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Global Proteomic Analyses of STING‐Positive and ‐Negative Macrophages Reveal STING and Non‐STING Differentially Regulated Cellular and Molecular Pathways
Author(s) -
Aryal Uma K.,
Hedrick Victoria,
Onyedibe Kenneth Ikenna,
Sobreira Tiago Jose Paschoal,
Sooreshjani Moloud Aflaki,
Wang Modi,
Gürsoy Ulvi Kahraman,
Sintim Herman O.
Publication year - 2020
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201900109
Subject(s) - sting , biology , microbiology and biotechnology , innate immune system , signal transduction , proteome , immune system , biochemistry , immunology , engineering , aerospace engineering
Purpose Cyclic guanosine monophosphate‐adenosine monophosphate and other bacterial‐derived cyclic di‐guanosine monophosphate or cyclic di‐adenosine monophosphate trigger innate immune responses through binding to stimulator of interferon genes (STING). Thus in chronic infection, such as in periodontitis, immune cells can be exposed to bacterial DNA and/or cyclic dinucleotides, potentially activating STING to cause inflammation. Thus far the cyclic GMP‐AMP synthase‐STING‐ TANK‐binding kinase 1 pathway has been well characterized but a global perspective of how the presence or lack of STING affect the proteome is lacking. The aim of this study is to identify macrophage proteins that are affected by STING. Experimental Design Proteins are extracted from a macrophage cell line harboring STING (RAW‐Blue ISG) as well as a STING knockout (STING KO) cell line (RAW‐Lucia ISG‐KO‐STING) and global proteomics analyses are performed. Results Proteins related to kinase and phosphatase signaling, spliceosome, terpenoid backbone biosynthesis, glycosylation, ubiquitination, and phagocytosis are affected by STING knock out. Conclusions and Clinical Relevance STING pathway in macrophages is related to the regulation of several proteins that are known as potent biomarkers of various cancers and autoimmune diseases. Moreover, the relation between STING and phagocytosis is demonstrated for the first time. Further validation studies will help identify molecules and pathways that may function as diagnostic or therapeutic targets.