Glucagon-like peptide-1 receptor agonist inhibits aeroallergen-induced activation of ILC2 and neutrophilic airway inflammation in obese mice
© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd..
BACKGROUND: Obesity is a risk factor for the development of asthma. However, pharmacologic therapeutic strategies that specifically target obese asthmatics have not been identified. We hypothesize that glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment inhibits aeroallergen-induced early innate airway inflammation in a mouse model of asthma in the setting of obesity.
METHODS: SWR (lean) and TALLYHO (obese) mice were challenged intranasally with Alternaria alternata extract (Alt-Ext) or PBS for 4 consecutive days concurrent with GLP-1RA or vehicle treatment.
RESULTS: TALLYHO mice had greater Alt-Ext-induced airway neutrophilia and lung protein expression of IL-5, IL-13, CCL11, CXCL1, and CXCL5, in addition to ICAM-1 expression on lung epithelial cells compared with SWR mice, and all endpoints were reduced by GLP-1RA treatment. Alt-Ext significantly increased BALF IL-33 in both TALLYHO and SWR mice compared to PBS challenge, but there was no difference in the BALF IL-33 levels between these two strains. However, TALLYHO, but not SWR, mice had significantly higher airway TSLP in BALF following Alt-Ext challenge compared to PBS, and BALF TSLP was significantly greater in TALLYHO mice compared to SWR mice following airway Alt-Ext challenge. GLP-1RA treatment significantly decreased the Alt-Ext-induced TSLP and IL-33 release in TALLYHO mice. While TSLP or ST2 inhibition with a neutralizing antibody decreased airway eosinophils, they did not reduce airway neutrophils in TALLYHO mice.
CONCLUSIONS: These results suggest that GLP-1RA treatment may be a novel pharmacologic therapeutic strategy for obese persons with asthma by inhibiting aeroallergen-induced neutrophilia, a feature not seen with either TSLP or ST2 inhibition.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:76 |
|---|---|
| Enthalten in: |
Allergy - 76(2021), 11 vom: 24. Nov., Seite 3433-3445 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Toki, Shinji [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 15.11.2021 Date Revised 08.12.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/all.14879 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM325071616 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM325071616 | ||
| 003 | DE-627 | ||
| 005 | 20231227130511.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/all.14879 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1224.xml |
| 035 | |a (DE-627)NLM325071616 | ||
| 035 | |a (NLM)33955007 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Toki, Shinji |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Glucagon-like peptide-1 receptor agonist inhibits aeroallergen-induced activation of ILC2 and neutrophilic airway inflammation in obese mice |
| 264 | 1 | |c 2021 | |
| 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 15.11.2021 | ||
| 500 | |a Date Revised 08.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND: Obesity is a risk factor for the development of asthma. However, pharmacologic therapeutic strategies that specifically target obese asthmatics have not been identified. We hypothesize that glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment inhibits aeroallergen-induced early innate airway inflammation in a mouse model of asthma in the setting of obesity | ||
| 520 | |a METHODS: SWR (lean) and TALLYHO (obese) mice were challenged intranasally with Alternaria alternata extract (Alt-Ext) or PBS for 4 consecutive days concurrent with GLP-1RA or vehicle treatment | ||
| 520 | |a RESULTS: TALLYHO mice had greater Alt-Ext-induced airway neutrophilia and lung protein expression of IL-5, IL-13, CCL11, CXCL1, and CXCL5, in addition to ICAM-1 expression on lung epithelial cells compared with SWR mice, and all endpoints were reduced by GLP-1RA treatment. Alt-Ext significantly increased BALF IL-33 in both TALLYHO and SWR mice compared to PBS challenge, but there was no difference in the BALF IL-33 levels between these two strains. However, TALLYHO, but not SWR, mice had significantly higher airway TSLP in BALF following Alt-Ext challenge compared to PBS, and BALF TSLP was significantly greater in TALLYHO mice compared to SWR mice following airway Alt-Ext challenge. GLP-1RA treatment significantly decreased the Alt-Ext-induced TSLP and IL-33 release in TALLYHO mice. While TSLP or ST2 inhibition with a neutralizing antibody decreased airway eosinophils, they did not reduce airway neutrophils in TALLYHO mice | ||
| 520 | |a CONCLUSIONS: These results suggest that GLP-1RA treatment may be a novel pharmacologic therapeutic strategy for obese persons with asthma by inhibiting aeroallergen-induced neutrophilia, a feature not seen with either TSLP or ST2 inhibition | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a glucagon-like peptide-1 receptor (GLP-1R) | |
| 650 | 4 | |a group 2 innate lymphoid cells (ILC2) | |
| 650 | 4 | |a liraglutide | |
| 650 | 4 | |a neutrophilia | |
| 650 | 4 | |a obese asthma | |
| 650 | 7 | |a Glucagon-Like Peptide-1 Receptor |2 NLM | |
| 700 | 1 | |a Newcomb, Dawn C |e verfasserin |4 aut | |
| 700 | 1 | |a Printz, Richard L |e verfasserin |4 aut | |
| 700 | 1 | |a Cahill, Katherine N |e verfasserin |4 aut | |
| 700 | 1 | |a Boyd, Kelli L |e verfasserin |4 aut | |
| 700 | 1 | |a Niswender, Kevin D |e verfasserin |4 aut | |
| 700 | 1 | |a Peebles, R Stokes |c Jr |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Allergy |d 1980 |g 76(2021), 11 vom: 24. Nov., Seite 3433-3445 |w (DE-627)NLM000313874 |x 1398-9995 |7 nnns |
| 773 | 1 | 8 | |g volume:76 |g year:2021 |g number:11 |g day:24 |g month:11 |g pages:3433-3445 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/all.14879 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 76 |j 2021 |e 11 |b 24 |c 11 |h 3433-3445 | ||