Inflammation and tumor progression: signaling pathways and targeted intervention

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: July 12, 2021

Abstract Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses tumor progression, potentially displaying opposing effects on therapeutic outcomes. Chronic inflammation facilitates progression treatment resistance, whereas induction of acute inflammatory reactions often stimulates the maturation dendritic cells (DCs) antigen presentation, leading anti-tumor immune responses. In addition, multiple signaling pathways, such as nuclear factor kappa B (NF-kB), Janus kinase/signal transducers activators transcription (JAK-STAT), toll-like receptor (TLR) cGAS/STING, mitogen-activated protein kinase (MAPK); factors, including cytokines (e.g., interleukin (IL), interferon (IFN), necrosis (TNF)-α), chemokines C-C motif chemokine ligands (CCLs) C-X-C (CXCLs)), growth factors vascular endothelial (VEGF), transforming (TGF)-β), inflammasome; well metabolites prostaglandins, leukotrienes, thromboxane, specialized proresolving mediators (SPM), have been identified pivotal regulators initiation resolution inflammation. Nowadays, local irradiation, recombinant cytokines, neutralizing antibodies, small-molecule inhibitors, DC vaccines, oncolytic viruses, TLR agonists, SPM developed specifically modulate in cancer therapy, with some these already undergoing clinical trials. Herein, we discuss crosstalk between processes. We also highlight potential targets for harnessing cancer.

Language: Английский

---

The Metabolic Signature of Macrophage Responses

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: July 3, 2019

Macrophages are a heterogeneous population of immune cells playing several and diverse functions in homeostatic responses. The broad spectrum macrophage depends on both heterogeneity plasticity these cells, which highly specialized sensing the microenvironment modify their properties accordingly. Although it is clear that phenotypes difficult to categorize should be seen as plastic adaptable, they can simplified into two extremes: pro-inflammatory (M1) an anti-inflammatory/pro-resolving (M2) profile. Based this definition, M1 macrophages able start sustain inflammatory responses, secreting cytokines, activating endothelial inducing recruitment other inflamed tissue; hand, M2 promote resolution inflammation, phagocytose apoptotic drive collagen deposition, coordinate tissue integrity, release anti-inflammatory mediators. Dramatic switches cell metabolism accompany phenotypic functional changes macrophages. In particular, rely mainly glycolysis present breaks TCA cycle result accumulation itaconate (a microbicide compound) succinate. Excess succinate leads Hypoxia Inducible Factor 1 (HIF1) stabilization that, turn, activates transcription glycolytic genes, thus sustaining On contrary, more dependent oxidative phosphorylation (OXPHOS), intact provides substrates for complexes electron transport chain (ETC). Moreover, pro- characterized by specific pathways regulate lipids amino acids affect All metabolic adaptations support activities well polarization contexts. aim review discuss recent findings linking metabolism.

Language: Английский

---

The Gut Microbiome, Kidney Disease, and Targeted Interventions

Journal of the American Society of Nephrology, Journal Year: 2013, Volume and Issue: 25(4), P. 657 - 670

Published: Nov. 15, 2013

The human gut harbors >100 trillion microbial cells, which influence the nutrition, metabolism, physiology, and immune function of host. Here, we review quantitative qualitative changes in microbiota patients with CKD that lead to disturbance this symbiotic relationship, how may contribute progression CKD, targeted interventions re-establish symbiosis. Endotoxin derived from bacteria incites a powerful inflammatory response host organism. Furthermore, protein fermentation by generates myriad toxic metabolites, including p-cresol indoxyl sulfate. Disruption barrier allows translocation endotoxin bacterial metabolites systemic circulation, contributes uremic toxicity, inflammation, associated cardiovascular disease. Several aim intestinal symbiosis, neutralize endotoxins, or adsorb gut-derived toxins have been developed. Indeed, animal studies suggest prebiotics probiotics therapeutic roles maintaining metabolically-balanced reducing uremia-associated complications. We propose further research should focus on using highly efficient metabolic machinery alleviate symptoms.

Language: Английский

---

Macrophages and the Recovery from Acute and Chronic Inflammation

Annual Review of Physiology, Journal Year: 2016, Volume and Issue: 79(1), P. 567 - 592

Published: Dec. 13, 2016

In recent years, researchers have devoted much attention to the diverse roles of macrophages and their contributions tissue development, wound healing, angiogenesis. What should not be lost in discussions regarding biology these cells is that when perturbed, are primary contributors potentially pathological inflammatory processes. Macrophages stand poised rapidly produce large amounts cytokines response danger signals. The production can initiate a cascade mediator release lead wholesale destruction. destructive capability amplified by exposure exogenous interferon-γ, which prolongs heightens responses. simple terms, thus viewed as incendiary devices with hair triggers waiting detonate. We begun ask questions about how regulated mitigate collateral destruction associated macrophage activation.

Language: Английский

---

Transcriptional Control of Macrophage Polarization

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2013, Volume and Issue: 33(6), P. 1135 - 1144

Published: May 3, 2013

Macrophages are key regulators of many organ systems, including innate and adaptive immunity, systemic metabolism, hematopoiesis, vasculogenesis, malignancy, reproduction. The pleiotropic roles macrophages mirrored by similarly diverse cellular phenotypes. A simplified schema classifies as M1, classically activated macrophages, or M2, alternatively macrophages. These cells characterized their expression cell surface markers, secreted cytokines chemokines, transcription epigenetic pathways. Transcriptional regulation is central to the differential speciation several major pathways have been described essential for subset differentiation. In this review, we discuss transcriptional

Language: Английский

---

Neural circuitry engaged by prostaglandins during the sickness syndrome

Nature Neuroscience, Journal Year: 2012, Volume and Issue: 15(8), P. 1088 - 1095

Published: July 26, 2012

Language: Английский

---

TSC1 controls macrophage polarization to prevent inflammatory disease

Nature Communications, Journal Year: 2014, Volume and Issue: 5(1)

Published: Sept. 1, 2014

Language: Английский

---

The Role of Mitogen-Activated Protein Kinase-Activated Protein Kinases (MAPKAPKs) in Inflammation

Genes, Journal Year: 2013, Volume and Issue: 4(2), P. 101 - 133

Published: March 26, 2013

Mitogen-activated protein kinase (MAPK) pathways are implicated in several cellular processes including proliferation, differentiation, apoptosis, cell survival, motility, metabolism, stress response and inflammation. MAPK transmit convert a plethora of extracellular signals by three consecutive phosphorylation events involving kinase, MAPK. In turn MAPKs phosphorylate substrates, other kinases referred to as MAPK-activated (MAPKAPKs). Eleven mammalian MAPKAPKs have been identified: ribosomal-S6-kinases (RSK1-4), mitogen- stress-activated (MSK1-2), MAPK-interacting (MNK1-2), MAPKAPK-2 (MK2), MAPKAPK-3 (MK3), MAPKAPK-5 (MK5). The role these inflammation will be reviewed.

Language: Английский

---

Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury

Molecular Medicine Reports, Journal Year: 2018, Volume and Issue: unknown

Published: Aug. 24, 2018

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is characterized by uncontrolled progressive inflammation. Macrophages serve a key role in the pathogenesis of ALI/ARDS. Macrophage pyroptosis process cell death releasing proinflammatory cytokines interleukin (IL)‑1β IL‑18. It was hypothesized that macrophage may partially account for inflammation In present study, greater lipopolysaccharide (LPS)‑treated macrophages ALI/ARDS mouse model observed. The expression nucleotide‑binding domain, leucine‑rich‑containing family, pyrin domain‑containing (NLRP)3 IL‑1β cleavage caspase‑1 were significantly elevated following LPS treatment accompanied activation p38 mitogen‑activated protein kinase (MAPK) signaling vitro vivo. However, blocking MAPK through inhibitor SB203580 suppressed excessive vivo, consistent with reduced NLRP3 inflammasome caspase‑1. Pretreatment rat NR8383 line decreased population caspase‑1+PI+ pyroptotic cells NLRP3/IL‑1β. larger Annexin V+PI‑ apoptotic observed pathway. results indicated blockage pathway skewed from towards non‑inflammatory apoptosis. These effects contribute to attenuated SB203580‑treated mice. provide novel therapeutic strategy patients

Language: Английский

---

Liver regeneration and inflammation: from fundamental science to clinical applications

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(9), P. 608 - 624

Published: June 2, 2021

Language: Английский

---