Assuntos
Glucocorticoides/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunoglobulinas Intravenosas/administração & dosagem , Dermatopatias/tratamento farmacológico , Doença Aguda/terapia , Adulto , Biópsia , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Evolução Fatal , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Pele/patologia , Dermatopatias/diagnóstico , Dermatopatias/etiologia , Dermatopatias/patologia , Transplante Homólogo/efeitos adversos , Resultado do TratamentoRESUMO
Immune activation and inflammation are closely associated with the development of depression. Pioglitazone (PIO), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, has exhibited antidepressant-like effects in a couple of studies. However, the underlying mechanisms are far from being fully elucidated. The study aimed to investigate the effects of PIO on depression-like behaviors induced by lipopolysaccharide (LPS) and to explore the possible underlying mechanisms. The results showed that PIO pretreatment attenuated the depression-like behaviors in mice challenged with intracerebroventricular (i.c.v.) LPS administration. Moreover, Western blot analysis revealed the effects of PIO on inhibiting activation of the nuclear factor kappa B/interleukin 6/signal transducer and activator of transcription 3 (NF-κB/IL-6/STAT3) pathway, improving down-regulation of the cAMP response-element-binding protein/brain derived neurotrophic factor (CREB/BDNF) pathway, as well as regulating disturbed expression of proteins involved in central serotonergic neurotransmission following LPS administration. The beneficial effects of PIO, at both the behavioral and molecular level, were significantly inhibited by the PPAR-γ specific antagonist GW9662. In summary, our data reveals for the first time that the modulation of the NF-κB/IL-6/STAT3 and CREB/BDNF pathways, as well as the potential impact on central serotonergic neurotransmission, may be involved in the PPAR-γ-dependent effects of PIO on depression-like behaviors induced by LPS. Additionally, our findings may provide a novel therapeutic target for the treatment of depression-like behaviors in patients with inflammatory status.
Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Neurônios Serotoninérgicos/fisiologia , Tiazolidinedionas/uso terapêutico , Anilidas/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células Cultivadas , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Humanos , Interleucina-6/metabolismo , Lipopolissacarídeos/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , PPAR gama/metabolismo , Pioglitazona , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Transmissão SinápticaRESUMO
Forty bacterial isolates from the effluents of a gelatin factory (Jabalpur, India) were screened for protease activity and the two most potent producers were identified as Bacillus laterosporus and a Flavobacterium sp. The enzymes of both isolates were optimal at pH 8 and 60°C, with maximum activity after 90 min. The enzyme activity of B. laterosporus was suppressed by Fe(2+), Mg(2+), Mn(2+) and Zn(2+) ions but was enhanced by Ba(2+) and Ca(2+). That of Flavobacterium sp. was suppressed by Mg(2+) and Mn(2+) ions but enhanced by Ba(2+), Ca(2+) and Fe(2+). The enzyme activity of the former was strongly inhibited by KCN, whereas that of the latter was only slightly inhibited by 8-hydroxyquinoline.