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RNA (New York, N.Y.) Jul 2022The poly(A) tail enhances translation and transcript stability, and tail length is under dynamic control during cell state transitions. Tail regulation plays essential...
The poly(A) tail enhances translation and transcript stability, and tail length is under dynamic control during cell state transitions. Tail regulation plays essential roles in translational timing and fertilization in early development, but poly(A) tail dynamics have not been fully explored in post-embryonic systems. Here, we examined the landscape and impact of tail length control during macrophage activation. Upon activation, more than 1500 mRNAs, including proinflammatory genes, underwent distinctive changes in tail lengths. Increases in tail length correlated with mRNA levels regardless of transcriptional activity, and many mRNAs that underwent tail extension encode proteins necessary for immune function and post-transcriptional regulation. Strikingly, we found that , whose protein product destabilizes target transcripts, undergoes tail extension. Our analyses indicate that many mRNAs undergoing tail lengthening are, in turn, degraded by elevated levels of ZFP36, constituting a post-transcriptional feedback loop that ensures transient regulation of transcripts integral to macrophage activation. Taken together, this study establishes the complexity, relevance, and widespread nature of poly(A) tail dynamics, and the resulting post-transcriptional regulation during macrophage activation.
Topics: Gene Expression Regulation; Macrophage Activation; Poly A; Polyadenylation; RNA, Messenger
PubMed: 35512831
DOI: 10.1261/rna.078918.121 -
Antioxidants & Redox Signaling Nov 2016With the growing population of baby boomers, there is a great need to determine the effects of advanced age on the function of the immune system. Recent Advances: It is... (Review)
Review
SIGNIFICANCE
With the growing population of baby boomers, there is a great need to determine the effects of advanced age on the function of the immune system. Recent Advances: It is universally accepted that advanced age is associated with a chronic low-grade inflammatory state that is referred to as inflamm-aging, which alters the function of both immune and nonimmune cells. Mononuclear phagocytes play a central role in both the initiation and resolution of inflammation in multiple organ systems and exhibit marked changes in phenotype and function in response to environmental cues, including the low levels of pro-inflammatory mediators seen in the aged.
CRITICAL ISSUES
Although we know a great deal about the function of immune cells in young adults and there is a growing body of literature focusing on aging of the adaptive immune system, much less is known about the impact of age on innate immunity and the critical role of the mononuclear phagocytes in this process.
FUTURE DIRECTIONS
In this article, there is a focus on the tissue-specific monocyte and macrophage subsets and how they are altered in the aged milieu, with the hope that this compilation of observations will spark an expansion of research in the field. Antioxid. Redox Signal. 25, 805-815.
Topics: Adaptive Immunity; Aging; Animals; Humans; Immunity, Innate; Inflammation; Macrophage Activation; Macrophages; Monocytes; Phenotype; Signal Transduction
PubMed: 27357201
DOI: 10.1089/ars.2016.6691 -
Microbiology Spectrum Oct 2016The functional and phenotypic diversity of macrophages has long been appreciated, and it is now clear that it reflects a complex interplay between hard-wired... (Review)
Review
The functional and phenotypic diversity of macrophages has long been appreciated, and it is now clear that it reflects a complex interplay between hard-wired differentiation pathways and instructive signals in specific tissues (Lawrence T, Natoli G. 2011, Nat Rev Immunol11:750-761). Recent studies have begun to unravel the molecular basis for the integration of these intrinsic developmental pathways with extracellular signals from the tissue microenvironment that confer the distinct phenotypes of tissue-resident macrophages (Lavin Y et al. 2014. Cell159:1312-1326; Gosselin D et al. 2014. Cell159:1327-1340). Macrophage phenotype and function is particularly dynamic during inflammation or infection, as blood monocytes are recruited into tissues and differentiate into macrophages, and depending on the nature of the inflammatory stimulus, they may acquire distinct functional phenotypes (Xue J et al. 2014. Immunity40:274-288; Murray PJ et al. 2014. Immunity41:14-20). Furthermore, these functional activation states can be rapidly modified in response to a changing microenvironment. Here we will discuss several key signaling pathways that drive macrophage activation during the inflammatory response and discuss how these pathways are integrated to "fine-tune" macrophage phenotype and function.
Topics: Animals; Humans; Macrophage Activation; Macrophages; Signal Transduction
PubMed: 27780013
DOI: 10.1128/microbiolspec.MCHD-0025-2015 -
Molecules (Basel, Switzerland) Mar 2022The discovery of safe and effective plant polysaccharides with immunomodulatory effects has become a research hotspot. Raspberry is an essential commercial fruit and is...
The discovery of safe and effective plant polysaccharides with immunomodulatory effects has become a research hotspot. Raspberry is an essential commercial fruit and is widely distributed, cultivated, and consumed worldwide. In the present study, a homogeneous acidic polysaccharide (RPP-2a), with a weight-average molecular weight (Mw) of 55582 Da, was isolated from the pulp of raspberries through DEAE-Sepharose Fast Flow and Sephadex G-200 chromatography. RPP-2a consisted of rhamnose, arabinose, galactose, glucose, xylose, galacturonic acid and glucuronic acid, with a molar ratio of 15.4:9.6:7.6:3.2:9.1:54.3:0.8. The results of Fourier transform infrared spectroscopy (FT-IR), gas chromatography-mass spectrometer (GC-MS), 1D-, and 2D-nuclear magnetic resonance (NMR) analyses suggested that the backbone of RPP-2a was primarily composed of →2)--L-Rha-(1→, →2,4)--L-Rha-(1→, →4)--D-GalA-(1→, and →3,4)--D-Glc-(1→ sugar moieties, with side chains of -L-Ara-(1→, -L-Ara-(1→, and -D-Gal-(1→3)--D-Gal-(1→ residues linked to the O-4 band of rhamnose and O-3 band of glucose residues. Furthermore, RPP-2a exhibited significant macrophage activation activity by increasing the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and the expression of inducible nitric oxide synthase (iNOS) and cytokines at the transcriptional level in RAW264.7 cells. Overall, the results indicate that RPP-2a can be utilized as a potential natural immune-enhancing agent.
Topics: Animals; Macrophage Activation; Mice; Polysaccharides; RAW 264.7 Cells; Rubus; Spectroscopy, Fourier Transform Infrared
PubMed: 35268775
DOI: 10.3390/molecules27051674 -
Immunobiology Oct 2017The alarming rise of obesity and type 2 diabetes (T2D) has put a tremendous strain on global healthcare systems. Over the past decade extensive research has focused on... (Review)
Review
The alarming rise of obesity and type 2 diabetes (T2D) has put a tremendous strain on global healthcare systems. Over the past decade extensive research has focused on the role of macrophages as key mediators of inflammation in T2D. The inflammatory environment in the obese adipose tissue and pancreatic β-cell islets creates and perpetuates imbalanced inflammatory macrophage activation. Consequences of this chronic low-grade inflammation include insulin resistance in the adipose tissue and pancreatic β-cell dysfunction. Recently, the emerging field of epigenetics has provided new insights into the pathogenesis of T2D, while also affording potential new opportunities for treatment. In macrophages, epigenetic mechanisms are increasingly being recognized as crucial controllers of their phenotype. Here, we first describe the role of macrophages in T2D. Then we elaborate on epigenetic mechanisms that regulate macrophage activation, thereby focusing on T2D. Next, we highlight how diabetic conditions such as hyperlipidemia and hyperglycemia could induce epigenetic changes that promote an inflammatory macrophage phenotype. In conclusion we discuss possible therapeutic interventions by targeting macrophage epigenetics and speculate on future research directions.
Topics: Animals; Diabetes Mellitus, Type 2; Epigenesis, Genetic; Humans; Hyperglycemia; Hyperlipidemias; Inflammation; Macrophage Activation; Macrophages; Molecular Targeted Therapy
PubMed: 27613200
DOI: 10.1016/j.imbio.2016.08.011 -
Current Rheumatology Reports May 2019Macrophages play key roles in tissue homeostasis and immune surveillance, mobilizing immune activation in response to microbial invasion and promoting wound healing to... (Review)
Review
PURPOSE OF REVIEW
Macrophages play key roles in tissue homeostasis and immune surveillance, mobilizing immune activation in response to microbial invasion and promoting wound healing to repair damaged tissue. However, failure to resolve macrophage activation can lead to chronic inflammation and fibrosis, and ultimately to pathology. Activated macrophages have been implicated in the pathogenesis of systemic sclerosis (SSc), although the triggers that induce immune activation in SSc and the signaling pathways that underlie aberrant macrophage activation remain unknown.
RECENT FINDINGS
Macrophages are implicated in fibrotic activation in SSc. Targeted therapeutic interventions directed against SSc macrophages may ameliorate inflammation and fibrosis. While current studies have begun to elucidate the role of macrophages in disease initiation and progression, further work is needed to address macrophage subset heterogeneity within and among SSc end-target tissues to determine the disparate functions mediated by these subsets and to identify additional targets for therapeutic intervention.
Topics: Humans; Immunity, Innate; Inflammation; Macrophage Activation; Macrophages; Scleroderma, Systemic
PubMed: 31123840
DOI: 10.1007/s11926-019-0831-z -
Immunity Dec 2019In a recent issue of Nature, Zhang et al. (2019) describe an additional histone post-translational modification, named histone lactylation. Following increased lactate...
In a recent issue of Nature, Zhang et al. (2019) describe an additional histone post-translational modification, named histone lactylation. Following increased lactate production as a consequence of M1 polarization, histone lactylation regulates the induction of an M2-like phenotype in late stages of M1 macrophage activation to promote wound healing.
Topics: Gene Expression Regulation; Histones; Macrophage Activation; Macrophages; Sugars
PubMed: 31851904
DOI: 10.1016/j.immuni.2019.11.008 -
Journal of Interferon & Cytokine... Jul 2016Toll-like receptors (TLRs) are major receptors of the host innate immune system that recognize conserved pathogen-associated molecular patterns (PAMPs) of invading... (Review)
Review
Toll-like receptors (TLRs) are major receptors of the host innate immune system that recognize conserved pathogen-associated molecular patterns (PAMPs) of invading microbes. Activation of TLR signaling culminates in the expression of multiple genes in a coordinate and kinetically defined manner. In this review, we summarize the current studies describing the chromatin landscape of TLR-responsive inflammatory genes and how changes to this chromatin landscape govern cell type-specific and temporal gene expression. We further elaborate classical endotoxin tolerance and epigenetic mechanisms controlling tolerance and interferon priming effects on inflammatory promoters.
Topics: Animals; Chromatin Assembly and Disassembly; Epigenesis, Genetic; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Immune Tolerance; Immunity, Innate; Inflammation; Inflammation Mediators; Interferons; Jumonji Domain-Containing Histone Demethylases; Macrophage Activation; Macrophages; Promoter Regions, Genetic; Toll-Like Receptors
PubMed: 27379867
DOI: 10.1089/jir.2016.0003 -
Journal of Immunology Research 2015The benefits of garlic to health have been proclaimed for centuries; however, only recently have Allium sativum and its derivatives been proposed as promising candidates... (Review)
Review
The benefits of garlic to health have been proclaimed for centuries; however, only recently have Allium sativum and its derivatives been proposed as promising candidates for maintaining the homeostasis of the immune system. The complex biochemistry of garlic makes it possible for variations in processing to yield different preparations with differences in final composition and compound proportion. In this review, we assess the most recent experimental results, which indicate that garlic appears to enhance the functioning of the immune system by stimulating certain cell types, such as macrophages, lymphocytes, natural killer (NK) cells, dendritic cells, and eosinophils, by mechanisms including modulation of cytokine secretion, immunoglobulin production, phagocytosis, and macrophage activation. Finally, because immune dysfunction plays an important role in the development and progress of several diseases, we critically examined immunoregulation by garlic extracts and compounds isolated, which can contribute to the treatment and prevention of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer. We concluded that A. sativum modulates cytokine secretion and that such modulation may provide a mechanism of action for many of their therapeutic effects.
Topics: Cytokines; Dendritic Cells; Eosinophils; Garlic; Humans; Immunomodulation; Inflammation; Killer Cells, Natural; Macrophage Activation; Macrophages; Phagocytosis; Plant Extracts
PubMed: 25961060
DOI: 10.1155/2015/401630 -
Frontiers in Immunology 2022Macrophages are versatile immune cells associated with various diseases, and their phenotypes and functions change on the basis of the surrounding environments.... (Review)
Review
Macrophages are versatile immune cells associated with various diseases, and their phenotypes and functions change on the basis of the surrounding environments. Reprogramming of metabolism is required for the proper polarization of macrophages. This review will focus on basic metabolic pathways, the effects of key enzymes and specific products, relationships between cellular metabolism and macrophage polarization in different diseases and the potential prospect of therapy targeted key metabolic enzymes. In particular, the types and characteristics of macrophages at the maternal-fetal interface and their effects on a successful conception will be discussed.
Topics: Macrophage Activation; Macrophages; Phenotype
PubMed: 35911719
DOI: 10.3389/fimmu.2022.880286