Secretion of biologically active human interleukin 22 (IL-22) by Lactococcus lactis

Loera‐Arias, María de Jesús; Villatoro-Hernandez, Julio; Parga-Castillo, Miguel A.; Salcido‐Montenegro, Alejandro; Barboza-Quintana, Oralia; Muñoz-Maldonado, Gerardo Enrique; Montes‐de‐Oca‐Luna, Roberto; Saucedo‐Cárdenas, Odila

doi:10.1007/s10529-014-1626-y

Cited by 11 publications

(12 citation statements)

References 17 publications

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“…The use of lactobacilli as vectors to deliver protein has been reported in models of colitis, in which IL-10 delivered by Lactobacillus casei was shown to ameliorate inflammation ( 36 ). Further, L. lactis producing active IL-22 is a promising system as a living vaccine adjuvant ( 37 ). Lactobacilli produce lactic acid and thereby reduce local pH when applied to wounds.…”

Section: Discussionmentioning

confidence: 99%

Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria

Vågesjö

Öhnstedt

Mortier

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

120

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SignificanceChronic wounds comprise a growing clinical problem that represents >3% of the health care budget in industrialized countries. Drug development is hampered by the proteolytic nature of the wounds, which greatly limits drug bioavailability. Here, we present a technology that circumvents this by on-site production and reduced chemokine degradation. Lactobacilli bacteria were transformed into CXCL12-producing vectors to bioengineer the wound microenvironment after topical application. Consequently, the immune cells driving the healing process were reinforced, which greatly accelerated wound closure in healthy mice, in mouse models of hyperglycemia and peripheral ischemia, and in a wound model using human skin disks. Initial safety studies demonstrated that neither bacteria nor the chemokine produced was detected in systemic circulation following application to open wounds.

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Section: Discussionmentioning

confidence: 99%

Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria

Vågesjö

Öhnstedt

Mortier

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

120

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“…Lactococcus lactis has previously been used to secrete IL-22 under a nisin-inducible promoter [ 20 ]. However, Lactococcus does not colonize the intestinal tract and the inducible promoter is not suitable for gastrointestinal delivery.…”

Section: Introductionmentioning

confidence: 99%

Lactobacillus delivery of bioactive interleukin-22

et al. 2017

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BackgroundInterleukin-22 (IL-22) plays a prominent role in epithelial regeneration and dampening of chronic inflammatory responses by protecting intestinal stem cells from immune-mediated tissue damage. IL-22 has a considerable therapeutic potential in graft-versus-host disease (GVHD), which is a frequent and challenging complication following allogeneic stem cell transplantation. The aim of our study was to engineer Lactobacillus for delivery of IL-22 directly to the intestinal mucosa as a new therapeutic strategy for GVHD.ResultsThe secretion and surface anchoring of mouse IL-22 by Lactobacillus paracasei BL23 was demonstrated by Western blot and flow cytometry. Both secreted and anchored mouse IL-22 produced by Lactobacillus was biologically active, as determined by its ability to induce IL-10 secretion in the Colo 205 human colon cancer cell line.ConclusionsWe have demonstrated the secretion and surface anchoring of bioactive IL-22 by Lactobacillus. Our results suggest that IL-22 expressing lactobacilli may potentially be a useful mucosal therapeutic agent for the treatment of GVHD, provided that chromosomal integration of the IL-22 expression cassettes can be achieved.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-017-0762-1) contains supplementary material, which is available to authorized users.

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“…lactis that can deliver therapeutic molecules for treating infectious or gastrointestinal diseases as well as allergies has been well documented (Bermudez-Humaran et al 2011, Pontes et al 2011, Wells 2011). Therefore, L. lactis has a great potential for use in clinical settings (Bermudez-Humaran et al 2005, Loera-Arias et al 2014, Villatoro-Hernandez et al 2008). …”

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confidence: 99%

Development ofLactococcus lactisencoding fluorescent proteins, GFP, mCherry and iRFP regulated by the nisin-controlled gene expression system

Martinez-Jaramillo

Garza-Morales

Loera‐Arias

et al. 2017

Biotechnic & Histochemistry

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Fluorescent proteins are useful reporter molecules for a variety of biological systems. We present an alternative strategy for cloning reporter genes that are regulated by the nisin-controlled gene expression (NICE) system. Lactoccocus lactis was genetically engineered to express green fluorescent protein (GFP), mCherry or near-infrared fluorescent protein (iRFP). The reporter gene sequences were optimized to be expressed by L. lactis using inducible promoter pNis within the pNZ8048 vector. Expression of constructions that carry mCherry or GFP was observed by fluorescence microscopy 2 h after induction with nisin. Expression of iRFP was evaluated at 700 nm using an infrared scanner; cultures induced for 6 h showed greater iRFP expression than non-induced cultures or those expressing GFP. We demonstrated that L. lactis can express efficiently GFP, mCherry and iRFP fluorescent proteins using an inducible expression system. These strains will be useful for live cell imaging studies in vitro or for imaging studies in vivo in the case of iRFP.

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Secretion of biologically active human interleukin 22 (IL-22) by Lactococcus lactis

Cited by 11 publications

References 17 publications

Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria

Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria

Lactobacillus delivery of bioactive interleukin-22

Development ofLactococcus lactisencoding fluorescent proteins, GFP, mCherry and iRFP regulated by the nisin-controlled gene expression system

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