Yin-Yang of IL-33 in Human Skin Mast Cells: Reduced Degranulation, but Augmented Histamine Synthesis through p38 Activation

Mast cells (MCs) are the principal effector cells of IgE-mediated allergy. IL-33 is released by resident skin cells as alarmin upon tissue damage or allergen contact. Owing to their pronounced receptor expression, MCs are important targets of IL-33 action, but consequences for skin MCs are ill-defin...

Full description

Saved in:
Bibliographic Details
Published in:Journal of investigative dermatology Vol. 139; no. 7; p. 1516
Main Authors: Babina, Magda, Wang, Zhao, Franke, Kristin, Guhl, Sven, Artuc, Metin, Zuberbier, Torsten
Format: Journal Article
Language:English
Published: United States 01.07.2019
Subjects:
Cell Cycle
Cell Degranulation
Cells, Cultured
Histamine - biosynthesis
Histidine Decarboxylase - metabolism
Humans
Hypersensitivity - immunology
Immunoglobulin E - metabolism
Inflammation - immunology
Interleukin-33 - metabolism
Mast Cells - metabolism
Mast Cells - pathology
p38 Mitogen-Activated Protein Kinases - genetics
p38 Mitogen-Activated Protein Kinases - metabolism
Receptors, IgE - metabolism
RNA Interference
Skin - pathology
Skin Diseases - immunology
Yin-Yang
ISSN:1523-1747, 1523-1747
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Abstract Mast cells (MCs) are the principal effector cells of IgE-mediated allergy. IL-33 is released by resident skin cells as alarmin upon tissue damage or allergen contact. Owing to their pronounced receptor expression, MCs are important targets of IL-33 action, but consequences for skin MCs are ill-defined, especially upon chronic exposure to IL-33. Mimicking the inflammatory milieu of skin disorders, we found that persistent exposure to IL-33 (over a 5-week period) strengthened skin MC numbers through accelerated cell-cycle progression and restriction of apoptosis. Conversely, IL-33 attenuated degranulation and FcεRI expression, potentially as a feedback to chronic "alarmin" exposure. Interestingly, the negative impact on histamine release was counterbalanced by amplified histamine production. Considering the clinical significance of histamine and scarce information on its regulation, we explored the molecular underpinnings. IL-33 induced swift phosphorylation of p38 and JNK (but not of ERK1/2 or AKT), and stimulated histidine decarboxylase expression. Combining pharmacological inhibition and kinase elimination by Accell-facilitated RNA interference in skin MCs revealed a p38-dependent, but JNK-independent mechanism. Collectively, IL-33 exerts multifaceted effects on cutaneous MCs at a post-maturation stage. The IL-33-skin MC axis may contribute to and balance inflammation in chronic skin disorders.
AbstractList Mast cells (MCs) are the principal effector cells of IgE-mediated allergy. IL-33 is released by resident skin cells as alarmin upon tissue damage or allergen contact. Owing to their pronounced receptor expression, MCs are important targets of IL-33 action, but consequences for skin MCs are ill-defined, especially upon chronic exposure to IL-33. Mimicking the inflammatory milieu of skin disorders, we found that persistent exposure to IL-33 (over a 5-week period) strengthened skin MC numbers through accelerated cell-cycle progression and restriction of apoptosis. Conversely, IL-33 attenuated degranulation and FcεRI expression, potentially as a feedback to chronic "alarmin" exposure. Interestingly, the negative impact on histamine release was counterbalanced by amplified histamine production. Considering the clinical significance of histamine and scarce information on its regulation, we explored the molecular underpinnings. IL-33 induced swift phosphorylation of p38 and JNK (but not of ERK1/2 or AKT), and stimulated histidine decarboxylase expression. Combining pharmacological inhibition and kinase elimination by Accell-facilitated RNA interference in skin MCs revealed a p38-dependent, but JNK-independent mechanism. Collectively, IL-33 exerts multifaceted effects on cutaneous MCs at a post-maturation stage. The IL-33-skin MC axis may contribute to and balance inflammation in chronic skin disorders.
Mast cells (MCs) are the principal effector cells of IgE-mediated allergy. IL-33 is released by resident skin cells as alarmin upon tissue damage or allergen contact. Owing to their pronounced receptor expression, MCs are important targets of IL-33 action, but consequences for skin MCs are ill-defined, especially upon chronic exposure to IL-33. Mimicking the inflammatory milieu of skin disorders, we found that persistent exposure to IL-33 (over a 5-week period) strengthened skin MC numbers through accelerated cell-cycle progression and restriction of apoptosis. Conversely, IL-33 attenuated degranulation and FcεRI expression, potentially as a feedback to chronic "alarmin" exposure. Interestingly, the negative impact on histamine release was counterbalanced by amplified histamine production. Considering the clinical significance of histamine and scarce information on its regulation, we explored the molecular underpinnings. IL-33 induced swift phosphorylation of p38 and JNK (but not of ERK1/2 or AKT), and stimulated histidine decarboxylase expression. Combining pharmacological inhibition and kinase elimination by Accell-facilitated RNA interference in skin MCs revealed a p38-dependent, but JNK-independent mechanism. Collectively, IL-33 exerts multifaceted effects on cutaneous MCs at a post-maturation stage. The IL-33-skin MC axis may contribute to and balance inflammation in chronic skin disorders.Mast cells (MCs) are the principal effector cells of IgE-mediated allergy. IL-33 is released by resident skin cells as alarmin upon tissue damage or allergen contact. Owing to their pronounced receptor expression, MCs are important targets of IL-33 action, but consequences for skin MCs are ill-defined, especially upon chronic exposure to IL-33. Mimicking the inflammatory milieu of skin disorders, we found that persistent exposure to IL-33 (over a 5-week period) strengthened skin MC numbers through accelerated cell-cycle progression and restriction of apoptosis. Conversely, IL-33 attenuated degranulation and FcεRI expression, potentially as a feedback to chronic "alarmin" exposure. Interestingly, the negative impact on histamine release was counterbalanced by amplified histamine production. Considering the clinical significance of histamine and scarce information on its regulation, we explored the molecular underpinnings. IL-33 induced swift phosphorylation of p38 and JNK (but not of ERK1/2 or AKT), and stimulated histidine decarboxylase expression. Combining pharmacological inhibition and kinase elimination by Accell-facilitated RNA interference in skin MCs revealed a p38-dependent, but JNK-independent mechanism. Collectively, IL-33 exerts multifaceted effects on cutaneous MCs at a post-maturation stage. The IL-33-skin MC axis may contribute to and balance inflammation in chronic skin disorders.
Author Guhl, Sven
Artuc, Metin
Wang, Zhao
Zuberbier, Torsten
Franke, Kristin
Babina, Magda
Author_xml – sequence: 1
  givenname: Magda
  surname: Babina
  fullname: Babina, Magda
  email: magda.babina@charite.de
  organization: Department of Dermatology, Venereology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany. Electronic address: magda.babina@charite.de
– sequence: 2
  givenname: Zhao
  surname: Wang
  fullname: Wang, Zhao
  organization: Department of Dermatology, Venereology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany
– sequence: 3
  givenname: Kristin
  surname: Franke
  fullname: Franke, Kristin
  organization: Department of Dermatology, Venereology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany
– sequence: 4
  givenname: Sven
  surname: Guhl
  fullname: Guhl, Sven
  organization: Department of Dermatology, Venereology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany
– sequence: 5
  givenname: Metin
  surname: Artuc
  fullname: Artuc, Metin
  organization: Department of Dermatology, Venereology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany
– sequence: 6
  givenname: Torsten
  surname: Zuberbier
  fullname: Zuberbier, Torsten
  organization: Department of Dermatology, Venereology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30684550$$D View this record in MEDLINE/PubMed
BookMark eNpNkEtLw0AUhQep2If-ADcySxcmziszibtSHy1UBKuLrsIkmaRTk0mbmRGKf96gFYQL98D9zoFzx2BgWqMAuMQoxAjz22241UVIEE5ChPuhJ2CEI0IDLJgY_NNDMLZ2i3oPi-IzMKSIxyyK0Ah8rbUJ1tJUsC3hYhlQCrWBc99IA1cfvXyW1sGZqmt7B19V4XNVwHtVddL4WjrdmhuYeQenvmqUcf1xrq2TjTYKrg7GbZTVFrpN1_pqA3c0htPc6c8f5zk4LWVt1cVxT8D748PbbB4sX54Ws-kyyBlOXFBgUZZCZCpjJC855yinJGacCE4KIbDkhSRllktMaYmEooT2gJJJzKSIY0Qm4Po3d9e1e6-sSxtt876SNKr1NiVYJAwxwkmPXh1RnzWqSHedbmR3SP8eRr4BD6purA
CitedBy_id crossref_primary_10_1111_exd_14182
crossref_primary_10_1073_pnas_1906817116
crossref_primary_10_3390_cells10010102
crossref_primary_10_3390_cells8080829
crossref_primary_10_3390_cells10010145
crossref_primary_10_3390_molecules25235580
crossref_primary_10_3390_cells13201681
crossref_primary_10_3390_ijms24044135
crossref_primary_10_3390_ijms252313050
crossref_primary_10_1111_all_14881
crossref_primary_10_1111_all_16620
crossref_primary_10_1097_itx_0000000000000032
crossref_primary_10_3390_ijms22094589
crossref_primary_10_3389_fimmu_2022_876515
crossref_primary_10_3390_cells13010098
crossref_primary_10_1016_j_jid_2021_07_153
crossref_primary_10_3389_fimmu_2022_861545
crossref_primary_10_3389_fimmu_2023_1207249
crossref_primary_10_3390_cells12232700
crossref_primary_10_3390_cells11060953
crossref_primary_10_3389_fimmu_2023_1151754
crossref_primary_10_1016_j_heliyon_2023_e13290
crossref_primary_10_12688_f1000research_22037_1
crossref_primary_10_1016_j_jaci_2022_01_030
crossref_primary_10_1016_j_jid_2020_09_017
crossref_primary_10_1016_j_jid_2024_10_593
crossref_primary_10_3390_ijms241612975
crossref_primary_10_1007_s00011_023_01699_y
crossref_primary_10_3390_cells8040341
crossref_primary_10_3390_ijms22073580
crossref_primary_10_3389_fimmu_2020_615236
crossref_primary_10_3390_cells12091306
crossref_primary_10_3389_fimmu_2021_804812
crossref_primary_10_3390_cells10050986
crossref_primary_10_1016_j_jaci_2020_08_027
crossref_primary_10_1016_j_radmp_2025_09_005
crossref_primary_10_3390_cells13010042
crossref_primary_10_1038_s41419_023_06139_7
crossref_primary_10_1038_s41598_019_54878_5
crossref_primary_10_3390_ijms21020464
crossref_primary_10_3390_biom15091224
ContentType Journal Article
Copyright Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Copyright_xml – notice: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
DBID CGR
CUY
CVF
ECM
EIF
NPM
7X8
DOI 10.1016/j.jid.2019.01.013
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
MEDLINE - Academic
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
MEDLINE - Academic
DatabaseTitleList MEDLINE
MEDLINE - Academic
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: 7X8
  name: MEDLINE - Academic
  url: https://search.proquest.com/medline
  sourceTypes: Aggregation Database
DeliveryMethod no_fulltext_linktorsrc
Discipline Medicine
EISSN 1523-1747
ExternalDocumentID 30684550
Genre Research Support, Non-U.S. Gov't
Journal Article
GroupedDBID ---
--K
.55
.GJ
0R~
0SF
1B1
29K
2WC
36B
3O-
3V.
4.4
457
53G
5GY
5RE
5VS
6I.
7X7
88E
8AO
8FI
8FJ
8R4
8R5
AACTN
AAEDW
AAFTH
AALRI
AAXUO
ABAWZ
ABJNI
ABLJU
ABMAC
ABUWG
ABVKL
ACGFO
ACGFS
ACPRK
ADBBV
ADEZE
ADFRT
ADVLN
AENEX
AEXQZ
AFEBI
AFETI
AFFNX
AFJKZ
AFKRA
AFTJW
AGHFR
AHMBA
AI.
AITUG
AKRWK
ALIPV
ALMA_UNASSIGNED_HOLDINGS
AMRAJ
BAWUL
BENPR
BFHJK
BPHCQ
BVXVI
CAG
CCPQU
CGR
COF
CS3
CUY
CVF
D-I
DIK
E3Z
EBS
ECM
EIF
EJD
F5P
FDB
FRP
FYUFA
GX1
HMCUK
HZ~
IH2
IHE
J5H
JSO
KQ8
L7B
LH4
LW6
M1P
M41
MVM
NCXOZ
NPM
NQ-
O9-
OK1
P2P
PKN
PQQKQ
PROAC
PSQYO
Q2X
R9-
RIG
RNS
ROL
RPZ
SSZ
TR2
UKHRP
VH1
W2D
X7M
Y6R
YFH
YOC
YUY
ZGI
7X8
AAYWO
ACVFH
ADCNI
AEUPX
AFPUW
AIGII
AKBMS
AKYEP
EFKBS
ID FETCH-LOGICAL-c419t-d17ff77beb42cf6660c328462762d771a6da2fbca133f07e323c32ea984a78802
IEDL.DBID 7X8
ISICitedReferencesCount 40
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000472234100025&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 1523-1747
IngestDate Sun Nov 09 14:10:57 EST 2025
Wed Feb 19 02:30:43 EST 2025
IsPeerReviewed true
IsScholarly true
Issue 7
Language English
License Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c419t-d17ff77beb42cf6660c328462762d771a6da2fbca133f07e323c32ea984a78802
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
PMID 30684550
PQID 2179404262
PQPubID 23479
ParticipantIDs proquest_miscellaneous_2179404262
pubmed_primary_30684550
PublicationCentury 2000
PublicationDate 2019-07-00
20190701
PublicationDateYYYYMMDD 2019-07-01
PublicationDate_xml – month: 07
  year: 2019
  text: 2019-07-00
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle Journal of investigative dermatology
PublicationTitleAlternate J Invest Dermatol
PublicationYear 2019
SSID ssj0016458
Score 2.4709601
Snippet Mast cells (MCs) are the principal effector cells of IgE-mediated allergy. IL-33 is released by resident skin cells as alarmin upon tissue damage or allergen...
SourceID proquest
pubmed
SourceType Aggregation Database
Index Database
StartPage 1516
SubjectTerms Cell Cycle
Cell Degranulation
Cells, Cultured
Histamine - biosynthesis
Histidine Decarboxylase - metabolism
Humans
Hypersensitivity - immunology
Immunoglobulin E - metabolism
Inflammation - immunology
Interleukin-33 - metabolism
Mast Cells - metabolism
Mast Cells - pathology
p38 Mitogen-Activated Protein Kinases - genetics
p38 Mitogen-Activated Protein Kinases - metabolism
Receptors, IgE - metabolism
RNA Interference
Skin - pathology
Skin Diseases - immunology
Yin-Yang
Title Yin-Yang of IL-33 in Human Skin Mast Cells: Reduced Degranulation, but Augmented Histamine Synthesis through p38 Activation
URI https://www.ncbi.nlm.nih.gov/pubmed/30684550
https://www.proquest.com/docview/2179404262
Volume 139
WOSCitedRecordID wos000472234100025&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText
inHoldings 1
isFullTextHit
isPrint
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1bS9xAGB2qW8QXrbbelU_wsUOTmZCZ-CKLurTQXRa1sPu0TOYiEZ1dTVaQ_vl-M5vFp0KhL3nJhTBz8t1zDiFnTFqr8lRRh-6aZmGAUOY5o4kslDISIcJcFJsQg4EcjYphW3Cr27HKpU2MhtpMdaiRf2MBOZE__WL2TINqVOiuthIaK6TDMZQJqBaj9y5CnkV9TnRRgYYzE8uuZpzveqgCUWhaRNbOoG7wtwgzepre5v--4yey0caY0F2AYot8sH6brPXbLvpn8ntceTpW_h6mDn78pJxD5SGW8yGIcUFf1Q1c2sfH-hxuArerNXAVWCV8K_b1Fcp5A935faT0NBDIRtQTPhxu3zyGlHVVQ6sABDMuoauXKmpfyK_e9d3ld9qKMFCdpUVDTSqcE6K0Zca0w2Qn0RxdWs7QihohUpUbxVypFSa7LhGWM44XWFXITGF6nbAdsuqn3u4RwGim4GjomdF4UhpVpkmics4SZ3Rp7D45XS7rBEEeOhfK2-m8nrwv7D7ZXezNZLZg45hgziPDr9kH_3D3IVkPW74Ytz0iHYefuD0mH_VrU9UvJxE9eBwM-38AWNrN3A
linkProvider ProQuest
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Yin-Yang+of+IL-33+in+Human+Skin+Mast+Cells%3A+Reduced+Degranulation%2C+but+Augmented+Histamine+Synthesis+through+p38+Activation&rft.jtitle=Journal+of+investigative+dermatology&rft.au=Babina%2C+Magda&rft.au=Wang%2C+Zhao&rft.au=Franke%2C+Kristin&rft.au=Guhl%2C+Sven&rft.date=2019-07-01&rft.issn=1523-1747&rft.eissn=1523-1747&rft.volume=139&rft.issue=7&rft.spage=1516&rft_id=info:doi/10.1016%2Fj.jid.2019.01.013&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1523-1747&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1523-1747&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1523-1747&client=summon