Proinflammatory cytokines increase gild fibrillary acidic protein expression in enteric glia

von Boyen, G. B. T.; Steinkamp, M.; Reinshagen, M.; Schäfer, K. -H.; Adler, G.; Kirsch, J.
February 2004
Gut;Feb2004, Vol. 53 Issue 2, p222
Academic Journal
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 1β (IL-1β), interleukin 4 (IL-A), tumour necrosis factor α (TNF-α, and lipopolysaccharides (LPS) on cultured enteric glia. Methods: Dissected rat colon and cultured enteric glia cells were double labelled with anti-GEAP and anti- 5-100 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 (-) from GFAP+ glia subtypes in situ and in primary cultures. Incubation of cells with IL-1β, TNF-α, and LPS led to a significant increase in GFAP+ enteric glia while IL-4 had no effect on GFAP expression. After incubation with IL-1β, total intracellular GFAP of enteric glia cells was increased. Upregukition of GFAP+ enteric glia could also be observed after stimulation with IL-1β 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.


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