Transcriptome profiling reveals new insights into the roles of neuronal nitric oxide synthase on macrophage polarization towards classically activated phenotype

Autor: Quan Sun, Hao Gao, Ping-An Chang, Feifei Huang, Xiaohong He
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Lipopolysaccharides
Male
Physiology
Cellular differentiation
Gene Expression
Nitric Oxide Synthase Type I
Biochemistry
Transcriptome
Gene Knockout Techniques
Mice
White Blood Cells
Cell Signaling
Animal Cells
Immune Physiology
Medicine and Health Sciences
Membrane Receptor Signaling
Immune Response
Cells
Cultured
Innate Immune System
Multidisciplinary
Chemistry
Transcriptional Control
Cell Polarity
M2 Macrophage
Immune Receptor Signaling
Cell biology
Knockout mouse
Medicine
Cytokines
Female
Signal transduction
Cellular Types
Research Article
Signal Transduction
NOS1
Science
Immune Cells
Immunology
Macrophage polarization
Signs and Symptoms
DNA-binding proteins
Genetics
Animals
Gene Regulation
Inflammation
Blood Cells
Biology and life sciences
Sequence Analysis
RNA
Gene Expression Profiling
Macrophages
Proteins
Cell Biology
Macrophage Activation
Molecular Development
Retraction
Regulatory Proteins
Gene Expression Regulation
Immune System
TLR4
Clinical Medicine
Developmental Biology
Transcription Factors
Zdroj: PLoS ONE
PLoS ONE, Vol 16, Iss 9, p e0257908 (2021)
ISSN: 1932-6203
Popis: In response to various stimuli, naïve macrophages usually polarize to M1 (classically activated) or M2 (alternatively activated) cells with distinct biological functions. Neuronal nitric oxide synthase (NOS1) is involved in M1 macrophage polarization at an early stage. Here, we show for the first time that NOS1 is dispensable for M2 macrophage polarization for the first time. Further, differentially expressed genes (DEGs) regulated by NOS1 signaling in M1-polarized macrophages stimulated with lipopolysaccharide (LPS) were characterized by transcriptome analysis of wild-type (WT) and NOS1 knockout mouse macrophages. Thousands of affected genes were detected 2 h post LPS challenge, and this wide-ranging effect became greater with a longer stimulation time (8 h post LPS). NOS1 deficiency caused dysregulated expression of hundreds of LPS-responsive genes. Most DEGs were enriched in biological processes related to transcription and regulation of the immune and inflammatory response. At 2 h post-LPS, the toll-like receptor (TLR) signaling pathway, cytokine–cytokine receptor interaction, and NOD-like receptor signaling pathway were the major pathways affected, whereas the main pathways affected at 8 h post-LPS were Th1 and Th2 cell differentiation, FoxO, and AMPK signaling pathway. Identified DEGs were validated by real-time quantitative PCR and interacted in a complicated signaling pathway network. Collectively, our data show that NOS1 is dispensable for M2 macrophage polarization and reveal novel insights in the role of NOS1 signaling at different stages of M1 macrophage polarization through distinct TLR4 plasma membrane-localized and endosome-internalized signaling pathways.
Databáze: OpenAIRE
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