Proinflammatory cytokines increase glial fibrillary acidic protein expression in enteric glia

Abstract

Background: Enteric glia protect the integrity of the gut, as loss of enteric glial fibrillary acidic protein (GFAP) positive (+) glia leads to a haemorrhagic jejunoileitis. Crohn's disease (CD) and necrotising enterocolitis (NEC) show pathological changes in enteric glia. Therefore, factors controlling GFAP+ enteric glia are of great interest. The aim of the present study was to characterise enteric glia and determine the effect of interleukin 1b (IL-1b), interleukin 4 (IL-4), tumour necrosis factor a (TNF-a), and lipopolysaccharides (LPS) on cultured enteric glia. Methods: Dissected rat colon and cultured enteric glia cells were double labelled with anti-GFAP and anti-S-100 antibodies. For regulatory studies, enteric glia cells were treated with cytokines and LPS. Proliferation was assayed using bromodeoxyuridine (BrdU) and mitosis of enteric glia was blocked by demecolcine. Results: We were able to distinguish GFAP negative (2) from GFAP+ glia subtypes in situ and in primary cultures. Incubation of cells with IL-1b, TNF-a, and LPS led to a significant increase in GFAP+ enteric glia while IL-4 had no effect on GFAP expression. After incubation with IL-1b, total intracellular GFAP of enteric glia cells was increased. Upregulation of GFAP+ enteric glia could also be observed after stimulation with IL-1b on blocking mitosis. BrdU uptake in stimulated enteric glia showed no increased proliferation rate. Conclusions: Two different types of enteric glia based on GFAP expression exist in the gut. Proinflammatory cytokines and LPS cause a dramatic increase in GFAP+ enteric glia. This suggests that cytokines play an important role in controlling GFAP+ enteric glia which might in turn be involved in modulating the integrity of the bowel during inflammation.

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

“…In recent years it was consistently reported, that reduced levels of GDNF lead to morphological and functional abnormalities of IEB in mice comparable to the changes known in IBD (8,61,68). Conversely, it was shown that GNDF immunoreactivity was upregulated in experimental colitis and in specimen of patients with IBD, which was an effect predominately observed in enterocytes (52).…”

Phenotypic Polarization of Activated Astrocytes: The Critical Role of Lipocalin-2 in the Classical Inflammatory Activation of Astrocytes

“…The opposing roles of LPS/IFN-g and IL-4/IL-10 in the functional regulation of astrocytic phenotypes has been documented extensively. For instance, LPS led to a significant increase in GFAP expression in glia, but IL-4 had no effect (70), and although LPS and proinflammatory cytokines reduced levels of brain-derived neurotrophic factor in astrocytes, IL-4 increased them (71). Moreover, glucose use was increased in classically activated astrocytes, but it was attenuated by IL-10 (72).…”

Plasticity of Schwann cells and pericytes in response to islet injury in mice

“…In the enteric nervous system, increases in the expression of glial fibrillary acidic protein (GFAP) and proliferation of glial cells have also been reported in bowel inflammation such as ulcerative colitis [9][10][11][12]. As to the 'neuroendocrine' islet, it remains unclear whether similar reactive cellular responses occur in islet injuries, such as insulitis, in the progression of type 1 diabetes.…”