Open AccessRegulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein
Author(s) -
IlWhan Choi,
Do Whan Ahn,
Jang-Kyu Choi,
HeeJae Cha,
Mee Sun Ock,
Eunae You,
Sangmyung Rhee,
Kwang Chul Kim,
Yung Hyun Choi,
Kyoung Seob Song
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep27054
Subject(s) - inflammation , proinflammatory cytokine , downregulation and upregulation , bronchoalveolar lavage , tumor necrosis factor alpha , peptide , chemokine , microbiology and biotechnology , muc1 , biology , receptor , immunology , chemistry , lung , medicine , immunohistochemistry , biochemistry , gene
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.