Abstract

Intestinal fibrosis associated with Crohn’s disease (CD), which a common and serious complication of inflammatory bowel diseases. In this context, heat shock proteins (HSPs) might serve as an alternative treatment because these antigens play important roles in the regulation of effector T cells. We thus evaluated the anti-inflammatory and antifibrotic capacities of an invasive and Hsp65-producing strain—Lactococcus lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65)—in chronic intestinal inflammation to assess its potential as an alternative therapeutic strategy against fibrotic CD. Experimental colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in BALB/c mice, and the mice were treated orally with L. lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) via intragastric gavage. The oral administration of this strain significantly attenuated the severity of inflammation and intestinal fibrosis in mice (p < 0.05). These results are mainly justified by reductions in the levels of the pro-fibrotic cytokines IL-13 and TGF-β and increases in the concentration of the regulatory cytokine IL-10. The L. lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) strain contributed to reductions in the severity of inflammatory damage in chronic experimental CD, and these findings confirm the effectiveness of this new antifibrotic strategy based on the delivery of therapeutic proteins to inside cells of the host intestinal mucosa.

Highlights

  • Intestinal fibrosis associated with Crohn’s disease (CD), which a common and serious complication of inflammatory bowel diseases

  • CD, a multifactorial Inflammatory bowel diseases (IBDs) for which there is no cure, is characterized by chronic inflammation of the digestive system ­wall[10,23], and intestinal fibrosis is a recurrent complication of CD that can lead to serious damage, such as intestinal ­obstruction[8]

  • We adopted a model of chronic colitis chemically induced by trinitrobenzene sulfonic acid (TNBS) because the onset of inflammation is immediate, the procedure is relatively simple, and the induction produces a chronic inflammatory lesion associated with intestinal tissue ­fibrosis[21,24]

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Summary

Introduction

Intestinal fibrosis associated with Crohn’s disease (CD), which a common and serious complication of inflammatory bowel diseases In this context, heat shock proteins (HSPs) might serve as an alternative treatment because these antigens play important roles in the regulation of effector T cells. The L. lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) strain contributed to reductions in the severity of inflammatory damage in chronic experimental CD, and these findings confirm the effectiveness of this new antifibrotic strategy based on the delivery of therapeutic proteins to inside cells of the host intestinal mucosa. Therapies that modulate CD inflammation are currently available, there are no effective treatments to prevent or reverse fibrosis that affects carriers of the disease In this sense, heat shock proteins (HSPs), which are important antigens in regulating effector T cells during ­inflammation[11,12], can be promising candidates for the development of new antifibrogenic therapies

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