title: Prmt2 regulates the lipopolysaccharide-induced responses in lungs and macrophages.
abstract: Precise control of the LPS stimulation in the lung modulates inflammation and airway hyperresponsiveness involving the well-known TLR4/NF-κB pathway. As a consequence, the expression and secretion of proinflammatory cytokines is tightly regulated with the recruitment of neutrophils. Changes in the LPS-induced responses have been observed in the Prmt2-Col6a1 monosomic model, suggesting the presence of dosage-sensitive genes controlling LPS pathway in the mouse. In this article, we report that the Prmt2 regulates the LPS-induced lung responses in lungs and macrophages. We demonstrate that Prmt2 gene dosage influences the lung airway hyperresponsiveness, the recruitment of neutrophils, and the expression of proinflammatory cytokines, such as IL-6 and TNF-α. In addition, Prmt2 loss of function also altered the nuclear accumulation of NF-κB in stimulated macrophages. Prmt2 should be considered as a new member of the NF-κB pathway controlling LPS-induced inflammatory and lung responses in a dosage-dependent manner, certainly through regulating nuclear accumulation of NF-κB as shown already in fibroblasts.
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Génétique Biologie Moléculaire et Cellulaire, INSERM, Université de Strasbourg, Unité Mixte de Recherche 7104, 67404 Illkirch, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Dalloneau
authors.forename: Patricia Lopes
authors.initials: PL
authors.lastname: Pereira
authors.forename: Véronique
authors.initials: V
authors.lastname: Brault
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Nabel
authors.forename: Yann
authors.initials: Y
authors.lastname: Hérault
mesh_terms: D000818:Animals; D024142:Collagen Type VI / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D006580:Genetic Carrier Screening / Q000379:methods; D018836:Inflammation Mediators / Q000502:physiology*; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D008168:Lung / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008780:Methyltransferases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology; D011484:Protein-Arginine N-Methyltransferases; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: C540085:Col6a1 protein, mouse; D024142:Collagen Type VI; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D008780:Methyltransferases; C553397:PRMT2 protein, mouse; D011484:Protein-Arginine N-Methyltransferases