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Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein

Respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and lung infections have critical consequences on mortality and morbidity in humans. The aims of the present study were to examine the mechanisms by which CXCL12 affects MUC1 transcription and airway inflammation, whi...

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Autores principales: Choi, IL-Whan, Ahn, Do Whan, Choi, Jang-Kyu, Cha, Hee-Jae, Ock, Mee Sun, You, EunAe, Rhee, SangMyung, Kim, Kwang Chul, Choi, Yung Hyun, Song, Kyoung Seob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895231/
https://www.ncbi.nlm.nih.gov/pubmed/27270970
http://dx.doi.org/10.1038/srep27054
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author Choi, IL-Whan
Ahn, Do Whan
Choi, Jang-Kyu
Cha, Hee-Jae
Ock, Mee Sun
You, EunAe
Rhee, SangMyung
Kim, Kwang Chul
Choi, Yung Hyun
Song, Kyoung Seob
author_facet Choi, IL-Whan
Ahn, Do Whan
Choi, Jang-Kyu
Cha, Hee-Jae
Ock, Mee Sun
You, EunAe
Rhee, SangMyung
Kim, Kwang Chul
Choi, Yung Hyun
Song, Kyoung Seob
author_sort Choi, IL-Whan
collection PubMed
description Respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and lung infections have critical consequences on mortality and morbidity in humans. The aims of the present study were to examine the mechanisms by which CXCL12 affects MUC1 transcription and airway inflammation, which depend on activator of G-protein signaling (AGS) 3 and to identify specific molecules that suppress CXCL12-induced airway inflammation by acting on G-protein-coupled receptors. Herein, AGS3 suppresses CXCL12-mediated upregulation of MUC1 and TNFα by regulating Gα(i). We found that the G-protein regulatory (GPR) motif peptide in AGS3 binds to Gα(i) and downregulates MUC1 expression; in contrast, this motif upregulates TNFα expression. Mutated GPR Q34A peptide increased the expression of MUC1 and TGFβ but decreased the expression of TNFα and IL-6. Moreover, CXCR4-induced dendritic extensions in 2D and 3D matrix cultures were inhibited by the GPR Q34A peptide compared with a wild-type GPR peptide. The GPR Q34A peptide also inhibited CXCL12-induced morphological changes and inflammatory cell infiltration in the mouse lung, and production of inflammatory cytokines in bronchoalveolar lavage (BAL) fluid and the lungs. Our data indicate that the GPR motif of AGS3 is critical for regulating MUC1/Muc1 expression and cytokine production in the inflammatory microenvironment.
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spelling pubmed-48952312016-06-10 Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein Choi, IL-Whan Ahn, Do Whan Choi, Jang-Kyu Cha, Hee-Jae Ock, Mee Sun You, EunAe Rhee, SangMyung Kim, Kwang Chul Choi, Yung Hyun Song, Kyoung Seob Sci Rep Article Respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and lung infections have critical consequences on mortality and morbidity in humans. The aims of the present study were to examine the mechanisms by which CXCL12 affects MUC1 transcription and airway inflammation, which depend on activator of G-protein signaling (AGS) 3 and to identify specific molecules that suppress CXCL12-induced airway inflammation by acting on G-protein-coupled receptors. Herein, AGS3 suppresses CXCL12-mediated upregulation of MUC1 and TNFα by regulating Gα(i). We found that the G-protein regulatory (GPR) motif peptide in AGS3 binds to Gα(i) and downregulates MUC1 expression; in contrast, this motif upregulates TNFα expression. Mutated GPR Q34A peptide increased the expression of MUC1 and TGFβ but decreased the expression of TNFα and IL-6. Moreover, CXCR4-induced dendritic extensions in 2D and 3D matrix cultures were inhibited by the GPR Q34A peptide compared with a wild-type GPR peptide. The GPR Q34A peptide also inhibited CXCL12-induced morphological changes and inflammatory cell infiltration in the mouse lung, and production of inflammatory cytokines in bronchoalveolar lavage (BAL) fluid and the lungs. Our data indicate that the GPR motif of AGS3 is critical for regulating MUC1/Muc1 expression and cytokine production in the inflammatory microenvironment. Nature Publishing Group 2016-06-07 /pmc/articles/PMC4895231/ /pubmed/27270970 http://dx.doi.org/10.1038/srep27054 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Choi, IL-Whan
Ahn, Do Whan
Choi, Jang-Kyu
Cha, Hee-Jae
Ock, Mee Sun
You, EunAe
Rhee, SangMyung
Kim, Kwang Chul
Choi, Yung Hyun
Song, Kyoung Seob
Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein
title Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein
title_full Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein
title_fullStr Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein
title_full_unstemmed Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein
title_short Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein
title_sort regulation of airway inflammation by g-protein regulatory motif peptides of ags3 protein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895231/
https://www.ncbi.nlm.nih.gov/pubmed/27270970
http://dx.doi.org/10.1038/srep27054
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