Steroid hormone catabolites activate the pyrin inflammasome through a non-canonical mechanism
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved..
The pyrin inflammasome acts as a guard of RhoA GTPases and is central to immune defenses against RhoA-manipulating pathogens. Pyrin activation proceeds in two steps. Yet, the second step is still poorly understood. Using cells constitutively activated for the pyrin step 1, a chemical screen identifies etiocholanolone and pregnanolone, two catabolites of testosterone and progesterone, acting at low concentrations as specific step 2 activators. High concentrations of these metabolites fully and rapidly activate pyrin, in a human specific, B30.2 domain-dependent manner and without inhibiting RhoA. Mutations in MEFV, encoding pyrin, cause two distinct autoinflammatory diseases pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND) and familial Mediterranean fever (FMF). Monocytes from PAAND patients, and to a lower extent from FMF patients, display increased responses to these metabolites. This study identifies an unconventional pyrin activation mechanism, indicates that endogenous steroid catabolites can drive autoinflammation, through the pyrin inflammasome, and explains the "steroid fever" described in the late 1950s upon steroid injection in humans.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
|---|---|
| Enthalten in: |
Cell reports - 41(2022), 2 vom: 11. Okt., Seite 111472 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Magnotti, Flora [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 14.10.2022 Date Revised 04.11.2022 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.celrep.2022.111472 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM347388930 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM347388930 | ||
| 003 | DE-627 | ||
| 005 | 20231226205406.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.celrep.2022.111472 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1157.xml |
| 035 | |a (DE-627)NLM347388930 | ||
| 035 | |a (NLM)36223753 | ||
| 035 | |a (PII)S2211-1247(22)01322-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Magnotti, Flora |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Steroid hormone catabolites activate the pyrin inflammasome through a non-canonical mechanism |
| 264 | 1 | |c 2022 | |
| 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 14.10.2022 | ||
| 500 | |a Date Revised 04.11.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a The pyrin inflammasome acts as a guard of RhoA GTPases and is central to immune defenses against RhoA-manipulating pathogens. Pyrin activation proceeds in two steps. Yet, the second step is still poorly understood. Using cells constitutively activated for the pyrin step 1, a chemical screen identifies etiocholanolone and pregnanolone, two catabolites of testosterone and progesterone, acting at low concentrations as specific step 2 activators. High concentrations of these metabolites fully and rapidly activate pyrin, in a human specific, B30.2 domain-dependent manner and without inhibiting RhoA. Mutations in MEFV, encoding pyrin, cause two distinct autoinflammatory diseases pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND) and familial Mediterranean fever (FMF). Monocytes from PAAND patients, and to a lower extent from FMF patients, display increased responses to these metabolites. This study identifies an unconventional pyrin activation mechanism, indicates that endogenous steroid catabolites can drive autoinflammation, through the pyrin inflammasome, and explains the "steroid fever" described in the late 1950s upon steroid injection in humans | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a B30.2 | |
| 650 | 4 | |a CP: Immunology | |
| 650 | 4 | |a CP: Molecular biology | |
| 650 | 4 | |a PAAND | |
| 650 | 4 | |a autoinflammatory disease | |
| 650 | 4 | |a catabolite | |
| 650 | 4 | |a familial Mediterranean fever | |
| 650 | 4 | |a inflammasome | |
| 650 | 4 | |a pregnanolone | |
| 650 | 4 | |a progesterone | |
| 650 | 4 | |a pyrin | |
| 650 | 4 | |a steroid | |
| 650 | 7 | |a Inflammasomes |2 NLM | |
| 650 | 7 | |a MEFV protein, human |2 NLM | |
| 650 | 7 | |a Pyrin |2 NLM | |
| 650 | 7 | |a Testosterone |2 NLM | |
| 650 | 7 | |a 3XMK78S47O |2 NLM | |
| 650 | 7 | |a Progesterone |2 NLM | |
| 650 | 7 | |a 4G7DS2Q64Y |2 NLM | |
| 650 | 7 | |a Etiocholanolone |2 NLM | |
| 650 | 7 | |a 97CGB1M48I |2 NLM | |
| 650 | 7 | |a Pregnanolone |2 NLM | |
| 650 | 7 | |a BXO86P3XXW |2 NLM | |
| 700 | 1 | |a Chirita, Daria |e verfasserin |4 aut | |
| 700 | 1 | |a Dalmon, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Amandine |e verfasserin |4 aut | |
| 700 | 1 | |a Bronnec, Pauline |e verfasserin |4 aut | |
| 700 | 1 | |a Sousa, Jeremy |e verfasserin |4 aut | |
| 700 | 1 | |a Helynck, Olivier |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Wonyong |e verfasserin |4 aut | |
| 700 | 1 | |a Kastner, Daniel L |e verfasserin |4 aut | |
| 700 | 1 | |a Chae, Jae Jin |e verfasserin |4 aut | |
| 700 | 1 | |a McDermott, Michael F |e verfasserin |4 aut | |
| 700 | 1 | |a Belot, Alexandre |e verfasserin |4 aut | |
| 700 | 1 | |a Popoff, Michel |e verfasserin |4 aut | |
| 700 | 1 | |a Sève, Pascal |e verfasserin |4 aut | |
| 700 | 1 | |a Georgin-Lavialle, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Munier-Lehmann, Hélène |e verfasserin |4 aut | |
| 700 | 1 | |a Tran, Tu Anh |e verfasserin |4 aut | |
| 700 | 1 | |a De Langhe, Ellen |e verfasserin |4 aut | |
| 700 | 1 | |a Wouters, Carine |e verfasserin |4 aut | |
| 700 | 1 | |a Jamilloux, Yvan |e verfasserin |4 aut | |
| 700 | 1 | |a Henry, Thomas |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell reports |d 2012 |g 41(2022), 2 vom: 11. Okt., Seite 111472 |w (DE-627)NLM217067492 |x 2211-1247 |7 nnns |
| 773 | 1 | 8 | |g volume:41 |g year:2022 |g number:2 |g day:11 |g month:10 |g pages:111472 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.celrep.2022.111472 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 41 |j 2022 |e 2 |b 11 |c 10 |h 111472 | ||