Cholinergic receptor activation on epithelia protects against cytokine-induced barrier dysfunction (2024)

Dhawan, S., Hiemstra, I. H., Verseijden, C., Hilbers, F. W., te Velde, A. A., Willemsen, L. E. M., Stap, J., den Haan, J. M., & de Jonge, W. J. (2015). Cholinergic receptor activation on epithelia protects against cytokine-induced barrier dysfunction. Acta Physiologica, 213(4), 846-859. https://doi.org/10.1111/apha.12469

Dhawan, S. ; Hiemstra, I. H. ; Verseijden, C. et al. / Cholinergic receptor activation on epithelia protects against cytokine-induced barrier dysfunction. In: Acta Physiologica. 2015 ; Vol. 213, No. 4. pp. 846-859.

@article{bfe2038265c2464c917bd80bcd9054ae,

title = "Cholinergic receptor activation on epithelia protects against cytokine-induced barrier dysfunction",

abstract = "Various types of cholinergic receptors are expressed on intestinal epithelia. Their function is not completely understood. We hypothesize that cholinergic receptor activation on epithelium may serve a protective function in cytokine-induced barrier dysfunction. Methods: The effect of cholinergic receptor activation on cellular barrier function in epithelial cells was assessed by measuring electrical impedance, and by determining para-cellular transport in transwell experiments. Cell lysates treated with cytokine and/or cholinergic agonists were analysed for cyto- and chemokine production, and tight junction (TJ) protein rearrangement was assessed. Primary colonic epithelial cells were isolated from surgically resected colon tissue of patients with inflammatory bowel disease. Results: IL-1β induced production of chemokines (CXCL-1, CXCL-10, IL-8, CCL-7) and led to a rearrangement of TJ proteins (occludin and ZO-1). This response was inhibited by pre-treatment with muscarinic, rather than nicotinic, acetylcholine receptor agonists. Treatment with IL-1β enhanced paracellular permeability (4kD dextran) and reduced impedance across the monolayer, which was counteracted by pre-incubation with acetylcholine, or muscarinic receptor agonist bethanechol. The protective effect of acetylcholine was antagonized by atropine, underscoring muscarinic receptor involvement. IL-1β induced transcription of myosin light chain kinase and phosphorylation of myosin light chain, and this cytokine-induced phosphorylation of MLC was inhibited by muscarinic receptor agonists. Furthermore, in epithelial cells from resection material of patients with Crohn's disease and ulcerative colitis, high expression of CXCL-8 was associated with a reduced choline acetyl transferase expression, suggesting an aberrant epithelial production of ACh in inflammatory context. Conclusion: Acetylcholine acts on muscarinic receptors on epithelial cells to maintain epithelial barrier function under inflammatory conditions.",

keywords = "Cholinergic receptors, Epithelial permeability, Interleukin-1 beta, Myosin light chain, Tight junction proteins",

author = "S. Dhawan and Hiemstra, {I. H.} and C. Verseijden and Hilbers, {F. W.} and {te Velde}, {A. A.} and Willemsen, {L. E.M.} and J. Stap and {den Haan}, {J. M.} and {de Jonge}, {W. J.}",

note = "Publisher Copyright: {\textcopyright} 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.",

year = "2015",

month = apr,

day = "1",

doi = "10.1111/apha.12469",

language = "English",

volume = "213",

pages = "846--859",

journal = "Acta Physiologica",

issn = "1748-1708",

publisher = "Wiley-Blackwell",

number = "4",

}

Dhawan, S, Hiemstra, IH, Verseijden, C, Hilbers, FW, te Velde, AA, Willemsen, LEM, Stap, J, den Haan, JM & de Jonge, WJ 2015, 'Cholinergic receptor activation on epithelia protects against cytokine-induced barrier dysfunction', Acta Physiologica, vol. 213, no. 4, pp. 846-859. https://doi.org/10.1111/apha.12469

Cholinergic receptor activation on epithelia protects against cytokine-induced barrier dysfunction. / Dhawan, S.; Hiemstra, I. H.; Verseijden, C. et al.
In: Acta Physiologica, Vol. 213, No. 4, 01.04.2015, p. 846-859.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Cholinergic receptor activation on epithelia protects against cytokine-induced barrier dysfunction

AU - Dhawan, S.

AU - Hiemstra, I. H.

AU - Verseijden, C.

AU - Hilbers, F. W.

AU - te Velde, A. A.

AU - Willemsen, L. E.M.

AU - Stap, J.

AU - den Haan, J. M.

AU - de Jonge, W. J.

N1 - Publisher Copyright:© 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Various types of cholinergic receptors are expressed on intestinal epithelia. Their function is not completely understood. We hypothesize that cholinergic receptor activation on epithelium may serve a protective function in cytokine-induced barrier dysfunction. Methods: The effect of cholinergic receptor activation on cellular barrier function in epithelial cells was assessed by measuring electrical impedance, and by determining para-cellular transport in transwell experiments. Cell lysates treated with cytokine and/or cholinergic agonists were analysed for cyto- and chemokine production, and tight junction (TJ) protein rearrangement was assessed. Primary colonic epithelial cells were isolated from surgically resected colon tissue of patients with inflammatory bowel disease. Results: IL-1β induced production of chemokines (CXCL-1, CXCL-10, IL-8, CCL-7) and led to a rearrangement of TJ proteins (occludin and ZO-1). This response was inhibited by pre-treatment with muscarinic, rather than nicotinic, acetylcholine receptor agonists. Treatment with IL-1β enhanced paracellular permeability (4kD dextran) and reduced impedance across the monolayer, which was counteracted by pre-incubation with acetylcholine, or muscarinic receptor agonist bethanechol. The protective effect of acetylcholine was antagonized by atropine, underscoring muscarinic receptor involvement. IL-1β induced transcription of myosin light chain kinase and phosphorylation of myosin light chain, and this cytokine-induced phosphorylation of MLC was inhibited by muscarinic receptor agonists. Furthermore, in epithelial cells from resection material of patients with Crohn's disease and ulcerative colitis, high expression of CXCL-8 was associated with a reduced choline acetyl transferase expression, suggesting an aberrant epithelial production of ACh in inflammatory context. Conclusion: Acetylcholine acts on muscarinic receptors on epithelial cells to maintain epithelial barrier function under inflammatory conditions.

AB - Various types of cholinergic receptors are expressed on intestinal epithelia. Their function is not completely understood. We hypothesize that cholinergic receptor activation on epithelium may serve a protective function in cytokine-induced barrier dysfunction. Methods: The effect of cholinergic receptor activation on cellular barrier function in epithelial cells was assessed by measuring electrical impedance, and by determining para-cellular transport in transwell experiments. Cell lysates treated with cytokine and/or cholinergic agonists were analysed for cyto- and chemokine production, and tight junction (TJ) protein rearrangement was assessed. Primary colonic epithelial cells were isolated from surgically resected colon tissue of patients with inflammatory bowel disease. Results: IL-1β induced production of chemokines (CXCL-1, CXCL-10, IL-8, CCL-7) and led to a rearrangement of TJ proteins (occludin and ZO-1). This response was inhibited by pre-treatment with muscarinic, rather than nicotinic, acetylcholine receptor agonists. Treatment with IL-1β enhanced paracellular permeability (4kD dextran) and reduced impedance across the monolayer, which was counteracted by pre-incubation with acetylcholine, or muscarinic receptor agonist bethanechol. The protective effect of acetylcholine was antagonized by atropine, underscoring muscarinic receptor involvement. IL-1β induced transcription of myosin light chain kinase and phosphorylation of myosin light chain, and this cytokine-induced phosphorylation of MLC was inhibited by muscarinic receptor agonists. Furthermore, in epithelial cells from resection material of patients with Crohn's disease and ulcerative colitis, high expression of CXCL-8 was associated with a reduced choline acetyl transferase expression, suggesting an aberrant epithelial production of ACh in inflammatory context. Conclusion: Acetylcholine acts on muscarinic receptors on epithelial cells to maintain epithelial barrier function under inflammatory conditions.

KW - Cholinergic receptors

KW - Epithelial permeability

KW - Interleukin-1 beta

KW - Myosin light chain

KW - Tight junction proteins

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U2 - 10.1111/apha.12469

DO - 10.1111/apha.12469

M3 - Article

C2 - 25683465

AN - SCOPUS:84924710199

SN - 1748-1708

VL - 213

SP - 846

EP - 859

JO - Acta Physiologica

JF - Acta Physiologica

IS - 4

ER -

Dhawan S, Hiemstra IH, Verseijden C, Hilbers FW, te Velde AA, Willemsen LEM et al. Cholinergic receptor activation on epithelia protects against cytokine-induced barrier dysfunction. Acta Physiologica. 2015 Apr 1;213(4):846-859. doi: 10.1111/apha.12469