Critical role of map kinases in governing lymphocyte adhesion to and migration across microvasculature in inflammatory bowel disease (IBD)

AbstractThe Hedgehog (Hh) signalling pathway plays a critical role in the growth and patterning during embryonic development and maintenance of adult tissue homeostasis. Emerging data indicate that Hh signalling is implicated in the pathogenesis of inflammatory bowel disease (IBD). Current therapeutic treatments for IBD require optimisation, and novel effective drugs are warranted. Targeting the Hh signalling pathway may pave the way for successful IBD treatment. In this review, we introduce the molecular mechanisms underlying the Hh signalling pathway and its role in maintaining intestinal homeostasis. Then, we present interactions between the Hh signalling and other pathways involved in IBD and colitis-associated colorectal cancer (CAC), such as the Wnt and nuclear factor-kappa B (NF-κB) pathways. Furthermore, we summarise the latest research on Hh signalling associated with the occurrence and progression of IBD and CAC. Finally, we discuss the future directions for research on the role of Hh signalling in IBD pathogenesis and provide viewpoints on novel treatment options for IBD by targeting Hh signalling. An in-depth understanding of the complex role of Hh signalling in IBD pathogenesis will contribute to the development of new effective therapies for IBD patients.

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Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0808242105 ◽

2008 ◽

Vol 105 (46) ◽

pp. 17931-17936 ◽

Cited By ~ 38

Author(s):

Danyvid Olivares-Villagómez ◽

Yanice V. Mendez-Fernandez ◽

Vrajesh V. Parekh ◽

Saif Lalani ◽

Tiffaney L. Vincent ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Genetic Model ◽

Critical Role ◽

Intraepithelial Lymphocytes ◽

Lymphocyte Function ◽

Intestinal Epithelial ◽

Inflammatory Bowel

Intestinal intraepithelial lymphocytes (IEL) bear a partially activated phenotype that permits them to rapidly respond to antigenic insults. However, this phenotype also implies that IEL must be highly controlled to prevent misdirected immune reactions. It has been suggested that IEL are regulated through the interaction of the CD8αα homodimer with the thymus leukemia (TL) antigen expressed by intestinal epithelial cells. We have generated and characterized mice genetically-deficient in TL expression. Our findings show that TL expression has a critical role in maintaining IEL effector functions. Also, TL deficiency accelerated colitis in a genetic model of inflammatory bowel disease. These findings reveal an important regulatory role of TL in controlling IEL function and intestinal inflammation.

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S1636 The Critical Role of CXC Chemokine Ligand 16/Scavenger Receptor in the Pathogenesis of Inflammatory Bowel Disease

Gastroenterology ◽

10.1016/s0016-5085(09)61082-9 ◽

2009 ◽

Vol 136 (5) ◽

pp. A-239

Author(s):

Norimitsu Uza ◽

Hiroshi Nakase ◽

Tsutomu Chiba

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Critical Role ◽

Scavenger Receptor ◽

Cxc Chemokine ◽

Chemokine Ligand ◽

Inflammatory Bowel

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Critical role of Keratin 1 in maintaining epithelial barrier and correlation of its down-regulation with the progression of inflammatory bowel disease

Gene ◽

10.1016/j.gene.2017.01.015 ◽

2017 ◽

Vol 608 ◽

pp. 13-19 ◽

Cited By ~ 7

Author(s):

Xiangqian Dong ◽

Zichao Liu ◽

Danfeng Lan ◽

Junkun Niu ◽

Jiarong Miao ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Critical Role ◽

Epithelial Barrier ◽

Down Regulation ◽

Inflammatory Bowel ◽

Keratin 1

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CD147 Aggravated Inflammatory Bowel Disease by Triggering NF-κB-Mediated Pyroptosis

BioMed Research International ◽

10.1155/2020/5341247 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Zhaohui Xu ◽

Ruitao Liu ◽

Ling Huang ◽

Yuxin Xu ◽

Mingmin Su ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Therapeutic Strategy ◽

Critical Role ◽

Mucosal Barrier ◽

Intestinal Epithelial ◽

Cd147 Expression ◽

Barrier Defect ◽

Inflammatory Bowel

Background. Pyroptosis, a novel form of inflammatory programmed cell death, was recently found to be a cause of mucosal barrier defect. In our pervious study, CD147 expression was documented to increase in intestinal tissue of inflammatory bowel disease (IBD). Objective. The aim of this study was to determine the function of serum CD147 in pyroptosis. Methods. The study group consisted of 96 cases. The centration of CD147, IL-1β, and IL-18 levels in serum was assessed by ELISA. Real-time PCR and WB were performed to analyze the effect of CD147 on pyroptosis. Results. In this study, our results showed that CD147 induced cell pyroptosis in intestinal epithelial cells (IECs) by enhancement of IL-1β and IL-18 expression and secretion in IECs, which is attributed to activation of inflammasomes, including caspase-1 and GSDMD as well as GSDME, leading to aggregate inflammatory reaction. Mechanically, CD147 promoted phosphorylation of NF-κB p65 in IECs, while inhibition of NF-κB activity by the NF-κB inhibitor BAY11-7082 reversed the effect of CD147 on IL-1β and IL-18 secretion. Most importantly, serum CD147 level is slightly clinically correlated with IL-1β, but not IL-18 level. Conclusion. These findings revealed a critical role of CD147 in the patients with IBD, suggesting that blockade of CD147 may be a novel therapeutic strategy for the patients with IBD.

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