Recombinant Lactococcus lactis expressing porcine insulin-like growth factor I ameliorates DSS-induced colitis in mice

Abstract

BackgroundInsulin-like growth factor I (IGF-I) is one important family of growth factors, which plays key role in intestinal growth, regeneration, and damage repair. However, the low natural abundance of IGF-I limits its research opportunities and practical application in the fields of medicine and animal husbandry. In this study, a tandem repeat strategy was used to express three copies of the same pIGF-I3 protein in L. lactis. The activity of recombinant pIGF-I3 (rpIGF-I3) was further examined by a mouse model of dextran sulfate sodium (DSS)–induced colitis. In addition, the potential of recombinant L. lactis expressing pIGF-I3 to reduce inflammatory disease was evaluated.ResultspIGF-I3 could be expressed in L. lactis by the detection of SDS–PAGE and Western blot. Experimental colitis was induced in BALB/c mice by administration of 5 % DSS in drinking water, and the clinical symptoms were observed in DSS-treated mice. Oral administration of recombinant L. lactis expressing pIGF-I3 improved the colonic architecture, and significantly reduced the increase of colonic damage score (P < 0.05). Furthermore, recombinant L. lactis expressing pIGF-I3 treatment significantly reduced serum DAO activity and colonic MPO level, and elevated colonic occludin level compared to the DSS group (P < 0.05).ConclusionsThe pIGF-I3 expressed in L. lactis has good biological activity, and oral administration of recombinant L. lactis expressing pIGF-I3 attenuated the symptoms and development of DSS-induced colitis in mice. These suggested that L. lactis could be a potential host bacterium for production and delivery of IGF-I against intestinal diseases.

A review on Lactococcus lactis: from food to factory

“…To date, L. lactis has been used to co-produce or secrete a wide range of other adjuvants and growth factors. Successful examples include murine IL-12 [81], transforming growth factor beta 1 (TGF-β1) [82], insulin-like growth factor I [83], receptor activator of nuclear factor kappa-B ligand (RANKL) [84] and others as detailed in Table 2.…”

“…Through technological advancements in expression and secretion systems, consecutive attempts were proven more successful when oral administration of recombinant lactococcal strains secreting Cu–Zn superoxide dismutase (SOD) of B. abortus was found to render protective immunity against brucellosis when tested in mice [116]. Very recently, oral administration of recombinant insulin-like growth factor I (IGF-I) expressed in L. lactis also reported good biological activity, where symptoms and development of dextran sodium sulphate (DSS)-induced colitis in mice were attenuated [83]. Use of L. lactis has also made hallmarks in the aquaculture industry where lactococcal-based vaccines against Aeromonas hydrophila using D1 and D4 aerolysin genes were developed with increased survival in tilapia fish when administered intraperitoneally and orally [117].…”

Activation of GABAA Receptors in Colon Epithelium Exacerbates Acute Colitis

“…Total scores represented that of the sum of individual scores. Colonic damage score was the sum of individual scores ( 24 ).…”

Neutralizing-antibody-mediated protection of chickens against infectious bursal disease via one-time vaccination with inactivated recombinant Lactococcus lactis expressing a fusion protein constructed from the RCK protein of Salmonella enterica and VP2 of infectious bursal disease virus

“…This wealth of knowledge and experience has led to the use of Lactococcus in several fields of biotechnology, e.g. the expression of bacterial and viral antigens for safe vaccination via mucosal immunization, the availability of an easy-to-operate and strictly controlled gene expression system (NICE ® ) has been crucial for the development of many of these applications [18, 32–36].…”

“…Together, Lactococcus lactis NZ3900 and the pNZ8149 vector constitute a tightly-controlled Nisin-regulated gene expression system (NICE ® ) developed by NIZO Food Research, NL [19, 37, 38]. This system is easy to operate and is advantageous for over-expressing homologous and heterologous genes for functional studies and for obtaining large quantities of specific gene products [18, 32–36].…”