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Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency

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Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency. / Kezic, Sanja; O'Regan, Grainne M.; Lutter, Rene; Jakasa, Ivone; Koster, Ellen S.; Saunders, Sean; Caspers, Peter; Kemperman, Patrick M. J. H.; Puppels, Gerwin J.; Sandilands, Aileen; Chen, Huijia; Campbell, Linda E.; Kroboth, Karin; Watson, Rosemarie; Fallon, Padraic G.; McLean, W. H. Irwin; Irvine, Alan D.

In: Journal of Allergy and Clinical Immunology, Vol. 129, No. 4, 04.2012, p. 1031-U542.

Research output: Contribution to journalArticle

Harvard

Kezic, S, O'Regan, GM, Lutter, R, Jakasa, I, Koster, ES, Saunders, S, Caspers, P, Kemperman, PMJH, Puppels, GJ, Sandilands, A, Chen, H, Campbell, LE, Kroboth, K, Watson, R, Fallon, PG, McLean, WHI & Irvine, AD 2012, 'Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency' Journal of Allergy and Clinical Immunology, vol 129, no. 4, pp. 1031-U542.

APA

Kezic, S., O'Regan, G. M., Lutter, R., Jakasa, I., Koster, E. S., Saunders, S., Caspers, P., Kemperman, P. M. J. H., Puppels, G. J., Sandilands, A., Chen, H., Campbell, L. E., Kroboth, K., Watson, R., Fallon, P. G., McLean, W. H. I., & Irvine, A. D. (2012). Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency. Journal of Allergy and Clinical Immunology, 129(4), 1031-U542doi: 10.1016/j.jaci.2011.12.989

Vancouver

Kezic S, O'Regan GM, Lutter R, Jakasa I, Koster ES, Saunders S et al. Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency. Journal of Allergy and Clinical Immunology. 2012 Apr;129(4):1031-U542.

Author

Kezic, Sanja; O'Regan, Grainne M.; Lutter, Rene; Jakasa, Ivone; Koster, Ellen S.; Saunders, Sean; Caspers, Peter; Kemperman, Patrick M. J. H.; Puppels, Gerwin J.; Sandilands, Aileen; Chen, Huijia; Campbell, Linda E.; Kroboth, Karin; Watson, Rosemarie; Fallon, Padraic G.; McLean, W. H. Irwin; Irvine, Alan D. / Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency.

In: Journal of Allergy and Clinical Immunology, Vol. 129, No. 4, 04.2012, p. 1031-U542.

Research output: Contribution to journalArticle

Bibtex - Download

@article{1b9e1b0289b7480197bc5d9dc06b7a1b,
title = "Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency",
author = "Sanja Kezic and O'Regan, {Grainne M.} and Rene Lutter and Ivone Jakasa and Koster, {Ellen S.} and Sean Saunders and Peter Caspers and Kemperman, {Patrick M. J. H.} and Puppels, {Gerwin J.} and Aileen Sandilands and Huijia Chen and Campbell, {Linda E.} and Karin Kroboth and Rosemarie Watson and Fallon, {Padraic G.} and McLean, {W. H. Irwin} and Irvine, {Alan D.}",
year = "2012",
volume = "129",
number = "4",
pages = "1031--U542",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency

A1 - Kezic,Sanja

A1 - O'Regan,Grainne M.

A1 - Lutter,Rene

A1 - Jakasa,Ivone

A1 - Koster,Ellen S.

A1 - Saunders,Sean

A1 - Caspers,Peter

A1 - Kemperman,Patrick M. J. H.

A1 - Puppels,Gerwin J.

A1 - Sandilands,Aileen

A1 - Chen,Huijia

A1 - Campbell,Linda E.

A1 - Kroboth,Karin

A1 - Watson,Rosemarie

A1 - Fallon,Padraic G.

A1 - McLean,W. H. Irwin

A1 - Irvine,Alan D.

AU - Kezic,Sanja

AU - O'Regan,Grainne M.

AU - Lutter,Rene

AU - Jakasa,Ivone

AU - Koster,Ellen S.

AU - Saunders,Sean

AU - Caspers,Peter

AU - Kemperman,Patrick M. J. H.

AU - Puppels,Gerwin J.

AU - Sandilands,Aileen

AU - Chen,Huijia

AU - Campbell,Linda E.

AU - Kroboth,Karin

AU - Watson,Rosemarie

AU - Fallon,Padraic G.

AU - McLean,W. H. Irwin

AU - Irvine,Alan D.

PY - 2012/4

Y1 - 2012/4

N2 - <p>Background: Filaggrin (FLG) mutations result in reduced stratum corneum (SC) natural moisturizing factor (NMF) components and consequent increased SC pH. Because higher pH activates SC protease activity, we hypothesized an enhanced release of proinflammatory IL-1 cytokines from corneocytes in patients with atopic dermatitis (AD) with FLG mutations (AD(FLG)) compared with that seen in patients with AD without these mutations (AD(NON-FLG)).</p><p>Objectives: We sought to investigate SC IL-1 cytokine profiles in the uninvolved skin of controls and patients with AD(FLG) versus patients with AD(NON-FLG). We also sought to examine the same profiles in a murine model of filaggrin deficiency (Flg(ft)/Flg(ft) [Flg(delAPfal)] mice).</p><p>Methods: One hundred thirty-seven patients were studied. NMF levels were ascertained using confocal Raman spectroscopy; transepidermal water loss and skin surface pH were measured. IL-1 alpha, IL-1 beta, IL-18, IL-1 receptor antagonist (IL-1RA), and IL-8 levels were determined in SC tape strips from 93 patients. All subjects were screened for 9 FLG mutations. Flg(ft)/Flg(ft) (Flg(delAPfal)) mice, separated from maFlg(ft)/maFlg(ft) (flaky tail) mice, were used for the preparation and culture of primary murine keratinocytes and as a source of murine skin. RT-PCR was performed using primers specific for murine IL-1 alpha, IL-1 beta, and IL-1RA.</p><p>Results: SC IL-1 levels were increased in patients with AD(FLG); these levels were inversely correlated with NMF levels. NMF values were also inversely correlated with skin surface pH. Skin and keratinocytes from Flg(ft)/Flg(ft) mice had upregulated expression of IL-1 beta and IL-1RA mRNA.</p><p>Conclusions: AD(FLG) is associated with an increased SC IL-1 cytokine profile; this profile is also seen in a murine homologue of filaggrin deficiency. These findings might have importance in understanding the influence of FLG mutations on the inflammasome in the pathogenesis of AD and help individualize therapeutic approaches. (J Allergy Clin Immunol 2012;129:1031-9.)</p>

AB - <p>Background: Filaggrin (FLG) mutations result in reduced stratum corneum (SC) natural moisturizing factor (NMF) components and consequent increased SC pH. Because higher pH activates SC protease activity, we hypothesized an enhanced release of proinflammatory IL-1 cytokines from corneocytes in patients with atopic dermatitis (AD) with FLG mutations (AD(FLG)) compared with that seen in patients with AD without these mutations (AD(NON-FLG)).</p><p>Objectives: We sought to investigate SC IL-1 cytokine profiles in the uninvolved skin of controls and patients with AD(FLG) versus patients with AD(NON-FLG). We also sought to examine the same profiles in a murine model of filaggrin deficiency (Flg(ft)/Flg(ft) [Flg(delAPfal)] mice).</p><p>Methods: One hundred thirty-seven patients were studied. NMF levels were ascertained using confocal Raman spectroscopy; transepidermal water loss and skin surface pH were measured. IL-1 alpha, IL-1 beta, IL-18, IL-1 receptor antagonist (IL-1RA), and IL-8 levels were determined in SC tape strips from 93 patients. All subjects were screened for 9 FLG mutations. Flg(ft)/Flg(ft) (Flg(delAPfal)) mice, separated from maFlg(ft)/maFlg(ft) (flaky tail) mice, were used for the preparation and culture of primary murine keratinocytes and as a source of murine skin. RT-PCR was performed using primers specific for murine IL-1 alpha, IL-1 beta, and IL-1RA.</p><p>Results: SC IL-1 levels were increased in patients with AD(FLG); these levels were inversely correlated with NMF levels. NMF values were also inversely correlated with skin surface pH. Skin and keratinocytes from Flg(ft)/Flg(ft) mice had upregulated expression of IL-1 beta and IL-1RA mRNA.</p><p>Conclusions: AD(FLG) is associated with an increased SC IL-1 cytokine profile; this profile is also seen in a murine homologue of filaggrin deficiency. These findings might have importance in understanding the influence of FLG mutations on the inflammasome in the pathogenesis of AD and help individualize therapeutic approaches. (J Allergy Clin Immunol 2012;129:1031-9.)</p>

U2 - 10.1016/j.jaci.2011.12.989

DO - 10.1016/j.jaci.2011.12.989

M1 - Article

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 4

VL - 129

SP - 1031-U542

ER -

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