S100B protein in the gut: The evidence for enteroglial-sustained intestinal inflammation

Abstract

Glial cells in the gut represent the morphological and functional equivalent of astrocytes and microglia in the central nervous system (CNS). In recent years, the role of enteric glial cells (EGCs) has extended from that of simple nutritive support for enteric neurons to that of being pivotal participants in the regulation of inflammatory events in the gut. Similar to the CNS astrocytes, the EGCs physiologically express the S100B protein that exerts either trophic or toxic effects depending on its concentration in the extracellular milieu. In the CNS, S100B overexpression is responsible for the initiation of a gliotic reaction by the release of pro-inflammatory mediators, which may have a deleterious effect on neighboring cells. S100B-mediated pro-inflammatory effects are not limited to the brain: S100B overexpression is associated with the onset and maintenance of inflammation in the human gut too. In this review we describe the major features of EGCs and S100B protein occurring in intestinal inflammation deriving from such.

CD166/ALCAM Mediates Proinflammatory Effects of S100B in Delayed Type Hypersensitivity

“…1C). S100 proteins are known to elicit immune responses in diseases characterized by cross talk between adaptive and innate immune responses (37)(38)(39)(40)(41). Therefore, a search for structural homologs of RAGE was initiated by searching the PRODOM database, yielding a significant hit comparing the range from amino acid residues 1-250 of the mature RAGE protein with the PRODOM database entry PRO-DOM:3993.…”

Effects of Oxaliplatin Treatment on the Enteric Glial Cells and Neurons in the Mouse Ileum

“…55 In the gut, aberrant expression of s100β protein participates in the onset and progression of inflammatory status, orchestrating a wide range of proinflammatory pathways that are directly involved in intestinal inflammation. 27,28,42 Previous studies have reported increases in EGCderived s100β mRNA, protein expression, and secretion in the duodenum of patients with celiac disease and Crohn's disease, as well as in the rectal mucosa of ulcerative colitis patients. 27,42 The differences in GFAP and s100β functions may explain the opposite effects of oxaliplatin treatment on the expression of these proteins observed in our study.…”

“…41 A small, diffusible neurotrophin s100β is located in the cytoplasm or nucleus of cells in both nervous system and nonnervous system tissues. 28 The gut s100β protein, a small signaling diffusible Ca 2+ /Zn 2+ -binding protein, is specifically expressed by EGCs. 27,42 This protein regulates cytoskeletal structure and function and Ca 2+ homeostasis in the cytoplasm of glial cells.…”

“…22,25,26 EGCs can proliferate and be activated in response to injury and inflammation. 27,28 Previous studies have shown that in the CNS, astrocytes are sensitive to the platinum drug toxicity 29 and contribute to the development and persistence of chronic pain. 30,31 Glial cell inhibition in the CNS reduces oxaliplatin-induced pain.…”

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

“…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).…”