cGAS/STING pathway modulation in polyhexamethyleneguanidine phosphate-induced immune dysregulation and pulmonary fibrosis using human monocytic cells (THP-1) and male C57BL/6 mice DOI
Jin Kyung Seok,

Jung in Jee,

Minwoo Jeon

et al.

Journal of Toxicology and Environmental Health, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 13

Published: Nov. 28, 2024

Polyhexamethyleneguanidine phosphate (PHMG), a widely used antimicrobial agent, has been implicated in humidifier disinfectant-associated lung injuries (HDLI). PHMG exposure suppressed interferon regulatory factor 3 (IRF3) activation and interferon-β (IFN-β) expression induced by cGAS agonist or STING human monocytic cells (THP-1), which are known to transition alveolar macrophages during pulmonary fibrosis development. However, the mechanisms underlying PHMG-induced toxicity remain unclear. Thus, it was of interest investigate effects on innate immune system male C57BL/6 mouse, focusing cyclic GMP-AMP synthase (cGAS)/stimulator genes (STING) pathway potential role fibrosis. Intratracheal administration (1 2 mg/kg) mice resulted fibrosis, as evidenced H&E staining with Szapiel scoring, Masson's trichrome Ashcroft increased mRNA levels TGF-β collagen type I. Interestingly, lower dose enhanced IFN-β production lungs, whereas higher decreased levels, indicating biphasic effect that initially promotes inflammation but ultimately impairs host defense mechanisms, leading Our findings demonstrate critical cGAS/STING mouse injury suggest targeting this might serve therapeutic strategy for treating

Language: Английский

Origin and Function of Anti-Interferon Type I Viral Proteins DOI Creative Commons
Marta Acchioni, Chiara Acchioni, John Hiscott

et al.

Virology, Journal Year: 2025, Volume and Issue: 605, P. 110456 - 110456

Published: Feb. 20, 2025

Language: Английский

Citations

0
Advances in the prerequisite and consequence of STING downstream signalosomes DOI Creative Commons
Xinliang Lu, Xiaobing Li, Lili Li

et al.

Medical Review, Journal Year: 2024, Volume and Issue: 4(5), P. 435 - 451

Published: May 7, 2024

Abstract The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is an evolving DNA-sensing mechanism involved in innate immunity and pathogen defense that has been optimized while remaining conserved. Aside from recognizing pathogens through conserved motifs, these receptors also detect aberrant or misplaced self-molecules as possible signs perturbed homeostasis. Upon binding external self-derived DNA, a mobile secondary messenger 2′3′-cyclic (cGAMP) produced by cGAS turn activates its adapter STING the endoplasmic reticulum (ER). Resting-state activated protein finely restricted multiple degradation machineries. post-translational changes protein, along with regulatory machinery secret routes, limit onset, strength sustention signal. experiences conformational shift relocates TBK1 ER to perinuclear vesicles containing transcription factors, provoking activity IRF3/IFN-I NF-κB pathways, well initiate number cellular processes have shown alter immune landscape cancer, such autophagy, NLRP3 inflammasome, stress, cell death. signal thus serves potent activator for mobilization yet triggers immune-mediated pathology tissues. Recent advances established vital role surveillance tumorigenic process. This review provides overview disparate outcomes cancer attributed actions pleiotropic coordinated downstream signalosomes, underlying mechanisms function pathologies, providing therapeutic implications new approaches hunt next generation immunotherapy base on STING.

Language: Английский

Citations

2
Single-cell transcriptome and T cell receptor profiling of the tuberculin skin test DOI
Carolin T. Turner, Joshua Rosenheim, Clare Thakker

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 29, 2024

Abstract The tuberculin skin test (TST) is a cutaneous delayed hypersensitivity reaction to antigen from Mycobacterium tuberculosis (Mtb). We provide the first single cell sequencing characterisation of human TST reaction, based on suction blisters induced at site day 2 in 31 individuals. Integrated RNA and TCR showed immune response be dominated by T cells, with smaller populations NK cells myeloid cells. comprised CD4, CD8, gamma/delta 50% all identified as cytotoxic 14% regulatory. Interferon gamma gene expression was strongest CD8 distinct CD4 helper lineages could not unambiguously this time point. Amongst 63% displayed antimicrobial 28% were functionally polarised towards presentation higher levels HLA class expression. derived validated transcriptional signatures for types cellular functions relevant landscape TST. These data help improve our understanding Mtb enable further exploration bulk transcriptomic through context-specific deconvolution.

Language: Английский

Citations

0
cGAS/STING pathway modulation in polyhexamethyleneguanidine phosphate-induced immune dysregulation and pulmonary fibrosis using human monocytic cells (THP-1) and male C57BL/6 mice DOI
Jin Kyung Seok,

Jung in Jee,

Minwoo Jeon

et al.

Journal of Toxicology and Environmental Health, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 13

Published: Nov. 28, 2024

Polyhexamethyleneguanidine phosphate (PHMG), a widely used antimicrobial agent, has been implicated in humidifier disinfectant-associated lung injuries (HDLI). PHMG exposure suppressed interferon regulatory factor 3 (IRF3) activation and interferon-β (IFN-β) expression induced by cGAS agonist or STING human monocytic cells (THP-1), which are known to transition alveolar macrophages during pulmonary fibrosis development. However, the mechanisms underlying PHMG-induced toxicity remain unclear. Thus, it was of interest investigate effects on innate immune system male C57BL/6 mouse, focusing cyclic GMP-AMP synthase (cGAS)/stimulator genes (STING) pathway potential role fibrosis. Intratracheal administration (1 2 mg/kg) mice resulted fibrosis, as evidenced H&E staining with Szapiel scoring, Masson's trichrome Ashcroft increased mRNA levels TGF-β collagen type I. Interestingly, lower dose enhanced IFN-β production lungs, whereas higher decreased levels, indicating biphasic effect that initially promotes inflammation but ultimately impairs host defense mechanisms, leading Our findings demonstrate critical cGAS/STING mouse injury suggest targeting this might serve therapeutic strategy for treating

Language: Английский

Citations

0