RESUMO
Artesunate (ART), a derivative of artemisinin, is a medication to treat malaria. Beyond that, the anti-inflammatory and immunoregulatory activities of ART have been identified in autoimmune diseases. However, whether ART functions in psoriasis-like dermatitis induced by imiquimod (IMQ, a TLR7/8 agonist) is currently unkown. There, we found that the cumulative score, epidermal thickening and expression of Ki-67 of ART-treated BALB/c mice were significantly lower than those in the IMQ psoriatic model group. In addition, ART treatment ameliorated mice from systemic inflammation. Mechanistically, ART reduced γδ T cells in draining lymph nodes, which might be benefit the improvement of dermatitis. These findings suggested that ART could be a promising drug of psoriasis in clinic.
Assuntos
Anti-Inflamatórios/uso terapêutico , Artesunato/uso terapêutico , Dermatite/tratamento farmacológico , Psoríase/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Artesunato/farmacologia , Dermatite/imunologia , Dermatite/patologia , Imiquimode , Linfócitos Intraepiteliais/efeitos dos fármacos , Linfócitos Intraepiteliais/imunologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Masculino , Camundongos Endogâmicos BALB C , Psoríase/imunologia , Psoríase/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Células Th17/efeitos dos fármacos , Células Th17/imunologiaRESUMO
BACKGROUND: The A/H3N2 influenza viruses circulated in humans have been shown to undergo antigenic drift, a process in which amino acid mutations result from nucleotide substitutions. There are few reports regarding the charged amino acid mutations. The purpose of this paper is to explore the relations between charged amino acids, N-glycosylation and epitopes in hemagglutinin (HA) and neuraminidase (NA). METHODS: A total of 700 HA genes (691 NA genes) of A/H3N2 viruses were chronologically analyzed for the mutational variants in amino acid features, N-glycosylation sites and epitopes since its emergence in 1968. RESULTS: It was found that both the number of HA N-glycosylation sites and the electric charge of HA increased gradually up to 2016. The charges of HA and HA1 increased respectively 1.54-fold (+7.0 /+17.8) and 1.08-fold (+8.0/+16.6) and the number of NGS in nearly doubled (7/12). As great diversities occurred in 1990s, involving Epitope A, B and D mutations, the charged amino acids in Epitopes A, B, C and D in HA1 mutated at a high frequency in global circulating strains last decade. The charged amino acid mutations in Epitopes A (T135K) has shown high mutability in strains near years, resulting in a decrease of NGT135-135. Both K158N and K160T not only involved mutations charged in epitope B, but also caused a gain of NYT158-160. Epitope B and its adjacent N-glycosylation site NYT158-160 mutated more frequently, which might be under greater immune pressure than the rest. CONCLUSIONS: The charged amino acid mutations in A/H3N2 Influenza play a significant role in virus evolution, which might cause an important public health issue. Variability related to both the epitopes (A and B) and N-glycosylation is beneficial for understanding the evolutionary mechanisms, disease pathogenesis and vaccine research.
Assuntos
Epitopos/metabolismo , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A Subtipo H3N2/metabolismo , Neuraminidase/metabolismo , Aminoácidos/metabolismo , Antígenos Virais/química , Antígenos Virais/imunologia , Antígenos Virais/metabolismo , Epitopos/química , Epitopos/imunologia , Evolução Molecular , Variação Genética , Glicosilação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/classificação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Influenza Humana/patologia , Influenza Humana/virologia , Mutação , Neuraminidase/química , Neuraminidase/classificação , Filogenia , Estrutura Terciária de Proteína , RNA Viral/química , RNA Viral/isolamento & purificação , RNA Viral/metabolismo , Análise de Sequência de RNARESUMO
According to pathogenic surveillance data during the first half of 2012, the H3N2 influenza virus was prevalent in Guangdong, China, but no pandemic H1N1 (pH1N1) virus was detected. This study aimed to measure the seroprevalence of pH1N1 and H3N2 infection following the influenza epidemic in 2012. We collected serum samples by stratified random sampling in a cross-sectional survey from August, 2012 to October, 2012. Antibody titers against H3N2, pH1N1, and influenza B antigens were measured by the hemagglutination inhibition (HI) assay, and age-specific seroprevalence and non-immunity were calculated. A total of 566 serum samples were collected from subjects who had not received an influenza vaccination. The seroprevalence of H3N2, pH1N1, and influenza B were 61.7%, 31.3%, and 40.4%, respectively, while non-immunity was calculated to be 9.2%, 40.6%, and 27.0%, respectively. The highest recorded seroprevalence was 86.0% for H3N2 in the 6-15 year age group, while the lowest was 14.6% for pH1N1 in the 60+ age group. Non-immunity fractions were 44.4% and 53.5% in the 0-6 and 60+ age groups, respectively. In conclusion, the seroprevalence of pH1N1 remained below 50% in all age groups following the 2012 influenza season. These data suggest that vaccination against pH1N1 antigens should be conducted, especially in the older age groups, before the next influenza season.
