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A Food-Grade, Secretory Expression of IL1RA Protein in a Lactococcus Lactis System for Potential Oral Therapy on IBD

Interleukin 1β (IL1β) is a potential target for IBD treatment. IL1 receptor antagonist (IL1RA) can blocks the biologic activity of IL1 by competitively inhibiting IL1 binding to the IL1R, so IL1RA is suggested to have possible therapeutic applications in treatment of IBD. By using a food-grade recombinant Lactococcus lactis system, a constitutive expression vector IL1RA:pNZ8149 was constructed and transferred into a L. lactis host NZ3900 in this study. The engineered strain was fermented and detected by colonies PCR and Western blot, the results indicate that the IL1RA secretory expression can be archived by IL1RA/NZ3900. Introduction Interleukin 1 (IL1) plays a significant role in the regulation of immune and inflammatory responses to infections. IL1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses. IL1β is a member of IL1 family, the pro-inflammatory effect of which has been proved recent years. Research results suggest that IL1β contributes to chronic intestinal inflammation, such as inflammatory bowel disease (IBD). IL1β is secreted from intestinal tissues and macrophages isolated from patients with IBD, and IL1β levels correlate with disease severity [1, 2]. Therefore, IL1β can be a potential target for IBD treatment [2, 9], the IL1β signaling pathway inhibition is an effective way for treatment of IBD. The naturally occurring endogenous IL1 receptor antagonist (IL1RA), formerly called the IL-1 inhibitor, is a member of the IL1 cytokine family which binds to IL1 receptors with an affinity similar to that of IL1α and IL1β, but does not induce a signaling response [10]. Thus, IL1RA can blocks the biologic activity of IL1 by competitively inhibiting IL1 binding to the IL1R (fig. 1), which is expressed in a wide variety of tissues and organs [11]. In terms of protein similarities, IL1RA is more closely related to IL1β than it is to IL1α. IL1RA is suggested to have possible therapeutic applications in treatment of many diseases, including IBD [1, 2, 6, 12-14]. However, as a protein, the disadvantages of IL1RA are the short half-time by injection, low targeting and oral therapy inactivation. 386 This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/). Copyright © 2017, the Authors. Published by Atlantis Press. 2nd International Conference on Biomedical and Biological Engineering 2017 (BBE 2017) Advances in Biological Sciences Research (ABSR), volume 4