Secretion of biologically active pancreatitis-associated protein I (PAP) by genetically modified dairy Lactococcus lactis NZ9000 in the prevention of intestinal mucositis.

Autor:	Carvalho RD; Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil., Breyner N; Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-En-Josas, France., Menezes-Garcia Z; Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil., Rodrigues NM; Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil., Lemos L; Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil., Maioli TU; Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil., da Gloria Souza D; Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil.; Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-En-Josas, France., Carmona D; Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil., de Faria AM; Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil., Langella P; Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-En-Josas, France., Chatel JM; Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-En-Josas, France., Bermúdez-Humarán LG; Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-En-Josas, France., Figueiredo HC; Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil., Azevedo V; Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil., de Azevedo MS; Federal University of Minas Gerais (UFMG-ICB), Av. Antônio Carlos, 6627, CP 486, Belo Horizonte, MG, 31270-901, Brazil. marcela.spachecoazevedo@gmail.com.
Jazyk:	angličtina
Zdroj:	Microbial cell factories [Microb Cell Fact] 2017 Feb 13; Vol. 16 (1), pp. 27. Date of Electronic Publication: 2017 Feb 13.
DOI:	10.1186/s12934-017-0624-x
Abstrakt:	Background: Mucositis is one of the most relevant gastrointestinal inflammatory conditions in humans, generated by the use of chemotherapy drugs, such as 5-fluoracil (5-FU). 5-FU-induced mucositis affects 80% of patients undergoing oncological treatment causing mucosal gut dysfunctions and great discomfort. As current therapy drugs presents limitations in alleviating mucositis symptoms, alternative strategies are being pursued. Recent studies have shown that the antimicrobial pancreatitis-associated protein (PAP) has a protective role in intestinal inflammatory processes. Indeed, it was demonstrated that a recombinant strain of Lactococcus lactis expressing human PAP (LL-PAP) could prevent and improve murine DNBS-induced colitis, an inflammatory bowel disease (IBD) that causes severe inflammation of the colon. Hence, in this study we sought to evaluate the protective effects of LL-PAP on 5-FU-induced experimental mucositis in BALB/c mice as a novel approach to treat the disease. Results: Our results show that non-recombinant L. lactis NZ9000 have antagonistic activity, in vitro, against the enteroinvasive gastrointestinal pathogen L. monocytogenes and confirmed PAP inhibitory effect against Opportunistic E. faecalis. Moreover, L. lactis was able to prevent histological damage, reduce neutrophil and eosinophil infiltration and secretory Immunoglobulin-A in mice injected with 5-FU. Recombinant lactococci carrying antimicrobial PAP did not improve those markers of inflammation, although its expression was associated with villous architecture preservation and increased secretory granules density inside Paneth cells in response to 5-FU inflammation. Conclusions: We have demonstrated for the first time that L. lactis NZ9000 by itself, is able to prevent 5-FU-induced intestinal inflammation in BALB/c mice. Moreover, PAP delivered by recombinant L. lactis strain showed additional protective effects in mice epithelium, revealing to be a promising strategy to treat intestinal mucositis.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Plný text ve formátu PDF