Interleukin-6 expression and regulation in rat enteric glial cells

Abstract

As yet, little is known about the function of the glia of the enteric nervous system (ENS), particularly in an immune-stimulated environment. This prompted us to study the potential of cultured enteroglial cells for cytokine synthesis and secretion. Jejunal myenteric plexus preparations from adult rats were enzymatically dissociated, and enteroglial cells were purified by complement-mediated cytolysis and grown in tissue culture. Cultured cells were stimulated with recombinant rat interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha, and IL-6 mRNA expression and secretion were assessed using RT-PCR and a bioassay, respectively. Stimulation with TNF-alpha did not affect IL-6 mRNA expression, whereas IL-1beta stimulated IL-6 mRNA and protein synthesis in a time- and concentration-dependent fashion. In contrast, IL-6 significantly and dose-dependently suppressed IL-6 mRNA expression. In summary, we have presented evidence that enteric glial cells are a potential source of IL-6 in the myenteric plexus and that cytokine production by enteric glial cells can be regulated by cytokines. These findings strongly support the contention that enteric glial cells act as immunomodulatory cells in the enteric nervous system.

Endogenous Prion Protein Attenuates Experimentally Induced Colitis

“…In addition, transcripts encoding IL-1␤ and IL-6, which were increased during DSS-induced colitis, have been shown to regulate cytokine production by enteric glial cells. 51 Although no differences were observed in basal intestinal permeability to FITC-conjugated dextran, the possibility remains that permeability differences might be present under inflammatory conditions. It has been proposed that PrP C may function as an antimicrobial peptide.…”

Role of enteric glial cells in inflammatory bowel disease

“…The divergent effects of type 1 (inflammatory) and type 2 (immunomodulatory) cytokines on EGC proliferation could have pathophysiological relevance since the nature of the cytokine profile during Crohn's disease, a human chronic IBD, shifts from a type 2 response in early lesions to a type 1 response in chronic lesions (Desreumaux et al, 1997). Moreover, Rü hl et al (2001a) have demonstrated that EGCs produce IL-6, similar to astrocytes (Van Wagoner and Benveniste, 1999). Indeed, in vitro stimulation of EGC cultures with IL-1␤ induces IL-6 mRNA expression, and stimulation of EGCs with IL-6 induces a dose-dependent suppression of IL-6 expression.…”

Mycobacterium aviumsubspeciesparatuberculosisinfects and multiplies in enteric glial cells

“…No gastrointestinal disorder has been reported linked to glial defect yet, most probably because subtle changes in glial function might be involved in the etiopathogenesis of enteric disorders. Crohn's disease with neuroinflammation and neurodegeneration components may be associated with EGC alteration [23][24][25] . Indeed EGC interact with enteric neurons, endothelial cells, immune cells and the intestinal epithelium; all these factors can contribute to the pathogenesis of Crohn's disease.…”

“…EGCs are an active part of an intestinal network system essential for a healthy and functional gut [23,26,27] . The role of EGC in Crohn's and other enteric diseases is not well studied and this is the first report that attempts to unravel interaction between an intestinal pathogen and EGC.…”

“…M. paratuberculosis for DNA extraction was grown in Mycobacteria Growth Indicator Tube (MGITl) medium supplemented with Mycobactin J and egg yolk. Murine enteric glial cells were previously isolated and characterized by Dr. Anne Ruhel [23] .…”