Utilização biotecnológica de Lactococcus lactis como veículo de liberação da 15-Lipoxigenase-1 no tratamento de doenças inflamatórias intestinais

• Ano de defesa: 2014
• Autor(a) principal: Katia de Morais Costa Leite
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Lactococcus lactis; Biotecnologia; Colite; Lipoxigenase; Inflamação; Biofarmácia
• Link de acesso: http://hdl.handle.net/1843/BUBD-9VEFRD

Functional foods that are able to promote human health have been the focus of several studies. Fermented milks, cheeses and yogurts produced by some probiotic lactic acid bacteria (LAB) strains are an example as they can exert beneficial effects on the host. The model LAB, Lactococcus lactis, has a great economic importance as it is safe for human consumption and widely used for industrial dairy fermentations. Therefore, L. lactis has been engineered to express and secrete a variety of therapeutic molecules. Recent studies showed the therapeutic potential of recombinant L. lactis strains in the treatment of some diseases, such as inflammatory bowel diseases (IBDs). IBDs are characterized by severe inflammation of the gastrointestinal tract. Its etiology is not well understood and the treatments available may have serious side effects. In this context, the use of recombinant L. lactis strains expressing molecules with potential anti-inflammatory properties, such as 15-Lipoxygenase-1 (15-LOX-1), represents an interesting alternative. 15-LOX-1 is an enzyme involved in fatty acid metabolism, which is known for its strong antiinflammatory activity. Thus, this project aimed to construct L. lactis strains able to express 15-LOX-1 and verify its anti-inflammatory capacity in a chemically induced mouse model of intestinal inflammation (DSS). The strain expressing the cytoplasmic form of the enzyme was able to decrease inflammation in treated animals by reducing the levels of proinflammatory cytokines (IFN-, IL-17, IL-4) and increasing the regulatory cytokine IL-10. No differences were observed in the levels of secretory IgA among treated and untreated groups. This study showed recombinant L. lactis strains expressing 15-Lipoxygenase-1 (15-LOX-1) was able to reduce damage in colon segments from treated animals. Taken together, this strategy appeared to be very promising for the treatment of IBDs in the near future.