Tuning immunity through tissue mechanotransduction

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(3), P. 174 - 188

Published: Aug. 16, 2022

Language: Английский

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Caspase‐11 non‐canonical inflammasome: a critical sensor of intracellular lipopolysaccharide in macrophage‐mediated inflammatory responses

Immunology, Journal Year: 2017, Volume and Issue: 152(2), P. 207 - 217

Published: July 11, 2017

Inflammatory responses mediated by macrophages are part of the innate immune system, whose role is to protect against invading pathogens. Lipopolysaccharide (LPS) found in outer membrane Gram-negative bacteria stimulates an inflammatory response macrophages. During response, extracellular LPS recognized Toll-like receptor 4, one pattern recognition receptors that activates signalling pathways and leads production mediators. The also triggered intracellular inflammasomes, inflammasome activation induces pyroptosis secretion pro-inflammatory cytokines such as interleukin-1β (IL-1β) IL-18 Cysteine-aspartic protease (caspase)-11 human orthologues caspase-4/caspase-5 were recently identified components 'non-canonical inflammasome' senses derived from during macrophage-mediated responses. Direct facilitates rapid oligomerization caspase-11/4/5, which results IL-1β IL-18. released into cytoplasm bacterium-containing vacuoles small interferon-inducible guanylate-binding proteins encoded on chromosome 3 (GBPchr3 )-mediated lysis vacuoles. In vivo studies have clearly shown caspase-11-/- mice more resistant endotoxic septic shock excessive challenge. Given evidence, caspase-11 non-canonical inflammasomes distinct canonical provides a new paradigm

Language: Английский

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Type I collagen decorated nanoporous network on titanium implant surface promotes osseointegration through mediating immunomodulation, angiogenesis, and osteogenesis

Biomaterials, Journal Year: 2022, Volume and Issue: 288, P. 121684 - 121684

Published: July 20, 2022

Language: Английский

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Alzheimer’s Disease: Novel Targets and Investigational Drugs for Disease Modification

Drugs, Journal Year: 2023, Volume and Issue: 83(15), P. 1387 - 1408

Published: Sept. 20, 2023

Novel agents addressing non-amyloid, non-tau targets in Alzheimer's Disease (AD) comprise 70% of the AD drug development pipeline currently clinical trials. Most target processes identified Common Research Ontology (CADRO) are represented by novel Inflammation and synaptic plasticity/neuroprotection CADRO categories with largest number candidate therapies. Within these categories, there few overlapping among test agents. Additional being evaluated include apolipoprotein E $$\varepsilon$$ 4 (APOE4) effects, lipids lipoprotein receptors, neurogenesis, oxidative stress, bioenergetics metabolism, vascular factors, cell death, growth factors hormones, circadian rhythm, epigenetic regulators. We highlight current drugs tested within their mechanisms. Trials will be informative regarding which can modulated to produce a slowing decline. Possible therapeutic combinations may suggested trial outcomes. Biomarkers evolving concert new agents, biomarker outcomes offer means supporting disease modification putative treatment. Identification corresponding therapeutics an important advancing treatments for AD.

Language: Английский

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Macrophages promote anti-androgen resistance in prostate cancer bone disease

The Journal of Experimental Medicine, Journal Year: 2023, Volume and Issue: 220(4)

Published: Feb. 7, 2023

Metastatic castration-resistant prostate cancer (PC) is the final stage of PC that acquires resistance to androgen deprivation therapies (ADT). Despite progresses in understanding disease mechanisms, specific contribution metastatic microenvironment ADT remains largely unknown. The current study identified macrophage major microenvironmental component bone-metastatic patients. Using a novel vivo model, we demonstrated macrophages were critical for enzalutamide through induction wound-healing–like response ECM–receptor gene expression. Mechanistically, drove cytokine activin A induced fibronectin (FN1)-integrin alpha 5 (ITGA5)–tyrosine kinase Src (SRC) signaling cascade cells. This mechanism was strongly supported by bioinformatics analysis patient transcriptomics datasets. Furthermore, depletion or SRC inhibition using inhibitor significantly inhibited resistant growth. Together, our findings elucidated macrophage-induced anti-androgen and promising therapeutic approach treat this deadly disease.

Language: Английский

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Artesunate improves glucose and lipid metabolism in db/db mice by regulating the metabolic profile and the MAPK/PI3K/Akt signalling pathway

Phytomedicine, Journal Year: 2024, Volume and Issue: 126, P. 155382 - 155382

Published: Jan. 30, 2024

Language: Английский

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Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

Mediators of Inflammation, Journal Year: 2014, Volume and Issue: 2014, P. 1 - 12

Published: Jan. 1, 2014

Inflammation is a series of complex biological responses to protect the host from pathogen invasion. Chronic inflammation considered major cause diseases, such as various types inflammatory/autoimmune diseases and cancers. Spleen tyrosine kinase (Syk) was initially found be highly expressed in hematopoietic cells has been known play crucial roles adaptive immune responses. However, recent studies have reported that Syk also involved other functions, especially innate Although extensively studied responses, numerous recently presented evidence critical functions macrophage-mediated inflammatory closely related response. This review describes characteristics Syk-mediated signaling pathways, summarizes findings supporting discusses Syk-targeted drug development for therapy diseases.

Language: Английский

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Andrographolide, an Anti-Inflammatory Multitarget Drug: All Roads Lead to Cellular Metabolism

Molecules, Journal Year: 2020, Volume and Issue: 26(1), P. 5 - 5

Published: Dec. 22, 2020

Andrographolide is a labdane diterpene and the main active ingredient isolated from herb Andrographis paniculata. possesses diverse biological effects including anti-inflammatory, antioxidant, antineoplastic properties. Clinical studies have demonstrated that andrographolide could be useful in therapy for wide range of diseases such as osteoarthritis, upper respiratory diseases, multiple sclerosis. Several targets are described andrographolide, interference transcription factors NF-κB, AP-1, HIF-1 signaling pathways PI3K/Akt, MAPK, JAK/STAT. In addition, an increase Nrf2 (nuclear factor erythroid 2-related 2) pathway also supports its antioxidant anti-inflammatory However, this scenario more complex since recent evidence suggests can modulate glucose metabolism. The metabolic effect might key to explaining therapeutic preclinical clinical studies. This review discusses some most about andrographolide.

Language: Английский

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Redox and Src family kinase signaling control leukocyte wound attraction and neutrophil reverse migration

The Journal of Cell Biology, Journal Year: 2014, Volume and Issue: 207(5), P. 589 - 598

Published: Dec. 8, 2014

Tissue damage induces early recruitment of neutrophils through redox-regulated Src family kinase (SFK) signaling in neutrophils. Redox-SFK epithelium is also necessary for wound resolution and tissue regeneration. How neutrophil-mediated inflammation resolves remains unclear. In this paper, we studied the interactions between macrophages response to zebrafish found that contact induce via neutrophil reverse migration. We redox-SFK p22phox Yes-related macrophage attraction subsequent migration Importantly, macrophage-specific reconstitution revealed redox Thus, adjacent tissues essential coordinated leukocyte repulsion pathways involve contact-mediated guidance.

Language: Английский

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Regulatory Roles of Flavonoids on Inflammasome Activation during Inflammatory Responses

Molecular Nutrition & Food Research, Journal Year: 2018, Volume and Issue: 62(13)

Published: May 18, 2018

Abstract Inflammation is an innate immune response to noxious stimuli protect the body from pathogens. Inflammatory responses consist of two main steps: priming and triggering. In priming, inflammatory cells increase expressions molecules, while in triggering, inflammasomes are activated, resulting cell death pro‐inflammatory cytokine secretion. Inflammasomes protein complexes comprising intracellular pattern recognition receptors (PRRs) (e.g., nucleotide‐binding oligomerization domain‐like (NLRs), absent melanoma 2 (AIM2), caspases‐4/5/11) pro‐caspase‐1 with or without a bipartite adaptor molecule ASC. Inflammasome activation induces pyroptosis, death, stimulates caspase‐1‐mediated secretion interleukin (IL)‐1b IL‐18. Flavonoids secondary metabolites found various plants considered as critical ingredients promoting health ameliorating disease symptoms. Anti‐inflammatory activity flavonoids underlying mechanisms have been widely studied. This review introduces current knowledge on different types their during discusses recent studies regarding anti‐inflammatory roles suppressors conditions. Understanding regulatory effects inflammasome will our flavonoid‐mediated provide new insights into development flavonoid preparations prevent treat human diseases.

Language: Английский

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