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

Persistent Link:
http://hdl.handle.net/10150/617184
Title:
Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein
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
Affiliation:
Univ Arizona, Dept Otolaryngol Head & Neck Surg, Coll Med
Issue Date:
2016-06-07
Publisher:
NATURE PUBLISHING GROUP
Citation:
Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein 2016, 6:27054 Scientific Reports
Journal:
Scientific Reports
Rights:
This work is licensed under a Creative Commons Attribution 4.0 International License.
Collection Information:
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
Abstract:
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 TNF alpha by regulating G(alpha i). We found that the G-protein regulatory (GPR) motif peptide in AGS3 binds to G(alpha i) and downregulates MUC1 expression; in contrast, this motif upregulates TNF alpha expression. Mutated GPR Q34A peptide increased the expression of MUC1 and TGF beta but decreased the expression of TNF alpha 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.
Note:
Open access.
ISSN:
2045-2322
DOI:
10.1038/srep27054
Version:
Final published version
Sponsors:
Basic Science Research Program through the National Research Foundation of Korea (NRF) grant - Korea government [2015R1A2A2A01004633]; National Research Foundation of Korea, - Korean government (MEST) [2014-R1A1A2055774]
Additional Links:
http://www.nature.com/articles/srep27054

Full metadata record

DC FieldValue Language
dc.contributor.authorChoi, IL-Whanen
dc.contributor.authorAhn, Do Whanen
dc.contributor.authorChoi, Jang-Kyuen
dc.contributor.authorCha, Hee-Jaeen
dc.contributor.authorOck, Mee Sunen
dc.contributor.authorYou, EunAeen
dc.contributor.authorRhee, SangMyungen
dc.contributor.authorKim, Kwang Chulen
dc.contributor.authorChoi, Yung Hyunen
dc.contributor.authorSong, Kyoung Seoben
dc.date.accessioned2016-07-19T02:07:19Z-
dc.date.available2016-07-19T02:07:19Z-
dc.date.issued2016-06-07-
dc.identifier.citationRegulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein 2016, 6:27054 Scientific Reportsen
dc.identifier.issn2045-2322-
dc.identifier.doi10.1038/srep27054-
dc.identifier.urihttp://hdl.handle.net/10150/617184-
dc.description.abstractRespiratory 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 TNF alpha by regulating G(alpha i). We found that the G-protein regulatory (GPR) motif peptide in AGS3 binds to G(alpha i) and downregulates MUC1 expression; in contrast, this motif upregulates TNF alpha expression. Mutated GPR Q34A peptide increased the expression of MUC1 and TGF beta but decreased the expression of TNF alpha 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.en
dc.description.sponsorshipBasic Science Research Program through the National Research Foundation of Korea (NRF) grant - Korea government [2015R1A2A2A01004633]; National Research Foundation of Korea, - Korean government (MEST) [2014-R1A1A2055774]en
dc.language.isoenen
dc.publisherNATURE PUBLISHING GROUPen
dc.relation.urlhttp://www.nature.com/articles/srep27054en
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License.en
dc.titleRegulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 proteinen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Dept Otolaryngol Head & Neck Surg, Coll Meden
dc.identifier.journalScientific Reportsen
dc.description.noteOpen access.en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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