scholarly journals Cells and Mediators of Inflammation as Effectors of Epithelial Repair in the Inflamed Intestine

Author(s):  
Bianca Crifo ◽  
Wallace K. MacNaughton

Mucosal and histological healing have become the gold standards for assessing the efficacy of therapy in patients living with inflammatory bowel diseases (IBD). Despite these being the accepted goals in therapy, the mechanisms that underlie the healing of the mucosa after an inflammatory insult are not well understood, and many patients fail to meet this therapeutic endpoint. Here we review the emerging evidence that mediators (e.g. prostaglandins, cytokines, proteases, reactive oxygen and nitrogen species) and innate immune cells (e.g. neutrophils and monocytes/macrophages), that are involved in the initiation of the inflammatory response, are also key players in the mechanisms underlying mucosal healing to resolve chronic inflammation in the colon. The dual function mediators comprise an inflammation/repair program that returns damaged tissue to homeostasis. Understanding details of the dual mechanisms of these mediators and cells may provide the basis for the development of drugs that can help to stimulate epithelial repair in patients affected by IBD.

2020 ◽  
Vol 26 (8) ◽  
pp. 1131-1143 ◽  
Author(s):  
Gwo-tzer Ho ◽  
Jennifer A Cartwright ◽  
Emily J Thompson ◽  
Calum C Bain ◽  
Adriano G Rossi

Abstract Despite significant recent therapeutic advances, complete mucosal healing remains a difficult treatment target for many patients with inflammatory bowel diseases (IBD) to achieve. Our review focuses on the translational concept of promoting resolution of inflammation and repair as a necessary adjunctive step to reach this goal. We explore the roles of inflammatory cell apoptosis and efferocytosis to promote resolution, the new knowledge of gut monocyte-macrophage populations and their secreted prorepair mediators, and the processes of gut epithelial repair and regeneration to bridge this gap. We discuss the need and rationale for this vision and the tangible steps toward integrating proresolution therapies in IBD.


2021 ◽  
Vol 22 (5) ◽  
pp. 2645
Author(s):  
Dinh Nam Tran ◽  
Seon Myeong Go ◽  
Seon-Mi Park ◽  
Eui-Man Jung ◽  
Eui-Bae Jeung

Inflammatory bowel diseases (IBDs) comprises a range of chronic inflammatory conditions of the intestinal tract. The incidence and prevalence of IBDs are increasing worldwide, but the precise etiology of these diseases is not completely understood. Calcium signaling plays a regulatory role in cellular proliferation. Nckx3, a potassium-dependent Na+/Ca2+ exchanger, is not only expressed in the brain but also in the aortic, uterine, and intestinal tissues, which contain abundant smooth muscle cells. This study investigated the role of Nckx3 in intestinal inflammation. Microarray analyses revealed the upregulation of the innate immune response-associated genes in the duodenum of Nckx3 knockout (KO) mice. The Nckx3 KO mice also showed an increase in IBD- and tumorigenesis-related genes. Using dextran sodium sulfate (DSS)-induced experimental colitis mice models, the Nckx3 KO mice showed severe colitis. Furthermore, the pathways involving p53 and NF-κB signaling were significantly upregulated by the absence of Nckx3. Overall, Nckx3 plays a critical role in the innate immune and immune response and may be central to the pathogenesis of IBD.


Immunotherapy ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 565-575
Author(s):  
Ferdinando D’Amico ◽  
Gionata Fiorino ◽  
Laurent Peyrin-Biroulet ◽  
Silvio Danese

2019 ◽  
Vol 07 (08) ◽  
pp. E1018-E1026 ◽  
Author(s):  
Entcho Klenske ◽  
Raja Atreya ◽  
Arndt Hartmann ◽  
Sarah Fischer ◽  
Simon Hirschmann ◽  
...  

Abstract Background and study aims Apart from mucosal healing as an established treatment goal in inflammatory bowel diseases (IBD), recent evidence suggests that histologic healing may become another key prognostic parameter in IBD patients. We aimed to evaluate whether magnification endoscopy with optical chromoendoscopy can accurately assess histologic inflammation in IBD patients. Patients and methods In this prospective study, 82 patients with IBD (30 UC, 52 CD) were included. In all patients, magnification endoscopy in conjunction with optical chromoendoscopy was performed and rated on a novel magnification endoscopy score by three independent endoscopists. Targeted biopsies of the imaged areas were obtained and results were compared against two histological scores in UC (Robarts Histopathology Index, RHI; Nancy Histology Index, NHI) and one score in CD (modified Riley index, mRI). Moreover, interobserver agreement was calculated. Results Magnification endoscopy showed strong correlation with histopathologic scoring in both UC (RHI: r = 0.83, NHI: r = 0.78, P < 0.05) and CD (mRI: r = 0.74, P < 0.05) with high accuracy, sensitivity, and specificity. Further, 25 % of patients with mucosal healing on standard endoscopy showed signs of microinflammation on magnification endoscopy with optical chromoendoscopy, while none of the patients with mucosal and vascular healing under magnification endoscopy with optical chromoendoscopy exhibited microscopic inflammation. Interobserver agreement for grading intestinal inflammation by magnification endoscopy with optical chromoendoscopy was substantial (κ > 0.7). Conclusion Magnification endoscopy in combination with optical chromoendoscopy shows strong correlation with histologic inflammation in patients with IBD. This approach has potential to reduce physical biopsies for monitoring of inflammatory activity in patients with IBD during colonoscopy.


2015 ◽  
Vol 21 (1) ◽  
pp. 198-207 ◽  
Author(s):  
Annaïg Lan ◽  
François Blachier ◽  
Robert Benamouzig ◽  
Martin Beaumont ◽  
Christophe Barrat ◽  
...  

2012 ◽  
Vol 6 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Jun Kato ◽  
Sakiko Hiraoka ◽  
Asuka Nakarai ◽  
Masao Ichinose

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