RESUMO
One of the primary theories regarding the development of schizophrenia revolves around genetics, indicating the involvement of hereditary factors in various processes, including inflammation. Research has demonstrated that inflammatory reactions occurring in microglia can impact the progression of the disease. It has also been established that genetically determined changes in IL-1 can contribute to schizophrenia, thereby confirming the role of the IL-1 gene cluster in disease susceptibility. The aim of this study is a computer-based assessment of the structural interactions of IL-1 proteins with their receptors in schizophrenia. The study utilized the DisGeNET database, enabling the assessment of the reliability of identified IL-1 polymorphisms. Polymorphisms were also sought using NCBI PubMed. The NCBI Protein service was employed to search for and analyze the position of the identified polymorphisms on the chromosome. Structures for modeling were extracted from the Protein Data Bank database. Protein modeling was conducted using the SWISS-MODEL server, and protein interaction modeling was performed using PRISM. Notably, this study represents the first prediction of the interactions of IL-1α, IL-1ß, and IL- 1RA proteins, taking into account the presence of single-nucleotide polymorphisms associated with schizophrenia in the sequence of the corresponding genes. The results indicate that the presence of SNP rs315952 in the IL-1RA protein gene, associated with schizophrenia, may lead to a weakening of the IL-1RA binding to receptors, potentially triggering the initiation of the IL-1 signaling pathway by disrupting or weakening the IL-1RA binding to receptors and facilitating the binding of IL-1 to them. Such alterations could potentially lead to a change in the immune response. The data obtained contribute theoretically to the development of ideas about the molecular mechanisms through which hereditary factors in schizophrenia influence the interactions of proteins of the IL-1 family, which play an important role in the processes of the immune system.
RESUMO
The effect of recombinant TNF-α on programmed death of donor lymphocytes was studied in vitro. The proapoptotic effect of this cytokine is realized through transcription factors and cell cycle inhibitors. Incubation of lymphocytes with recombinant TNF-α revealed increased levels of NF-kB and p21 and reducted content of nonphosphorylated p53.
Assuntos
Apoptose/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Linfócitos/efeitos dos fármacos , NF-kappa B/metabolismo , Proteínas Recombinantes/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Adulto , Apoptose/fisiologia , Feminino , Citometria de Fluxo , Humanos , Técnicas In Vitro , Linfócitos/fisiologia , Masculino , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
We studied in vitro effects of recombinant interleukin-5, interleukin-3, and eotaxin on programmed death of eosinophils from healthy donors and patients with non-Hodgkin's lymphomas associated with severe blood eosinophilia. Interleukin-5 and eotaxin produced the most potent antiapoptotic effect on eosinophils from healthy donors. In patients with non-Hodgkin's lymphomas, spontaneous apoptosis in eosinophilic leukocytes was low and remained unchanged during incubation with recombinant proteins.
