Medical Hypotheses, Journal Year: 2023, Volume and Issue: 183, P. 111254 - 111254
Published: Dec. 25, 2023
Language: Английский
The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(5)
Published: Feb. 23, 2024
Mechanosensitive ion channels sense force and pressure in immune cells to drive the inflammatory response highly mechanical organs. Here, we report that Piezo1 repress group 2 innate lymphoid cell (ILC2)–driven type inflammation lungs. is induced on lung ILC2s upon activation, as genetic ablation of increases their function exacerbates development airway hyperreactivity (AHR). Conversely, agonist Yoda1 reduces ILC2-driven inflammation. Mechanistically, inhibits ILC2 cytokine secretion proliferation a KLF2-dependent manner, found engagement oxidative metabolism. Consequently, vivo treatment AHR experimental models allergic asthma. Human-circulating express induce humanized mice human AHR. Our studies define critical regulator ILC2s, propose potential activation novel therapeutic approach for
Language: Английский
Citations
10
Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(1), P. 33 - 33
Published: Jan. 14, 2025
Fungal keratitis (FK) remains a treatment challenge, necessitating new therapeutic targets. Piezo1, mechanosensitive ion channel, regulates calcium signaling and immune cell function. This study investigates its role in macrophage-mediated antifungal responses FK. Piezo1 Pyrin expression corneas bone marrow-derived macrophages (BMDMs) were assessed by RNAseq, quantitative real-time PCR (qRT-PCR), Western blot, immunofluorescence. Intracellular concentration was detected Fluo-4 AM fluorescent probe staining. Heterozygous deficiency (Piezo1+/-) mice Yoda1 performed to regulate the of Piezo1. Our investigation demonstrates elevated patients with FK infected mice. upregulation corresponded swift recruitment via limbus. Additionally, Piezo1+/- exacerbate progression infection model. Furthermore, knockdown exhibit notable reduction phagocytic capacity, accompanied an increase viable colony-forming units vitro model fungal infection. Moreover, using pharmacologic activator (Yoda1), (Ca2+) chelator BAPTA or mice, we demonstrate that activation triggers inflammasome augmented influx, which is required for protection against murine hosts. crucial innate immunity FK, enhancing macrophage recruitment, activation, inflammasome-mediated activity signaling. Using Yoda1, confirm Piezo1's clearance. Targeting offers novel strategy improve outcomes boosting function response.
Language: Английский
Citations
1
The Journal of Physiology, Journal Year: 2024, Volume and Issue: 602(18), P. 4437 - 4456
Published: April 20, 2024
Macrophages (MΦ) play pivotal roles in tissue homeostasis and repair. Their mechanical environment has been identified as a key modulator of various cell functions, MΦ mechanosensitivity is likely to be critical - particular rhythmically contracting organ such the heart. Cultured MΦ, differentiated vitro from bone marrow (MΦ
Language: Английский
Citations
7
Heliyon, Journal Year: 2024, Volume and Issue: 10(17), P. e37192 - e37192
Published: Aug. 30, 2024
In immunology, the role of macrophages extends far beyond their traditional classification as mere phagocytes; they emerge pivotal architects immune response, with function being significantly influenced by multidimensional environmental stimuli. This review investigates nuanced mechanisms which diverse external signals ranging from chemical cues to physical stress orchestrate macrophage polarization, a process that is crucial for modulation responses. By transitioning between pro-inflammatory (M1) and anti-inflammatory (M2) states, exhibit remarkable plasticity, enabling them adapt influence surroundings effectively. The exploration polarization provides compelling narrative on how these cells can be manipulated foster an environment conducive tissue repair regeneration. Highlighting cutting-edge research, this presents innovative strategies leverage dynamic interplay environment, proposing novel therapeutic avenues harness potential in regenerative medicine. Moreover, critically evaluates current challenges future prospects translating macrophage-centered laboratory clinical applications.
Language: Английский
Citations
6
Parasites & Vectors, Journal Year: 2024, Volume and Issue: 17(1)
Published: Feb. 1, 2024
Abstract Background Malaria-associated acute lung injury (MA-ALI) is a well-recognized clinical complication of severe, complicated malaria that partly driven by sequestrations infected red blood cells (iRBCs) on postcapillary induced impaired flow. In earlier studies the mechanosensitive Piezo1 channel emerged as regulator mechanical stimuli, but function and underlying mechanism impacting MA-ALI severity via sensing pulmonary flow are still not fully elucidated. Thus, present study aimed to explore role in murine MA-ALI. Methods Here, we utilized widely accepted model using C57BL/6 mice with Plasmodium berghei ANKA infection then added inhibitor (GsMTx4) model. The iRBC-stimulated Raw264.7 macrophages vitro were also targeted GsMTx4 further potential mechanism. Results Our data showed an elevation expression number + -CD68 tissues experimental mice. Compared control mice, blockage dramatically improved survival rate decreased body weight loss, peripheral parasitemia/lung parasite burden, cerebral incidence, total protein concentrations bronchoalveolar lavage fluid, wet/dry ratio, vascular leakage, pathological damage, apoptosis CD68 CD86 tissues. This was accompanied dramatic increase CD206 (M2-like subtype), upregulation anti-inflammatory cytokines (e.g. IL-4 IL-10) downregulation pro-inflammatory TNF-α IL-1β). addition, treatment remarkably intracellular iron accumulation, level 4-HNE (an activator ferroptosis) -Piezo1 -4-HNE significantly increased levels GPX4 Similarly, administration led remarkable mRNA CD206, IL-4, IL-10 GPX-4 substantial decline CD86, TNF-α, IL-1β cells. Conclusions findings indicated alleviated triggering macrophage M2 polarization subsequent responses inhibited ferroptosis tissue. suggested targeting could be promising therapeutic strategy for treating Graphical
Language: Английский
Citations
5
Kidney International, Journal Year: 2024, Volume and Issue: 106(4), P. 625 - 639
Published: July 29, 2024
Language: Английский
Citations
5
ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 21, 2025
The innate immune system is tightly regulated by a complex network of chemical signals triggered pathogens, cellular damage, and environmental stimuli. While it well-established that changes in the extracellular environment can significantly influence response to pathogens damage-associated molecules, there remains limited understanding how stimuli specifically impact activation NLRP3 inflammasome, key component immunity. Here, we demonstrated shear stress act as Signal 2 inflammasome pathway treating LPS-primed immortalized bone marrow-derived macrophages (iBMDMs) with several physiologically relevant magnitudes induce activation. We within 1.0 50 dyn/cm2 were able ASC speck formation, while was sufficient significant calcium signaling, gasdermin-D cleavage, caspase-1 activity, IL-1β secretion, all hallmarks Utilizing knockout iBMDMs, primarily activated result exposure. Quantitative polymerase chain reaction (qPCR), ELISA, small molecule inhibitor study aided us demonstrating expression Piezo1, NLRP3, gasdermin-D, IL-1β, CCL2 secretion upregulated iBMDMs treated stress. This provides foundation for further interconnected pathogenesis chronic inflammatory diseases ability play role their progression.
Language: Английский
Citations
0
BMEMat, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 18, 2025
Abstract Bone tissue is richly innervated, and the influence of nervous system on physiological pathological status bone has emerged as a significant research focus. The recent discovery skeletal interoceptive circuits further emphasizes crucial role central in control homeostasis. Skeletal interoception represents one most intricate mechanisms human body for maintaining homeostasis, it involves orchestrated efforts skeletal, nervous, immune, endocrine systems. In this review, we comprehensively introduce three primary components circuitry, including ascending pathways that perceive convey signals to system, neural process interpret these signals, descending mediate regulatory effects tissue. We also discuss how innovative therapeutic strategies can be developed modulate homeostasis by leveraging updated findings circuitry. anticipate application knowledge will lead paradigm shift field orthopaedics biomaterials.
Language: Английский
Citations
0
Progress in Biophysics and Molecular Biology, Journal Year: 2025, Volume and Issue: 196, P. 132 - 140
Published: May 6, 2025
Language: Английский
Citations
0
Mediators of Inflammation, Journal Year: 2025, Volume and Issue: 2025(1)
Published: Jan. 1, 2025
The mechanosensitive channel ‘piezo type ion component 1’ (PIEZO1) plays a regulatory role in the response of periodontal ligament fibroblasts (PDLFs) to mechanical strain that occurs during orthodontic tooth movement. In addition PDLFs, immune cells such as macrophages are also exposed stimuli. Macrophages respond with increased expression inflammatory mediators. PIEZO1 this remains elusive. To investigate effect activation, RAW264.7 were stimulated activator YODA1 without concurrent application pressure. further examine specific strain, and simultaneous inhibition either by chemical (GsMTx4) or siRNA silencing. genes proteins involved movement was examined quantitative PCR, western blot, enzyme‐linked immunosorbent assay (ELISA). Activation cytokines osteoprotegerin (Opg), which is critically bone remodeling processes. Conversely, attenuates effects stress. conclusion, our data demonstrate major contributor encountered affects factors.
Language: Английский
Citations
0