Download presentation
Presentation is loading. Please wait.
Published byEugenio Tommasi Modified over 6 years ago
1
IL36RN Mutations Affect Protein Expression and Function: A Basis for Genotype- Phenotype Correlation in Pustular Diseases Marie Tauber, Elodie Bal, Xue-Yuan Pei, Marine Madrange, Amel Khelil, Houria Sahel, Akila Zenati, Mohamed Makrelouf, Khaled Boubridaa, Amel Chiali, Naima Smahi, Farida Otsmane, Bakar Bouajar, Slaheddine Marrakchi, Hamida Turki, Emmanuelle Bourrat, Manuelle Viguier, Yamina Hamel, Hervé Bachelez, Asma Smahi Journal of Investigative Dermatology Volume 136, Issue 9, Pages (September 2016) DOI: /j.jid Copyright © 2016 The Authors Terms and Conditions
2
Figure 1 Pedigrees. (a) Pedigrees of studied families with mutations in the IL36RN gene. (b) Pedigrees of studied families without mutation in IL36RN. Generalized pustular psoriasis-affected and -unaffected individuals are represented with black and white symbols, respectively. Psoriasis vulgaris is indicated with an asterisk. IL36RN genotype is denoted under each subject. p.Gly141, p.Gly141MetfsX29; WT, wild-type. Journal of Investigative Dermatology , DOI: ( /j.jid ) Copyright © 2016 The Authors Terms and Conditions
3
Figure 2 Sequencing of the IL36RN gene (NM_173170). (a) The c.41C>A/p.Ser14X mutation and the c.420_426del/p.Gly141MetfsX29 deletion in affected patients compared with healthy control subjects. (b) Production of IL-8, assessed by means of ELISA, in monocytes supernatant and either LPS, IL-1β, or IL-36 cocktail ligands (α, β, and γ mixed together) stimulation. Under stimulation by the IL-36 cocktail ligands, there was a significantly higher production of IL-8 in all patients compared with control subjects (P < 0.01). IL-1β and LPS were used as positive controls. The results represent triplicate determination of a single experiment that is representative of a total of at least two similar experiments. LPS, lipopolysaccharide; NS, not stimulated. Journal of Investigative Dermatology , DOI: ( /j.jid ) Copyright © 2016 The Authors Terms and Conditions
4
Figure 3 Impact of IL36RN gene mutations on IL-36Ra protein expression and function. (a) Immunoblotting showing expression of IL-36Ra mutations after transfection in HEK293T cells. No expression was observed for p.Ser14X, p.Gly141MetfsX29, p.Leu27Pro, p.Arg10X, p.Glu94X, p.Thr123Arg, p.Thr123Met, and p.Pro76Leu mutations. IL-36Ra expression was reduced for p.His32Arg, p.Arg48Trp, and p.Ser113Leu and was almost unchanged for p.Arg102Trp and p.Lys35Arg variants compared with the wild type. (b) Results of NF-κB promoter reporter gene assay in HEK293T cells. The NF-κB activity induced by IL-36γ and IL-1Rrp2 transfection is strikingly reduced by the wild-type IL-36Ra and the p.Lys35Arg and p.Arg102Trp variants, and it is partially decreased in the cases of other IL-36Ra mutations. pcDNA (mammalian expression veactor/plasmid with the CMV promoter) are negative controls. The results represent triplicate determination of a single experiment that is representative of at least two similar experiments. *P < 0.01, ***P < ¶The result of the p.Leu27Pro mutation is representative of the results obtained for all null mutations (p.Ser14X, p.Gly141MetfsX29, p.Arg10X, p.Glu94X, p.Thr123Arg, p.Thr123Met, and p.Pro76Leu). p.G141, p.Gly141MetfsX29; WT, wild type. Journal of Investigative Dermatology , DOI: ( /j.jid ) Copyright © 2016 The Authors Terms and Conditions
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.