RESUMO
The complement component 5a/complement component 5 receptor 1 (C5a/C5aR1) pathway plays a crucial role in the onset and development of inflammation, but relevant studies in fish are lacking. In this study, we successfully characterized the relationship between half-smooth tongue sole (Cynoglossus semilaevis) C5aR1 (CsC5aR1) and bacterial inflammation. First, we showed that the overexpression of CsC5aR1 significantly increased bacterial pathological damage in the liver and intestine, whereas inhibition attenuated the damage. The in vitro experiments suggested that CsC5aR1 was able to positively regulate the phagocytic activity and respiratory burst of tongue sole macrophages. In terms of both transcriptional and translational levels, overexpression/inhibition of CsC5aR1 was followed by a highly consistent up-regulation/decrease of its downstream canonical inflammatory factor interleukin-6 (CsIL-6). Furthermore, we stimulated macrophages by lipopolysaccharide (LPS) and lipoteichoic acid (LTA) and found a broad-spectrum response to bacterial infections by the C5a/C5aR1 complement pathway together with the downstream inflammatory factor CsIL-6. Subsequently, we directly elucidated that CsIL-6 is an indicator of C5a/C5aR1-mediated inflammation at different infection concentrations, different infectious bacteria (Vibrio anguillarum and Mycobacterium marinum), and different detection levels. These results might provide a new inflammation bio-marker for early warning of bacteria-induced hyperinflammation leading to fish mortality and a promising target for the treatment of bacterial inflammation in teleost.
Assuntos
Doenças dos Peixes , Proteínas de Peixes , Linguados , Interleucina-6 , Receptor da Anafilatoxina C5a , Animais , Linguados/imunologia , Linguados/genética , Receptor da Anafilatoxina C5a/genética , Receptor da Anafilatoxina C5a/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-6/metabolismo , Vibrioses/veterinária , Vibrioses/imunologia , Vibrio/fisiologia , Inflamação/imunologia , Inflamação/veterinária , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genéticaRESUMO
The ubiquitin-proteasome system is the primary cellular pathway for protein degradation, mediating 80% of intracellular protein degradation. Because of the widespread presence of ubiquitin-modified protein substrates, ubiquitination can regulate a variety of cellular activities including cell proliferation, apoptosis, autophagy, endocytosis, DNA damage repair, and immune responses. With the continuous generation of genomics data in recent years it has become particularly important to analyze these data effectively and reasonably. Cacybp forms a complex with the E3 ubiquitinated ligase Siah1 to participate in ubiquitination. We analyzed Cacybp-associated genes using the Gene Expression Omnibus (GEO) and CGGA (Chinese Glioma Genome Atlas) databases and identified 121 differentially expressed genes (DEGs), of which 46 were downregulated and 75 were upregulated. The biological processes, molecular functions, and protein-protein interaction (PPI) network of differential genes were analyzed by Cytoscape software and STRING software. We found no difference in Cacybp expression among different grades of gliomas and there was no significant association between the expression level of Cacybp and the prognosis of patients with glioma in LGG and GBM. © 2019 IUBMB Life, 1-8, 2019.
Assuntos
Biomarcadores Tumorais/genética , Proteínas de Ligação ao Cálcio/metabolismo , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Glioma/metabolismo , Proteínas de Ligação ao Cálcio/genética , Bases de Dados Factuais , Feminino , Perfilação da Expressão Gênica , Glioma/genética , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Mapas de Interação de Proteínas , Taxa de SobrevidaRESUMO
RATIONALE: Childhood chronic myeloid leukemia (CCML) is a malignant disease of granulocyte abnormal hyperplasia that is caused by clonal proliferation of pluripotent stem cells. The condition is relatively rare, accounting for 2.0% to 3.0% of cases of childhood leukemia. In addition, the incidence of extramedullary blast crisis in CCML presenting as central nervous system (CNS) blast crisis remaining chronic phase of the disease in bone marrow is extremely unusual. PATIENT CONCERNS: We report a case of childhood chronic myelogenous leukemia that abandoned treatment, resulting in chronic myelogenous leukemia transforming into extramedullary blast crisis resulting in CNS leukemia, accompanied by the chronic phase of the disease in bone marrow. DIAGNOSES: Chronic myeloid leukemia extramedullary blast crisis presenting as CNS leukemia without blast crisis in bone marrow. INTERVENTIONS: Following high-dose systemic and intrathecal chemotherapy, the patient continued to do well. LESSONS: High-dose systemic and intrathecal chemotherapy is safe and helpful for CCML extramedullary blast crisis. A long-term follow-up is crucial.