PAR2 Pepducin-Based Suppression of Inflammation and Itch in Atopic Dermatitis Models
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved..
PAR2 has been proposed to contribute to lesion formation and intense itch in atopic dermatitis. Here, we tested the ability of a cell-penetrating pepducin, PZ-235, to mitigate the potentially deleterious effects of PAR2 in models of atopic dermatitis. PZ-235 significantly inhibited PAR2-mediated expression of inflammatory factors NF-κB, TSLP, TNF-α, and differentiation marker K10 by 94%-98% (P < 0.001) in human keratinocytes and suppressed IL-4 and IL-13 by 68%-83% (P < 0.05) in mast cells. In delayed pepducin treatment models of oxazolone- and DNFB-induced dermatitis, PZ-235 significantly attenuated skin thickening by 43%-100% (P < 0.01) and leukocyte crusting by 57% (P < 0.05), and it inhibited ex vivo chemotaxis of leukocytes toward PAR2 agonists. Daily PZ-235 treatment of filaggrin-deficient mice exposed to dust mite allergens for 8 weeks significantly suppressed total leukocyte and T-cell infiltration by 50%-68%; epidermal thickness by 60%-77%; and skin thickening, scaling, excoriation, and total lesion severity score by 46%-56%. PZ-235 significantly reduced itching caused by wasp venom peptide degranulation of mast cells in mice by 51% (P < 0.05), which was comparable to the protective effects conferred by PAR2 deficiency. Taken together, these results suggest that a PAR2 pepducin may confer broad therapeutic benefits as a disease-modifying treatment for atopic dermatitis and itch.
| Errataetall: |
CommentIn: J Invest Dermatol. 2019 Feb;139(2):282-284. - PMID 30471839 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:139 |
|---|---|
| Enthalten in: |
The Journal of investigative dermatology - 139(2019), 2 vom: 01. Feb., Seite 412-421 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Barr, Travis P [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Cell-Penetrating Peptides |
|---|
| Anmerkungen: |
Date Completed 31.12.2019 Date Revised 04.12.2021 published: Print-Electronic CommentIn: J Invest Dermatol. 2019 Feb;139(2):282-284. - PMID 30471839 Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jid.2018.08.019 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM289226856 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM289226856 | ||
| 003 | DE-627 | ||
| 005 | 20231225062105.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jid.2018.08.019 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0964.xml |
| 035 | |a (DE-627)NLM289226856 | ||
| 035 | |a (NLM)30287285 | ||
| 035 | |a (PII)S0022-202X(18)32585-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Barr, Travis P |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a PAR2 Pepducin-Based Suppression of Inflammation and Itch in Atopic Dermatitis Models |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 31.12.2019 | ||
| 500 | |a Date Revised 04.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: J Invest Dermatol. 2019 Feb;139(2):282-284. - PMID 30471839 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a PAR2 has been proposed to contribute to lesion formation and intense itch in atopic dermatitis. Here, we tested the ability of a cell-penetrating pepducin, PZ-235, to mitigate the potentially deleterious effects of PAR2 in models of atopic dermatitis. PZ-235 significantly inhibited PAR2-mediated expression of inflammatory factors NF-κB, TSLP, TNF-α, and differentiation marker K10 by 94%-98% (P < 0.001) in human keratinocytes and suppressed IL-4 and IL-13 by 68%-83% (P < 0.05) in mast cells. In delayed pepducin treatment models of oxazolone- and DNFB-induced dermatitis, PZ-235 significantly attenuated skin thickening by 43%-100% (P < 0.01) and leukocyte crusting by 57% (P < 0.05), and it inhibited ex vivo chemotaxis of leukocytes toward PAR2 agonists. Daily PZ-235 treatment of filaggrin-deficient mice exposed to dust mite allergens for 8 weeks significantly suppressed total leukocyte and T-cell infiltration by 50%-68%; epidermal thickness by 60%-77%; and skin thickening, scaling, excoriation, and total lesion severity score by 46%-56%. PZ-235 significantly reduced itching caused by wasp venom peptide degranulation of mast cells in mice by 51% (P < 0.05), which was comparable to the protective effects conferred by PAR2 deficiency. Taken together, these results suggest that a PAR2 pepducin may confer broad therapeutic benefits as a disease-modifying treatment for atopic dermatitis and itch | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Cell-Penetrating Peptides |2 NLM | |
| 650 | 7 | |a F2RL1 protein, human |2 NLM | |
| 650 | 7 | |a F2rl1 protein, mouse |2 NLM | |
| 650 | 7 | |a FLG protein, human |2 NLM | |
| 650 | 7 | |a Filaggrin Proteins |2 NLM | |
| 650 | 7 | |a Receptor, PAR-2 |2 NLM | |
| 700 | 1 | |a Garzia, Chris |e verfasserin |4 aut | |
| 700 | 1 | |a Guha, Srijoy |e verfasserin |4 aut | |
| 700 | 1 | |a Fletcher, Elizabeth K |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Nga |e verfasserin |4 aut | |
| 700 | 1 | |a Wieschhaus, Adam J |e verfasserin |4 aut | |
| 700 | 1 | |a Ferrer, Lluis |e verfasserin |4 aut | |
| 700 | 1 | |a Covic, Lidija |e verfasserin |4 aut | |
| 700 | 1 | |a Kuliopulos, Athan |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of investigative dermatology |d 1945 |g 139(2019), 2 vom: 01. Feb., Seite 412-421 |w (DE-627)NLM000018597 |x 1523-1747 |7 nnns |
| 773 | 1 | 8 | |g volume:139 |g year:2019 |g number:2 |g day:01 |g month:02 |g pages:412-421 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jid.2018.08.019 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 139 |j 2019 |e 2 |b 01 |c 02 |h 412-421 | ||