Enteroglial-derived S100B protein integrates bacteria-induced Toll-like receptor signalling in human enteric glial cells

Turco, Fabio; Sarnelli, Giovanni; Cirillo, Carla; Palumbo, Ilaria; Giorgi, F. De; D’Alessandro, Alessandra; Cammarota, Marcella; Giuliano, Mariateresa; Cuomo, Rosario

doi:10.1136/gutjnl-2012-302090

Cited by 150 publications

(191 citation statements)

References 45 publications

(64 reference statements)

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“…S100B targeting has already been tested in other disease models with promising results. In fact, pentamidine, a S100B inhibitor, reduces S100B and RAGE expression in an animal model of Alzheimer's disease, with consequent reduction of pro-inflammatory milieu in the hippocampus [68]. Other potential therapeutic strategies may be the use of specific RAGE antibodies to prevent S100B binding, small molecules or anti-S100B aptamers [69,70].…”

Section: Discussionmentioning

confidence: 98%

S100B as a Potential Biomarker and Therapeutic Target in Multiple Sclerosis

et al. 2015

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Multiple sclerosis (MS) pathology is characterized by neuroinflammation and demyelination. Recently, the inflammatory molecule S100B was identified in cerebrospinal fluid (CSF) and serum of MS patients. Although seen as an astrogliosis marker, lower/physiological levels of S100B are involved in oligodendrocyte differentiation/maturation. Nevertheless, increased S100B levels released upon injury may induce glial reactivity and oligodendrocyte demise, exacerbating tissue damage during an MS episode or delaying the following remyelination. Here, we aimed to unravel the functional role of S100B in the pathogenesis of MS. Elevated S100B levels were detected in the CSF of relapsing-remitting MS patients at diagnosis. Active demyelinating MS lesions showed increased expression of S100B and its receptor, the receptor for advanced glycation end products (RAGE), in the lesion area, while chronic active lesions displayed increased S100B in demyelinated areas with lower expression of RAGE in the rim. Interestingly, reactive astrocytes were identified as the predominant cellular source of S100B, whereas RAGE was expressed by activated microglia/macrophages. Using an ex vivo demyelinating model, cerebral organotypic slice cultures treated with lysophosphatidylcholine (LPC), we observed a marked elevation of S100B upon demyelination, which co-localized mostly with astrocytes. Inhibition of S100B action using a directed antibody reduced LPC-induced demyelination, prevented astrocyte reactivity and abrogated the expression of inflammatory and inflammasome-related molecules. Overall, high S100B expression in MS patient samples suggests its usefulness as a diagnostic biomarker for MS, while the beneficial outcome of its inhibition in our demyelinating model indicates S100B as an emerging therapeutic target in MS.

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Section: Discussionmentioning

confidence: 98%

S100B as a Potential Biomarker and Therapeutic Target in Multiple Sclerosis

et al. 2015

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“…S100␤ is constitutively expressed by EGC and seems to play an important role in IBD. It has been demonstrated that immunostaining of s100 is increased in rectal specimen of patients suffering from UC compared with healthy controls and an upregulation of s100␤ is accompanied by enhanced mucosal NO levels similar to mucosa from Crohn patients (10,57). EGC share more similarities with astrocytes in the central nervous system than with Schwann cells of the peripheral nervous system (15,29).…”

Section: Effects Of Enteric Glial Cells On Intestinal Epithelial Barrmentioning

confidence: 99%

The glial cell-line derived neurotrophic factor: a novel regulator of intestinal barrier function in health and disease

Meir

Flemming

Burkard

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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Regulation of the intestinal epithelial barrier is a differentiated process, which is profoundly deranged in inflammatory bowel diseases. Recent data provide evidence that the glial cell line-derived neurotrophic factor (GDNF) is critically involved in intestinal epithelial wound healing and barrier maturation and exerts antiapoptotic effects under certain conditions. Furthermore, not only the enteric nervous system, but also enterocytes synthesize GDNF in significant amounts, which points to a potential para- or autocrine signaling loop between enterocytes. Apart from direct effects of GDNF on enterocytes, an immunomodulatory role of this protein has been previously assumed because of a significant reduction of inflammation in a model of chronic inflammatory bowel disease after application of GDNF. In this review we summarize the current knowledge of GDNF on intestinal epithelial barrier regulation and discuss the novel role for GDNF as a regulator of intestinal barrier functions in health and disease.

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“…It has been proposed that the gliaspecific protein S100β is a pro-inflammatory mediator acting via the receptor for advanced-glycation end products) to increase production of NO in the mucosa (84,85). Furthermore, upon bacterial stimulation, EGCs upregulate expression of MHC class II, which suggests that they actively respond to the colonization of the gut lumen by microbiota and participate in antigen presentation to the adaptive immune system (86). In adult mice, lineage-tracing experiments under conditions of acute neuronal loss after chemical injury demonstrated that EGCs have the capacity to transdifferentiate into neurons in vivo.…”

Section: Microbiota Influence On Ens Developmentmentioning

confidence: 99%