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Cell Metabolism Aug 2023This study reveals a previously uncharacterized mechanism to restrict intestinal inflammation via a regulatory RNA transcribed from a noncoding genomic locus. We...
This study reveals a previously uncharacterized mechanism to restrict intestinal inflammation via a regulatory RNA transcribed from a noncoding genomic locus. We identified a novel transcript of the lncRNA HOXA11os specifically expressed in the distal colon that is reduced to undetectable levels in colitis. HOXA11os is localized to mitochondria under basal conditions and interacts with a core subunit of complex 1 of the electron transport chain (ETC) to maintain its activity. Deficiency of HOXA11os in colonic myeloid cells results in complex I deficiency, dysfunctional oxidative phosphorylation (OXPHOS), and the production of mitochondrial reactive oxygen species (mtROS). As a result, HOXA11os-deficient mice develop spontaneous intestinal inflammation and are hypersusceptible to colitis. Collectively, these studies identify a new regulatory axis whereby a lncRNA maintains intestinal homeostasis and restricts inflammation in the colon through the regulation of complex I activity.
Topics: Animals; Mice; RNA, Long Noncoding; Colitis; Inflammation; Mitochondria; Homeostasis; Intestinal Mucosa
PubMed: 37494932
DOI: 10.1016/j.cmet.2023.06.019 -
Frontiers in Immunology 2023Chorioamnionitis, commonly referred to as intrauterine infection or inflammation, is pathologically defined by neutrophil infiltration and inflammation at the... (Review)
Review
Chorioamnionitis, commonly referred to as intrauterine infection or inflammation, is pathologically defined by neutrophil infiltration and inflammation at the maternal-fetal interface. Chorioamnionitis is the common complication during late pregnancy, which lead to a series of serious consequences, such as preterm labor, preterm premature rupture of the fetal membranes, and fetal inflammatory response syndrome. During infection, a large number of neutrophils migrate to the chorio-decidua in response to chemokines. Although neutrophils, a crucial part of innate immune cells, have strong anti-inflammatory properties, over-activating them can harm the body while also eliminating pathogens. This review concentrated on the latest studies on chorioamnionitis-related consequences as well as the function and malfunction of neutrophils. The release of neutrophil extracellular traps, production of reactive oxygen species, and degranulation from neutrophils during intrauterine infection, as well as their pathological roles in complications related to chorioamnionitis, were discussed in detail, offering fresh perspectives on the treatment of chorioamnionitis.
Topics: Female; Infant, Newborn; Pregnancy; Humans; Chorioamnionitis; Neutrophils; Inflammation; Extracellular Traps; Premature Birth
PubMed: 37475854
DOI: 10.3389/fimmu.2023.1198831 -
Science Immunology Jan 2024Pore-forming toxins (PFTs) are the largest class of bacterial toxins and contribute to virulence by triggering host cell death. Vertebrates also express endogenous...
Pore-forming toxins (PFTs) are the largest class of bacterial toxins and contribute to virulence by triggering host cell death. Vertebrates also express endogenous pore-forming proteins that induce cell death as part of host defense. To mitigate damage and promote survival, cells mobilize membrane repair mechanisms to neutralize and counteract pores, but how these pathways are activated is poorly understood. Here, we use a transposon-based gene activation screen to discover pathways that counteract the cytotoxicity of the archetypal PFT α-toxin. We identify the endolysosomal protein LITAF as a mediator of cellular resistance to PFT-induced cell death that is active against both bacterial toxins and the endogenous pore, gasdermin D, a terminal effector of pyroptosis. Activation of the ubiquitin ligase NEDD4 by potassium efflux mobilizes LITAF to recruit the endosomal sorting complexes required for transport (ESCRT) machinery to repair damaged membrane. Cells lacking LITAF, or carrying naturally occurring disease-associated mutations of LITAF, are highly susceptible to pore-induced death. Notably, LITAF-mediated repair occurs at endosomal membranes, resulting in expulsion of damaged membranes as exosomes, rather than through direct excision of pores from the surface plasma membrane. These results identify LITAF as a key effector that links sensing of cellular damage to repair.
Topics: Animals; Cell Death; Cell Membrane; Pyroptosis; Endosomes; Bacterial Toxins
PubMed: 38181093
DOI: 10.1126/sciimmunol.abq6541 -
FEMS Microbiology Reviews Nov 2023The biofilm matrix is a fortress; sheltering bacteria in a protective and nourishing barrier that allows for growth and adaptation to various surroundings. A variety of... (Review)
Review
The biofilm matrix is a fortress; sheltering bacteria in a protective and nourishing barrier that allows for growth and adaptation to various surroundings. A variety of different components are found within the matrix including water, lipids, proteins, extracellular DNA, RNA, membrane vesicles, phages, and exopolysaccharides. As part of its biofilm matrix, Pseudomonas aeruginosa is genetically capable of producing three chemically distinct exopolysaccharides - alginate, Pel, and Psl - each of which has a distinct role in biofilm formation and immune evasion during infection. The polymers are produced by highly conserved mechanisms of secretion, involving many proteins that span both the inner and outer bacterial membranes. Experimentally determined structures, predictive modelling of proteins whose structures are yet to be solved, and structural homology comparisons give us insight into the molecular mechanisms of these secretion systems, from polymer synthesis to modification and export. Here, we review recent advances that enhance our understanding of P. aeruginosa multiprotein exopolysaccharide biosynthetic complexes, and how the glycoside hydrolases/lyases within these systems have been commandeered for antimicrobial applications.
Topics: Pseudomonas aeruginosa; Biofilms; Bacterial Proteins; Polysaccharides, Bacterial
PubMed: 37884397
DOI: 10.1093/femsre/fuad060 -
Minerva Medica Jun 2024Phosphate is a key component of mineralized tissues and is also part of many organic compounds. Phosphorus homeostasis depends especially upon intestinal absorption, and... (Review)
Review
Phosphate is a key component of mineralized tissues and is also part of many organic compounds. Phosphorus homeostasis depends especially upon intestinal absorption, and renal excretion, which are regulated by various hormones, such as PTH, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23. In this review we provide an update of several genetic disorders that affect phosphate transporters through cell membranes or the phosphate-regulating hormones, and, consequently, result in hypophosphatemia.
Topics: Humans; Hypophosphatemia; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Parathyroid Hormone; Phosphates; Vitamin D; Klotho Proteins; Phosphate Transport Proteins; PHEX Phosphate Regulating Neutral Endopeptidase; Intestinal Absorption; Glucuronidase; Phosphorus
PubMed: 38727708
DOI: 10.23736/S0026-4806.24.09198-5