Enteric Glia Cells Attenuate Cytomix-Induced Intestinal Epithelial Barrier Breakdown

Cheadle, Gerald; Costantini, Todd W.; Hageny, A.; Putnam, James G.; Lopez, Nicole; Eliceiri, Brian P.; Bansal, Vishal; Coimbra, Raul

doi:10.1016/j.jss.2011.11.272

Cited by 7 publications

(9 citation statements)

References 34 publications

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“…To block activation of protein kinase A (PKA) the inhibitor H89 (Calbiochem, Darmstadt, Germany) at 30 M was used. We mimicked inflammation-induced breakdown of the intestinal barrier with cytomix: 10 ng/ml TNF␣ (Biomol, Hamburg, Germany), 10 g/ml IL-1␤ (Sigma, St. Louis, MO), and 0.05 g/ml interferon-␥ (Millipore, Darmstadt, Germany), as reported previously (6). SB-202190 (Callbiochem) was used at 30 M to inhibit p38 mitogen-activated protein kinase (p38 MAPK).…”

Section: Methodsmentioning

confidence: 99%

Glial cell line-derived neurotrophic factor promotes barrier maturation and wound healing in intestinal epithelial cells in vitro

Meir

Flemming

Burkard

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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Recent data suggest that neurotrophic factors from the enteric nervous system are involved in intestinal epithelial barrier regulation. In this context the glial cell line-derived neurotrophic factor (GDNF) was shown to affect gut barrier properties in vivo directly or indirectly by largely undefined processes in a model of inflammatory bowel disease (IBD). We further investigated the potential role and mechanisms of GDNF in the regulation of intestinal barrier functions. Immunostaining of human gut specimen showed positive GDNF staining in enteric neuronal plexus and in enterocytes. In Western blots of the intestinal epithelial cell lines Caco2 and HT29B6, significant amounts of GDNF were detected, suggesting that enterocytes represent an additional source of GDNF. Application of recombinant GDNF on Caco2 and HT29B6 cells for 24 h resulted in significant epithelial barrier stabilization in monolayers with immature barrier functions. Wound-healing assays showed a significantly faster closure of the wounded areas after GDNF application. GDNF augmented cAMP levels and led to significant inactivation of p38 MAPK in immature cells. Activation of p38 MAPK signaling by SB-202190 mimicked GDNF-induced barrier maturation, whereas the p38 MAPK activator anisomycin blocked GDNF-induced effects. Increasing cAMP levels had adverse effects on barrier maturation, as revealed by permeability measurements. However, increased cAMP augmented the proliferation rate in Caco2 cells, and GDNF-induced proliferation of epithelial cells was abrogated by the PKA inhibitor H89. Our data show that enterocytes represent an additional source of GDNF synthesis. GDNF contributes to wound healing in a cAMP/PKA-dependent manner and promotes barrier maturation in immature enterocytes cells by inactivation of p38 MAPK signaling.

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Section: Methodsmentioning

confidence: 99%

Glial cell line-derived neurotrophic factor promotes barrier maturation and wound healing in intestinal epithelial cells in vitro

Meir

Flemming

Burkard

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…mechanism for this effect (58)(59)(60). Enteric glia express TLRs, and these are differentially upregulated in response to pathogenic and non-pathogenic bacteria (61,62).…”

Section: Role Of Enteric Glia In Brain Disordersmentioning

confidence: 99%

Emerging roles for enteric glia in gastrointestinal disorders

Sharkey¹

2015

J. Clin. Invest.

161

131

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“…30 Consistently, EGCs were shown to increase IEB resistance evoked by stressors such as bacteria, inflammatory mediators, or skin burn injuries. [31][32][33] Recent evidence suggests that EGCs could also mediate neuronal effects in a conceptually similar fashion to the cross talk between neurons, interstitial cells of Cajal, and smooth muscle cells. Indeed, vagal stimulation was reported to reinforce skin burn-induced disruption of the IEB.…”

Section: Role Of Egcs In the Control Of Non-neuronal Functionsmentioning

confidence: 99%