RESUMO
Bitis arietans is a snake of medical importance found throughout sub-Saharan Africa and in savannas and pastures of Morocco and western Arabia. The effects of its venom are characterized by local and systemic alterations, such as inflammation and cardiovascular and hemostatic disturbances, which can lead to victims' death or permanent disability. To better characterize the inflammatory process induced by this snake's venom, the participation of eicosanoids and PAF (platelet- activating factor) in this response were demonstrated in a previous study. In addition, edema and early increased vascular permeability followed by an accumulation of polymorphonuclear (PMN) cells in the peritoneal cavity were accompanied by the production of the eicosanoids LTB4, LTC4, TXB2, and PGE2, and local and systemic production of IL-6 and MCP-1. In this context, the present study focused on the identification of inflammatory mediators produced by human macrophages derived from THP-1 cells in response to Bitis arietans venom (BaV), and Kn-Ba, a serine protease purified from this venom. Here, we show that Kn-Ba, and even the less intensive BaV, induced the production of the cytokine TNF and the chemokines RANTES and IL-8. Only Kn-Ba was able to induce the production of IL-6, MCP-1, and IP-10, whereas PGE2 was produced only in response to BaV. Finally, the release of IL-1ß in culture supernatants suggests the activation of the inflammasomes by the venom of Bitis arietans and by Kn-Ba, which will be investigated in more detail in future studies.
Assuntos
Citocinas/metabolismo , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Serina Proteases/farmacologia , Venenos de Víboras/química , Viperidae/fisiologia , Animais , Citocinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Serina Proteases/química , Serina Proteases/metabolismo , Células THP-1RESUMO
OBJECTIVES: To evaluate the mRNA expression levels of cytokines interferon-γ, tumour necrosis factor-α, interleukin IL-1ß, IL-10, and the chemokine CCL2/MCP-1, CCL4, and CXCR4 in the periapical interstitial fluid from root canal infections before and after bacterial load reduction in patients undergoing haematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS: The case group was composed of 10 patients undergoing HSCT, and our control group included 10 healthy patients. Clinical samples were taken from teeth with pulp necrosis. Three paper points were placed in the RCS and maintained for 2 min for microbial evaluation before cleaning and shaping procedures. After cleaning and drying the canal, three paper points were introduced into the root canal, passing passively through the root apex (2 mm) into the periapical tissues for 1 min. Samples were collected immediately after root canal cleaning and 7 days later (restrained root canal bacterial load) to characterize gene expression using real-time PCR. RESULTS: The results showed significantly reduction in the microbial load on day 7. An increased expression level of TNF-α and IFN-γ on day 7 in control and case groups was observed (p < 0.05). The mRNA levels of IL-1ß and IL-10 in the pre-HSCT group increased in the samples from day 7 (p < 0.05). The chemokine CCL-2/MCP-1 was not detected in pre-HSCT group. Chemokine receptor CXCR4 levels increased in samples obtained from the day 7 in the control group (p < 0.05). CONCLUSIONS: Individuals undergoing HSTC presented similar cytokine and chemokine mRNA expression compared with healthy individuals. However, it was observed the total absence of mRNA MCP-1/CCL2 expression in those individuals undergoing HSCT. CLINICAL RELEVANCE: Patients undergoing HSCT are at higher risk of infection. No study has analysed the periapical immune responses to root canal infections in HSCT individuals.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Periodontite Periapical , Citocinas , Necrose da Polpa Dentária , Humanos , Periodontite Periapical/terapia , Tecido Periapical , Tratamento do Canal RadicularRESUMO
Bitis arietans is a snake of medical importance found throughout sub-Saharan Africa and in savannas and pastures of Morocco and western Arabia. The effects of its venom are characterized by local and systemic alterations, such as inflammation and cardiovascular and hemostatic disturbances, which can lead to victims’ death or permanent disability. To better characterize the inflammatory process induced by this snake’s venom, the participation of eicosanoids and PAF (platelet- activating factor) in this response were demonstrated in a previous study. In addition, edema and early increased vascular permeability followed by an accumulation of polymorphonuclear (PMN) cells in the peritoneal cavity were accompanied by the production of the eicosanoids LTB4, LTC4, TXB2, and PGE2, and local and systemic production of IL-6 and MCP-1. In this context, the present study focused on the identification of inflammatory mediators produced by human macrophages derived from THP-1 cells in response to Bitis arietans venom (BaV), and Kn-Ba, a serine protease purified from this venom. Here, we show that Kn-Ba, and even the less intensive BaV, induced the production of the cytokine TNF and the chemokines RANTES and IL-8. Only Kn-Ba was able to induce the production of IL-6, MCP-1, and IP-10, whereas PGE2 was produced only in response to BaV. Finally, the release of IL-1β in culture supernatants suggests the activation of the inflammasomes by the venom of Bitis arietans and by Kn-Ba, which will be investigated in more detail in future studies.
RESUMO
BACKGROUND: Arboviruses co-circulating within a population that are transmitted by the same vector have the potential to cause coinfections. Coinfections with dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) have been occurring in Brazil, but it is not well-understood how human responses vary during mono- or coinfections and whether they play different roles in pathogenesis. METHODS: We investigated the clinical, virological, and immunological status during patients' acute infections, focusing on the CCL/CXC chemokines, proinflammatory, as well as anti-inflammatory cytokines levels quantified by ELISAs. Viral load was determined by qRT-PCR in serum samples from 116 acute DENV, ZIKV, CHIKV, DENV/ZIKV, and CHIKV/ZIKV-infected adult patients from Brazil. RESULTS: Most of the acute patients displayed fever, headache, prostration, and myalgia, regardless of the type of arbovirus infection. Zika viral load was higher in CHIKV/ZIKV coinfected patients compared with ZIKV or DENV/ZIKV infections. All infected individuals presented increased concentrations of C-X-C motif chemokine ligand 10/interferon protein-10 (CXCL10/IP-10), C-C motif chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1), and tumor necrosis factor alpha (TNF-α) compared to healthy donors. Interestingly, the ZIKV group separated from CHIKV/ZIKV due to higher levels of interleukin-10 (IL-10) and lower levels of TNF-α. While DENV/ZIKV differentiated from CHIKV due to their higher levels of CCL2/MCP-1, in CHIKV- and CHIKV/ZIKV-infected patients, levels of CXC10/IP-10, CCL2/MCP-1, and migration inhibitory factor (MIF) were associated with CHIKV viral load. By contrast, in DENV/ZIKV- and CHIKV/ZIKV-infected patients, levels of CXCL10/IP-10, CCL2/MCP-1, and TNF-α showed a significant inverse correlation with ZIKV viral load. CONCLUSIONS: From all the circulating mediators measured, we detected differences of IL-10, TNF-α, and CCL2/MCP-1 between arbovirus groups. We hypothesize that CXC10/IP-10, CCL2/MCP-1, and MIF in the CHIKV-infected group could regulate the CHIKV viral load, while CXC10/IP-10, CCL2/MCP-1, and TNF-α in DENV/ZIKV, and CHIKV/ZIKV groups, could regulate ZIKV viral load.
Assuntos
Febre de Chikungunya , Citocinas/sangue , Dengue , Infecção por Zika virus , Adulto , Brasil , Quimiocinas CC/sangue , Quimiocinas CXC/sangue , Febre de Chikungunya/imunologia , Febre de Chikungunya/virologia , Vírus Chikungunya/fisiologia , Coinfecção , Dengue/imunologia , Vírus da Dengue/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carga Viral , Adulto Jovem , Zika virus/fisiologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologiaRESUMO
A silicose representa um importante problema de saúde pública em todo o mundo, sobretudo nos países em desenvolvimento, sendo a principal causa de invalidez entre as doenças respiratórias ocupacionais. É uma pneumoconiose fibrótica, irreversível e potencialmente fatal, causada pela inalação de poeira contendo sílica cristalina. O diagnóstico é estabelecido através da história clínica e ocupacional de exposição à sílica, na presença de alterações radiológicas. Estudos experimentais e clínicos sugerem que a inalação da poeira da sílica está associada a um processo inflamatório pulmonar e sistêmico, mesmo em indivíduos que não desenvolveram silicose. Até o momento não existem exames laboratoriais específicos para o diagnóstico da doença, de modo que o conhecimento de marcadores biológicos associados à imunopatologia da silicose pode ser importante na detecção precoce da instalação e desenvolvimento da doença. O presente artigo traz uma revisão de estudos que investigaram os possíveis biomarcadores inflamatórios da doença no sangue e no lavado bronco-alveolar de humanos e de modelos experimentais.
Silicosis is an important public health problem worldwide, especially in developing countries and is the leading cause of disability among occupational respiratory diseases. It is a fibrotic disease irreversible and potentially fatal caused by inhaling dust containing crystalline silica, the most frequent type of pneumoconiosis. Diagnosis is established by clinical and occupational history of exposure to silica, in the presence of radiological changes. Experimental and clinical studies suggest that inhalation of silica dust is associated with pulmonary and systemic inflammation even in patients who did not develop silicosis. There are no specific tests for the routine laboratory diagnosis of the disease and the study of biological markers associated with the immunopathology of silicosis is important to understanding the establishment and development of silicosis. This article presents a review of studies investigating the possible inflammatory biomarkers of disease in blood and bronchoalveolar lavage from humans and experimental models.