerve. Among the isolates, lincomolide A (3), secosubamolide (7), and cinnamtannin B1 (19) exhibited potent inhibition on both superoxide anion generation (IC50 values of 2.98 ± 0.3 µM, 4.37 ± 0.38 µM, and 2.20 ± 0.3 µM, respectively) and elastase release (IC50 values of 3.96 ± 0.31 µM, 3.04 ± 0.23 µM, and 4.64 ± 0.71 µM, respectively) by human neutrophils. In addition, isophilippinolide A (6), secosubamolide (7), and cinnamtannin B1 (19) showed bacteriostatic effects against Propionibacterium acnes in in vitro study, with minimal inhibitory concentration (MIC) values at 16 µg/mL, 16 µg/mL, and 500 µg/mL, respectively. Further investigations using the in vivo ear P. acnes infection model showed that the intraperitoneal administration of the major component cinnamtannin B1 (19) reduced immune cell infiltration and pro-inflammatory cytokines TNF-α and IL-6 at the infection sites. The results demonstrated the potential of cinnamtannin B1 (19) for acne therapy. In summary, these results demonstrated the anti-inflammatory potentials of Formosan C. validinerve during bacterial infections.
Asunto(s)
Acné Vulgar/tratamiento farmacológico , Cinnamomum/química , Inflamación/tratamiento farmacológico , Extractos Vegetales/farmacología , Acné Vulgar/microbiología , Acné Vulgar/patología , Antibacterianos/química , Antibacterianos/farmacología , Humanos , Inflamación/metabolismo , Inflamación/microbiología , Inflamación/patología , Pruebas de Sensibilidad Microbiana , Monocitos/efectos de los fármacos , Monocitos/microbiología , Extractos Vegetales/química , Tallos de la Planta/química , Propionibacterium acnes/efectos de los fármacos , Propionibacterium acnes/patogenicidadRESUMEN
BACKGROUND: Propionibacterium acnes (P. acnes) is a novel pathogenic factor that contributes to cartilaginous endplate (CEP) degeneration. However, the underlying mechanism of P. acnes-induced CEP degeneration remains unclear. The objective of this study is to investigate the underlying mechanism of P. acnes-induced CEP degeneration. METHODS: We first examined MIF expression in degenerated human CEP samples by immunohistochemistry. We developed a P. acnes-induced rat model and detected MIF expression using immunohistochemistry. Additionally, we investigated the mechanism of P. acnes-induced CEP degeneration in CEP cells using western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: We found that compared with the normal human CEP, the expression of MIF was increased in the degenerated human CEP. In a rat model, P. acnes induced CEP degeneration and upregulated MIF expression significantly. More importantly, we revealed the underlying mechanism of P. acnes-induced CEP degeneration in the rat CEP cells. Firstly, P. acnes induced the expression of MIF in a concentration-dependent manner. Then, MIF upregulated the expression of MMP-13 and promoted the secretion of IL-6 and IL-1ß. Finally, P. acnes may promote MIF expression via NF-κB pathway rather than ERK1/2 pathway. CONCLUSION: P. acnes-induced MIF expression via NF-κB pathway may be the underlying mechanism of CEP degeneration.
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Cartílago Hialino/patología , Degeneración del Disco Intervertebral/metabolismo , FN-kappa B/fisiología , Propionibacterium acnes/patogenicidad , Adulto , Anciano , Animales , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Femenino , Humanos , Cartílago Hialino/metabolismo , Degeneración del Disco Intervertebral/etiología , Degeneración del Disco Intervertebral/patología , Oxidorreductasas Intramoleculares/metabolismo , Vértebras Lumbares , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Masculino , Metaloproteinasa 13 de la Matriz/metabolismo , Persona de Mediana Edad , Ratas , Ratas Sprague-Dawley , Adulto JovenRESUMEN
Acne, also known as acne vulgaris, is a common disorder of human skin involving the sebaceous gland and Propionibacterium acnes (P. acnes). Although there are a number of treatments suggested for acne, many of them have limitations in their safety and have efficacy issues. Therefore, there is a high demand to develop safe and effective novel acne treatments. In the present study, we demonstrate the protective effects of Rosa davurica Pall. leaves (RDL) extract against P. acnes-induced inflammatory responses in vitro and in vivo. The results showed that RDL dose-dependently inhibited the growth of skin bacteria, including P. acnes (KCTC3314) and aerobic Staphylococcus aureus (KCTC1621) or Staphylococcus epidermidis (KCTC1917). The downregulation of proinflammatory cytokines by RDL appears to be mediated by blocking the phosphorylations of mitogen-activated protein kinase (MAPK) and subsequent nuclear factor-kappa B (NF-κB) pathways in P. acnes-stimulated HaCaT cells. In a mouse model of acne vulgaris, histopathological changes were examined in the P. acnes-induced mouse ear edema. The concomitant intradermal injection of RDL resulted in the reduction of ear swelling in mice along with microabscess but exerted no cytotoxic effects for skin cells. Instrumental analysis demonstrated there were seven major components in the RDL extract, and they seemed to have important roles in the anti-inflammatory and antimicrobial effects of RDL. Conclusively, our present work showed for the first time that RDL has anti-inflammatory and antimicrobial effects against P. acnes, suggesting RDL as a promising novel strategy for the treatment of acne, including natural additives in anti-acne cosmetics or pharmaceutical products.
Asunto(s)
Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Edema/inmunología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/inmunología , Propionibacterium acnes/patogenicidad , Rosa/química , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Edema/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Propionibacterium acnes/inmunologíaRESUMEN
The microbiome represents a vast resource for drug discovery, as its members engage in constant conflict to outcompete one another by deploying diverse strategies for survival. Cutibacterium acnes is one of the most common bacterial species on human skin and can promote the common disease acne vulgaris. By employing a combined strategy of functional screening, genetics, and proteomics we discovered a strain of Staphylococcus capitis (S. capitis E12) that selectively inhibited growth of C. acnes with potency greater than antibiotics commonly used in the treatment of acne. Antimicrobial peptides secreted from S. capitis E12 were identified as four distinct phenol-soluble modulins acting synergistically. These peptides were not toxic to human keratinocytes and the S. capitis extract did not kill other commensal skin bacteria but was effective against C. acnes on pig skin and on mice. Overall, these data show how a member of the human skin microbiome can be useful as a biotherapy for acne vulgaris.
Asunto(s)
Acné Vulgar/terapia , Terapia Biológica/métodos , Piel/microbiología , Staphylococcus capitis/inmunología , Simbiosis/inmunología , Acné Vulgar/inmunología , Acné Vulgar/microbiología , Adulto , Animales , Femenino , Humanos , Queratinocitos/inmunología , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Proteínas Citotóxicas Formadoras de Poros/aislamiento & purificación , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Proteínas Citotóxicas Formadoras de Poros/toxicidad , Cultivo Primario de Células , Propionibacterium acnes/inmunología , Propionibacterium acnes/patogenicidad , Piel/inmunología , Staphylococcus capitis/aislamiento & purificación , Staphylococcus capitis/metabolismo , Porcinos , Pruebas de Toxicidad , Adulto JovenRESUMEN
Ozenoxacin is a topical quinolone showing potent antimicrobial activities against Gram-negative and Gram-positive bacteria and is widely used for the treatment of inflammatory acne. However, the anti-inflammatory activities of ozenoxacin have not been examined so far. In the present study, we investigated the in vitro and in vivo anti-inflammatory effects of ozenoxacin. The production of interleukin (IL)-6 and IL-8 by human epidermal keratinocytes stimulated by heat-killed Cutibacterium acnes was significantly inhibited by ozenoxacin at concentrations from 1 to 30 µg ml-1. Likewise, the production of IL-6, IL-8, and tumor necrosis factor alpha by stimulated THP-1 cells, a human monocyte cell line, was inhibited by ozenoxacin at concentrations from 1 to 30 µg ml-1. The production of IL-1ß by THP-1 was also inhibited by ozenoxacin at the concentration of 30 µg ml-1. Phosphorylation of the mitogen-activated protein kinases and degradation of IκB-α, an inhibitory factor of NF-κB in keratinocytes and THP-1 cells, was increased by stimulation with heat-killed C. acnes. Of these activated intracellular pathways, the p38 phosphorylation pathway was remarkably reduced by ozenoxacin in both keratinocytes and THP-1 cells. In addition, the application of 2% ozenoxacin suppressed the increase in the ear thickness of rats induced by an intracutaneous injection of heat-killed C. acnes. These findings suggest that ozenoxacin possesses an anti-inflammatory activity, which may contribute to its therapeutic effects on inflammatory acne.
Asunto(s)
Aminopiridinas/farmacología , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Quinolonas/farmacología , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/patología , Aminopiridinas/administración & dosificación , Animales , Antiinflamatorios/administración & dosificación , Línea Celular , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Humanos , Inflamación/microbiología , Inflamación/patología , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Propionibacterium acnes/patogenicidad , Quinolonas/administración & dosificación , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The Cutibacterium acnes (also called Propionibacterium acnes, P. acnes)-induced proliferation and migration of keratinocytes contribute to acne vulgaris (AV), which is a common inflammatory skin disease that causes physical and psychological impairments. Piceatannol (3, 5, 3', 4'-tetrahydroxy-trans-stilbene, PCT) is naturally present in many human diets and plays antioxidant and anti-inflammatory roles that inhibit cell proliferation and migration. We aimed to analyse the functions and underlying mechanisms of PCT in P. acnes-stimulated keratinocytes. First, PCT showed no toxicity against the normal human keratinocyte cell line HaCaT but inhibited P. acnes-induced HaCaT cell proliferation. Next, PCT promoted the nuclear translocation and target gene transcription of the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), thereafter decreasing intracellular reactive oxygen species (ROS) levels. In addition, PCT inhibited the nuclear translocation of p65 [a subunit of nuclear factor kappa B (NF-κB)] and the secretion of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interleukin-8 (IL-8). Finally, a transfection assay showed that PCT inhibited P. acnes-induced HaCaT cell proliferation and migration by activating the antioxidant Nrf2 pathway and inhibiting the inflammatory NF-κB pathway. Our data suggested that PCT alleviated P. acnes-induced HaCaT cell proliferation and migration through its antioxidant and anti-inflammatory roles, suggesting the potential of PCT to treat AV.
Asunto(s)
Acné Vulgar/prevención & control , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Queratinocitos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Piel/efectos de los fármacos , Estilbenos/farmacología , Acné Vulgar/metabolismo , Acné Vulgar/microbiología , Acné Vulgar/patología , Línea Celular , Interacciones Huésped-Patógeno , Humanos , Queratinocitos/metabolismo , Queratinocitos/microbiología , Queratinocitos/patología , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Propionibacterium acnes/patogenicidad , Transducción de Señal , Piel/metabolismo , Piel/microbiología , Piel/patología , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/metabolismoRESUMEN
Acne is a common skin affliction that involves excess sebum production and modified lipid composition, duct blockage, colonization by bacteria, and inflammation. Acne drugs target one or more of these steps, with antibiotics commonly used to treat the microbial infection for moderate to severe cases. Whilst a number of other acne therapies are purported to possess antimicrobial activity, this has been poorly documented in many cases. We conducted a comparative analysis of the activity of common topical acne drugs against the principal etiological agent associated with acne: the aerotolerant anaerobic Gram-positive organism Propionibacterium acnes (recently renamed as Cutibacterium acnes). We also assessed their impact on other bacteria that could also be affected by topical treatments, including both antibiotic-sensitive and antibiotic-resistant strains, using broth microdilution assay conditions. Drugs designated specifically as antibiotics had the greatest potency, but lost activity against resistant strains. The non-antibiotic acne agents did possess widespread antimicrobial activity, including against resistant strains, but at substantially higher concentrations. Hence, the antimicrobial activity of non-antibiotic acne agents may provide protection against a background of increased drug-resistant bacteria.
Asunto(s)
Acné Vulgar/tratamiento farmacológico , Antibacterianos/farmacología , Fármacos Dermatológicos/farmacología , Microbiota/efectos de los fármacos , Piel/microbiología , Acné Vulgar/microbiología , Administración Cutánea , Antibacterianos/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Farmacorresistencia Bacteriana , Humanos , Pruebas de Sensibilidad Microbiana , Propionibacterium acnes/efectos de los fármacos , Propionibacterium acnes/patogenicidadRESUMEN
Imbalance in skin microflora, particularly related to certain Cutibacterium acnes strains, may trigger acne. Application of non-acne-causing strains to the skin may modulate the skin microbiome and thereby lead to a reduction in acne. This pilot study evaluates the safety and efficacy of microbiome modulation on acne-prone skin. The study had 2 phases: active induction (5% benzoyl peroxide gel, 7 days) and interventional C. acnes strains treatment (5 weeks). Patients were randomized to either topical skin formulations PT1 (2 strains of C. acnes Single Locus Sequence Typing [SLST] type C3 and K8, 50% each) or PT2 (4 strains of C. acnes SLST type C3 [55%], K8 [5%], A5 [30%] and F4 [10%]). Safety and efficacy was evaluated in 14 patients (PT1=8/14, PT2=6/14). Skin microbiome composition shifted towards study formulations. No untoward adverse events, visible irritation, or significant flare-up were observed. Non-inflamed lesions and skin pH were reduced. Comedone counts improved clinically with no deterioration in inflammatory lesions.
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Acné Vulgar/tratamiento farmacológico , Peróxido de Benzoílo/uso terapéutico , Microbiota/efectos de los fármacos , Seguridad del Paciente , Propionibacteriaceae/patogenicidad , Propionibacterium acnes/patogenicidad , Acné Vulgar/microbiología , Acné Vulgar/terapia , Administración Tópica , Adolescente , Femenino , Humanos , Masculino , Proyectos Piloto , Pronóstico , Piel/microbiología , Factores de Tiempo , Transformación Bacteriana , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The role of skin microbiota in acne remains to be fully elucidated. Initial culture-based investigations were hampered by growth rate and selective media bias. Even with less biased genomic methods, sampling, lysis and methodology, the task of describing acne pathophysiology remains challenging. Acne occurs in sites dominated by Cutibacterium acnes (formerly Propionibacterium acnes) and Malassezia species, both of which can function either as commensal or pathogen. OBJECTIVES: This article aims to review the current state of the art of the microbiome and acne. METHODS: The literature regarding the microbiome and acne was reviewed. RESULTS: It remains unclear whether there is a quantitative difference in microbial community distribution, making it challenging to understand any community shift from commensal to pathogenic nature. It is plausible that acne involves (i) change in the distribution of species/strains, (ii) stable distribution with pathogenic alteration in response to internal (intermicrobe) or external stimuli (host physiology or environmental) or (iii) a combination of these factors. CONCLUSIONS: Understanding physiological changes in bacterial species and strains will be required to define their specific roles, and identify any potential intervention points, in acne pathogenesis and treatment. It will also be necessary to determine whether any fungal species are involved, and establish whether they play a significant role. Further investigation using robust, modern analytic tools in longitudinal studies with a large number of participants, may make it possible to determine whether the microbiota plays a causal role, is primarily involved in exacerbation, or is merely a bystander. It is likely that the final outcome will show that acne is the result of complex microbe-microbe and community-host interplay.
Asunto(s)
Acné Vulgar/etiología , Malassezia/inmunología , Microbiota/inmunología , Propionibacterium acnes/inmunología , Piel/microbiología , Humanos , Malassezia/patogenicidad , Propionibacterium acnes/patogenicidad , Piel/inmunología , Simbiosis/inmunologíaRESUMEN
Genomic studies revealed the existence of health- and acne-associated P. acnes strains and suggested novel approaches for broadening understanding of acne vulgaris. However, clinical association of P. acnes with disease or health has yet to be corroborated experimentally. Current animal models of acne do not closely mimic human disease and have unclear translational value. We have developed a murine model of acne by combining P. acnes inoculation with topical application of a synthetic human sebum. We showed that human sebum promoted persistence of intradermally injected P. acnes with little loss of viability after 1 week and permitted use of more physiologic inoculums. Application of acne-associated P. acnes RT4/5 strains led to development of moderate to severe skin pathology compared with application of health-associated type II P. acnes strains (RT2/6). RT4/5 P. acnes strains uniformly induced higher levels of KC (IL-8), IL-1α, IL-1ß, and IL-6 in vitro and in vivo compared with type II P. acnes strains. Overall, our data provide immunopathologic corroboration of health and disease association of clinical P. acnes strains and inform on a platform to query putative virulence factors uncovered by genomic studies.
Asunto(s)
Acné Vulgar/inmunología , Acné Vulgar/microbiología , Infecciones por Bacterias Grampositivas/inmunología , Propionibacterium acnes/inmunología , Piel/inmunología , Piel/patología , Acné Vulgar/genética , Acné Vulgar/patología , Animales , Células de la Médula Ósea , Línea Celular , Modelos Animales de Enfermedad , Femenino , Humanos , Interleucina-1alfa/metabolismo , Interleucina-6 , Interleucina-8/metabolismo , Ratones , Ratones Endogámicos C57BL , Propionibacterium acnes/patogenicidad , Piel/microbiología , Factores de VirulenciaRESUMEN
Although numerous recent studies have reported the development of sarcoidosis in patients treated with tumor necrosis factor alpha (TNF-α) inhibitors, it is unclear whether the pathogenesis of drug-induced sarcoidosis is identical to that of spontaneous sarcoidosis. We herein present the case of a patient who developed sarcoidosis 6 months after the introduction of etanercept as treatment for rheumatoid arthritis. Typical clinical symptoms with noncaseating epithelioid granulomas detected in a mediastinal lymph node specimen were consistent with the diagnosis of sarcoidosis. Immunohistochemistry revealed Propionibacterium acnes in the noncaseating granulomas. The present findings suggest that Propionibacterium acnes is a cause of sarcoidosis, even when the disease is induced by TNF-α inhibitors.
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Antiasmáticos/efectos adversos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Etanercept/efectos adversos , Etanercept/uso terapéutico , Propionibacterium acnes/patogenicidad , Sarcoidosis/inducido químicamente , Factor de Necrosis Tumoral alfa/efectos adversos , Antiasmáticos/uso terapéutico , Femenino , Granuloma/patología , Humanos , Ganglios Linfáticos/patología , Masculino , Mediastino/patología , Persona de Mediana EdadRESUMEN
Sarcoidosis is a systemic granulomatous disease that is most commonly manifested in the pulmonary system. Though the entire etiology of sarcoidosis remains unknown, it has been reported that Propionibacterium acnes (P. acnes) has been isolated from sarcoid lesions. Herein, we report a case of salpingitis arising from sarcoidosis. A female patient aged 37 years, gravida 2 para 0, who had been diagnosed with sarcoidosis at the age of 36 years, underwent laparoscopic right salpingectomy due to obvious right hydrosalpinx with recurrent refractory right lower abdominal pain. The pathological diagnosis was granulomatous salpingitis of the right fallopian tube suspecting sarcoidosis. Immunocytochemistry using a specific monoclonal antibody against P. acnes lipoteichoic acid (PAB antibody) revealed PAB-positive reaction in sarcoid granuloma. This is the first case of sarcoidosis that the presence of P. acnes was shown in sarcoid lesions in the fallopian tube.
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Infecciones por Bacterias Grampositivas/complicaciones , Complicaciones Infecciosas del Embarazo , Propionibacterium acnes/patogenicidad , Salpingitis , Sarcoidosis/complicaciones , Adulto , Femenino , Humanos , Laparoscopía , Embarazo , Complicaciones Infecciosas del Embarazo/etiología , Complicaciones Infecciosas del Embarazo/microbiología , Complicaciones Infecciosas del Embarazo/cirugía , Salpingectomía , Salpingitis/etiología , Salpingitis/microbiología , Salpingitis/cirugíaRESUMEN
INTRODUCTION: The purpose of this study was to further evaluate the pathogenicity of hemolytic and nonhemolytic phenotypes of Propionibacterium acnes (P acnes) isolates from shoulders of orthopaedic patients. METHODS: Thirty-one patient records were reviewed, which had a positive P acnes shoulder culture from joint aspiration fluid and/or intraoperative tissues for demographics, clinical course, culture, and laboratory data. Patients were categorized as definite infection, probable infection, or probable contaminant. Antibiotic resistance patterns and hemolysis characteristics were subsequently analyzed. RESULTS: Hemolysis demonstrated 100% specificity with a positive predictive value of 100% and 80% sensitivity with a negative predictive value of 73% for determining definite and probable infections. Hundred percent of the patients in the hemolytic group and only 27% of patients in the nonhemolytic group were classified as infected. Presenting inflammatory markers were markedly higher in the hemolytic group. Clindamycin resistance was found in 31% of the hemolytic strains, whereas no antibiotic resistance was observed in the nonhemolytic group. CONCLUSION: Hemolytic strains of P acnes exhibit enhanced pathogenicity to their host by eliciting a more prominent systemic inflammatory response, increased antibiotic resistance, and a more challenging clinical course. Hemolysis may serve as a specific marker for assisting in diagnosing true infection with P acnes. LEVEL OF EVIDENCE: Level III retrospective comparative study.
Asunto(s)
Artritis Infecciosa/diagnóstico , Artritis Infecciosa/microbiología , Artroplastía de Reemplazo de Hombro , Infecciones por Bacterias Grampositivas , Hemólisis , Propionibacterium acnes/patogenicidad , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/microbiología , Articulación del Hombro/microbiología , Articulación del Hombro/cirugía , Anciano , Antibacterianos/farmacología , Clindamicina/farmacología , Farmacorresistencia Bacteriana , Femenino , Humanos , Masculino , Propionibacterium acnes/efectos de los fármacos , Propionibacterium acnes/aislamiento & purificación , Estudios RetrospectivosRESUMEN
BACKGROUND: The existence of latent low-virulence anaerobic bacteria in degenerated intervertebral discs (IVDs) remains controversial. In this study, the prevalence of low-virulence anaerobic bacteria in degenerated IVDs was examined, and the correlation between bacterial infection and clinical symptoms was analysed. METHODS: Eighty patients with disc herniation who underwent discectomy were included in this study. Under a stringent protocol to ensure sterile conditions, 80 disc samples were intraoperatively retrieved and subjected to microbiological culture. Meanwhile, tissue samples from the surrounding muscle and ligaments were harvested and cultured as contamination markers. The severity of IVD degeneration and the prevalence of Modic changes (MCs) were assessed according to preoperative MRI analysis. RESULTS: Of the 80 cultured discs, 54 were sterile, and 26 showed the presence of bacteria: Propionibacterium acnes (21 cases) and coagulase-negative staphylococci (5 cases). MRI revealed that the presence of bacteria was significantly associated with MCs (P<0.001). However, there was no significant association between bacterial infection and the severity of IVD degeneration (P = 0.162). CONCLUSIONS: Our findings further validated the presence of low-virulence anaerobic bacteria in degenerated IVDs, and P. acnes was the most frequent bacterium. In addition, the latent infection of bacteria in IVDs was associated with Modic changes. Therefore, low-virulence anaerobic bacteria may play a crucial role in the pathophysiology of MCs and lumbar disc herniation.
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Infecciones por Bacterias Grampositivas/microbiología , Degeneración del Disco Intervertebral/microbiología , Desplazamiento del Disco Intervertebral/microbiología , Disco Intervertebral/microbiología , Vértebras Lumbares/microbiología , Propionibacterium acnes/patogenicidad , Infecciones Estafilocócicas/microbiología , Staphylococcus/patogenicidad , Adulto , Anciano , Discectomía , Femenino , Infecciones por Bacterias Grampositivas/diagnóstico , Humanos , Disco Intervertebral/diagnóstico por imagen , Disco Intervertebral/cirugía , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/cirugía , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Propionibacterium acnes/aislamiento & purificación , Índice de Severidad de la Enfermedad , Infecciones Estafilocócicas/diagnóstico , Staphylococcus/aislamiento & purificación , Técnicas de Cultivo de Tejidos , VirulenciaRESUMEN
Accumulating evidence suggests that Propionibacterium acnes (P. acnes) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD). However, the underlying mechanisms by which P. acnes induces IVDD have been unclear. In this study, we quantified the severity of IVDD, as well as the expressions of inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and cyclooxygenase (COX-2)/prostaglandin (PGE2) in human intervertebral discs (IVDs) infected with P. acnes. Compared with P. acnes-negative IVDs, P. acnes-positive IVDs showed increased iNOS/NO and COX-2/PGE2 activity concomitant with more severe IVDD. In order to detect the potential correlation between iNOS/NO expression, COX-2/PGE2 expression, and IVDD, we developed a P. acnes-induced IVDD rat model and found that the upregulation of iNOS/NO and COX-2/PGE2 was essential to the occurrence of P. acnes-induced IVDD. This finding was supported by the fact that the inhibition of iNOS/NO and COX-2/PGE2 activity ameliorated IVDD significantly, as evidenced by restored aggrecan and collagen II expression both in vivo and in vitro. Mechanistically, we found that P. acnes induced iNOS/NO and COX-2/PGE2 expressions via a reactive oxygen species- (ROS-) dependent NF-κB cascade. Furthermore, NADPH oxidase participated in P. acnes-induced ROS, iNOS/NO, and COX-2/PGE2 expressions. Overall, these findings further validated the involvement of P. acnes in the pathology of IVDD and provided evidence that P. acnes-induced iNOS/NO and COX-2/PGE2 activation via the ROS-dependent NF-κB pathway is likely responsible for the pathology of IVDD.
Asunto(s)
Ciclooxigenasa 2/metabolismo , Degeneración del Disco Intervertebral/etiología , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Propionibacterium acnes/patogenicidad , Especies Reactivas de Oxígeno/metabolismo , Adulto , Animales , Femenino , Humanos , Degeneración del Disco Intervertebral/patología , Masculino , Persona de Mediana Edad , Ratas , Ratas Sprague-DawleyRESUMEN
Acne vulgaris, a chronic inflammatory skin disease, affects many adolescents. New therapeutic agents for acne allow for a higher therapeutic activity, but fewer side effects. Tanshinone IIA, a natural product, has been proved to exhibit antibacterial and anti-inflammatory abilities in many diseases. However, its antibacterial and anti-inflammatory activities against Propionibacterium acnes have not been described. In the present study, the broth microdilution method was used to evaluate the antibacterial activity of tanshinone IIA and it had an inhibitory effect on the growth of P. acnes. Enzyme-linked immunosorbent assay and quantitative real-time PCR were used to investigate the effect of tanshinone IIA on IL-1ß, IL-8, and TNF-α expression, and western blot was used to examine TLR2, NF-κB, and intercellular cell adhesion molecule-1 (ICAM-1) protein level induced by P. acnes in THP-1 cells. Results showed that the expression of inflammatory cytokines and TLR2, NF-κB, ICAM-1 protein levels were inhibited by Tanshinone IIA, suggesting that tanshinone IIA appeared to suppress P. acnes-induced inflammation by blockade of TLR2/NF-κB signaling pathway. In conclusion, the present study revealed the inhibitory effect of tanshinone IIA on P. acnes-induced inflammation, providing an evidence to support the mechanism of anti-acne properties of tanshinone IIA.
Asunto(s)
Abietanos/farmacología , Acné Vulgar/tratamiento farmacológico , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Monocitos/efectos de los fármacos , Propionibacterium acnes/efectos de los fármacos , Acné Vulgar/inmunología , Acné Vulgar/metabolismo , Acné Vulgar/microbiología , Citocinas/metabolismo , Interacciones Huésped-Patógeno , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/microbiología , Mediadores de Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Monocitos/inmunología , Monocitos/metabolismo , Monocitos/microbiología , FN-kappa B/metabolismo , Propionibacterium acnes/metabolismo , Propionibacterium acnes/patogenicidad , Transducción de Señal/efectos de los fármacos , Células THP-1 , Receptor Toll-Like 2/metabolismoRESUMEN
Acne is based on a complex, multifactorial pathophysiology beginning with a microcomedo. Comedogenesis involves follicular hyperproliferation and disturbed keratinization, hyperseborrhea and hyperplasia of sebaceous glands as well as disturbances in skin microbiome. Acne is treated with antibiotics, retinoids, keratolytics, hormonal and anti-inflammatory agents. Efficacy and side effects of given medications are well known. The uppermost layer of the stratum corneum is acidic. The low pH provides protection by slowing down the growth of some bacteria. Increase of skin surface pH leads to impaired barrier function, disturbances in skin microbiome and inflammation. Acne-predisposed skin is in a constant state of subclinical inflammation. Subclinical inflammation may be linked to changes in skin surface pH and disturbances of the stratum corneum, allowing microorganisms to stimulate the production of pro-inflammatory cytokines. Here, based on the current literature, the possible link between the skin surface pH, epidermal barrier function and acne is reviewed.
Asunto(s)
Acné Vulgar/metabolismo , Piel/metabolismo , Acné Vulgar/etiología , Acné Vulgar/terapia , Envejecimiento/metabolismo , Animales , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Propionibacterium acnes/crecimiento & desarrollo , Propionibacterium acnes/patogenicidad , Caracteres Sexuales , Piel/química , Pigmentación de la PielRESUMEN
In this study, we investigated the anti-microbial, anti-inflammatory, and anti-lipogenic effects of hemp (Cannabis sativa L.) seed hexane extracts, focusing on the Propionibacterium acnes-triggered inflammation and lipogenesis. Hemp seed hexane extracts (HSHE) showed anti-microbial activity against P. acnes. The expression of iNOS, COX-2, and the subsequent production of nitric oxide and prostaglandin increased after infection of P. acnes in HaCaT cells, however, upon treating with HSHE, their expressions were reduced. P. acnes-induced expressions of IL-1ß and IL-8 were also reduced. HSHE exerted anti-inflammatory effects by regulating NF-κB and MAPKs signaling and blunting the translocation of p-NF-κB to the nucleus in P. acnes-stimulated HaCaT cells. Moreover, P. acnes-induced phosphorylation of ERK and JNK, and their downstream targets c-Fos and c-Jun, was also inhibited by HSHE. In addition, the transactivation of AP-1 induced by P. acnes infection was also downregulated by HSHE. Notably, HSHE regulated inflammation and lipid biosynthesis via regulating AMPK and AKT/FoxO1 signaling in IGF-1-induced inflammation and lipogenesis of sebocytes. In addition, HSHE inhibited 5-lipoxygenase level and P. acnes-induced MMP-9 activity, and promoted collagen biosynthesis in vitro. Thus, HSHE could be utilized to treat acne vulgaris, through its anti-microbial, anti-inflammatory, anti-lipogenic, and collagen-promoting properties.