Sphingosine-1-phosphate induces airway smooth muscle hyperresponsiveness and proliferation
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
BACKGROUND: The emerging role of sphingosine-1-phosphate (S1P) in regulating smooth muscle functions has led to the exploration of the possibility that this sphingolipid could represent a potential therapeutic target in asthma and other lung diseases. Several studies in animal surrogates have suggested a role for S1P-mediated signaling in the regulation of airway smooth muscle (ASM) contraction, airway hyperresponsiveness, and airway remodeling, but evidence from human studies is lacking.
OBJECTIVE: We sought to compare the responsiveness of the airways to S1P in healthy and asthmatic individuals in vivo, in isolated human airways ex vivo, and in murine airways dissected from healthy and house dust mite (HDM)-sensitized animals.
METHODS: Airway responsiveness was measured by spirometry during inhalation challenges and by wire myography in airways isolated from human and mouse lungs. Thymidine incorporation and calcium mobilization assays were used to study human ASM cell responses.
RESULTS: S1P did not induce contraction of airways isolated from healthy and HDM-exposed mice, nor in human airways. Similarly, there was no airway constriction observed in healthy and asthmatic subjects in response to increasing concentrations of inhaled S1P. However, a 30-minute exposure to S1P induced a significant concentration-dependent enhancement of airway reactivity to methacholine and to histamine in murine and human airways, respectively. HDM-sensitized mice demonstrated a significant increase in methacholine responsiveness, which was not further enhanced by S1P treatment. S1P also concentration-dependently enhanced proliferation of human ASM cells, an effect mediated through S1P receptor type 2, as shown by selective antagonism and S1P receptor type 2 small-interfering RNA knockdown.
CONCLUSIONS: Our data suggest that S1P released locally into the airways may be involved in the regulation of ASM hyperresponsiveness and hyperplasia, defining a novel target for future therapies.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:152 |
|---|---|
| Enthalten in: |
The Journal of allergy and clinical immunology - 152(2023), 5 vom: 24. Nov., Seite 1131-1140.e6 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Maguire, Thomas J A [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
0W5ETF9M2K |
|---|
| Anmerkungen: |
Date Completed 07.11.2023 Date Revised 13.11.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jaci.2023.05.028 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM359744605 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM359744605 | ||
| 003 | DE-627 | ||
| 005 | 20231226081530.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jaci.2023.05.028 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1199.xml |
| 035 | |a (DE-627)NLM359744605 | ||
| 035 | |a (NLM)37474025 | ||
| 035 | |a (PII)S0091-6749(23)00891-6 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Maguire, Thomas J A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Sphingosine-1-phosphate induces airway smooth muscle hyperresponsiveness and proliferation |
| 264 | 1 | |c 2023 | |
| 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 07.11.2023 | ||
| 500 | |a Date Revised 13.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: The emerging role of sphingosine-1-phosphate (S1P) in regulating smooth muscle functions has led to the exploration of the possibility that this sphingolipid could represent a potential therapeutic target in asthma and other lung diseases. Several studies in animal surrogates have suggested a role for S1P-mediated signaling in the regulation of airway smooth muscle (ASM) contraction, airway hyperresponsiveness, and airway remodeling, but evidence from human studies is lacking | ||
| 520 | |a OBJECTIVE: We sought to compare the responsiveness of the airways to S1P in healthy and asthmatic individuals in vivo, in isolated human airways ex vivo, and in murine airways dissected from healthy and house dust mite (HDM)-sensitized animals | ||
| 520 | |a METHODS: Airway responsiveness was measured by spirometry during inhalation challenges and by wire myography in airways isolated from human and mouse lungs. Thymidine incorporation and calcium mobilization assays were used to study human ASM cell responses | ||
| 520 | |a RESULTS: S1P did not induce contraction of airways isolated from healthy and HDM-exposed mice, nor in human airways. Similarly, there was no airway constriction observed in healthy and asthmatic subjects in response to increasing concentrations of inhaled S1P. However, a 30-minute exposure to S1P induced a significant concentration-dependent enhancement of airway reactivity to methacholine and to histamine in murine and human airways, respectively. HDM-sensitized mice demonstrated a significant increase in methacholine responsiveness, which was not further enhanced by S1P treatment. S1P also concentration-dependently enhanced proliferation of human ASM cells, an effect mediated through S1P receptor type 2, as shown by selective antagonism and S1P receptor type 2 small-interfering RNA knockdown | ||
| 520 | |a CONCLUSIONS: Our data suggest that S1P released locally into the airways may be involved in the regulation of ASM hyperresponsiveness and hyperplasia, defining a novel target for future therapies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Asthma | |
| 650 | 4 | |a airway contraction | |
| 650 | 4 | |a airway smooth muscle | |
| 650 | 4 | |a sphingolipids | |
| 650 | 7 | |a Sphingosine-1-Phosphate Receptors |2 NLM | |
| 650 | 7 | |a sphingosine 1-phosphate |2 NLM | |
| 650 | 7 | |a 26993-30-6 |2 NLM | |
| 650 | 7 | |a Methacholine Chloride |2 NLM | |
| 650 | 7 | |a 0W5ETF9M2K |2 NLM | |
| 700 | 1 | |a Yung, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Ortiz-Zapater, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Kayode, O Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Till, Stephen |e verfasserin |4 aut | |
| 700 | 1 | |a Corrigan, Chris |e verfasserin |4 aut | |
| 700 | 1 | |a Siew, Leonard Q C |e verfasserin |4 aut | |
| 700 | 1 | |a Knock, Gregory A |e verfasserin |4 aut | |
| 700 | 1 | |a Woszczek, Grzegorz |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of allergy and clinical immunology |d 1971 |g 152(2023), 5 vom: 24. Nov., Seite 1131-1140.e6 |w (DE-627)NLM000018449 |x 1097-6825 |7 nnns |
| 773 | 1 | 8 | |g volume:152 |g year:2023 |g number:5 |g day:24 |g month:11 |g pages:1131-1140.e6 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jaci.2023.05.028 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 152 |j 2023 |e 5 |b 24 |c 11 |h 1131-1140.e6 | ||