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Novel Noncompetitive IL-1 Receptor-Biased Ligand Prevents Infection- and Inflammation-Induced Preterm Birth.
Nadeau-Vallée, Mathieu; Quiniou, Christiane; Palacios, Julia; Hou, Xin; Erfani, Atefeh; Madaan, Ankush; Sanchez, Mélanie; Leimert, Kelycia; Boudreault, Amarilys; Duhamel, François; Rivera, José Carlos; Zhu, Tang; Noueihed, Baraa; Robertson, Sarah A; Ni, Xin; Olson, David M; Lubell, William; Girard, Sylvie; Chemtob, Sylvain.
Afiliación
  • Nadeau-Vallée M; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Ophthalmology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Departm
  • Quiniou C; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Ophthalmology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada;
  • Palacios J; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Ophthalmology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada;
  • Hou X; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Ophthalmology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada;
  • Erfani A; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Ophthalmology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada;
  • Madaan A; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Ophthalmology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Departm
  • Sanchez M; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Ophthalmology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Departm
  • Leimert K; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta TG6 2S2, Canada; Department of Pediatrics, University of Alberta, Edmonton, Alberta TG6 2S2, Canada; Department of Physiology, University of Alberta, Edmonton, Alberta TG6 2S2, Canada;
  • Boudreault A; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Ophthalmology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada;
  • Duhamel F; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Ophthalmology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Departm
  • Rivera JC; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Ophthalmology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Maisonn
  • Zhu T; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Ophthalmology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada;
  • Noueihed B; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Ophthalmology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada;
  • Robertson SA; Department of Obstetrics and Gynecology, University of Adelaide, Adelaide, South Australia 5005, Australia;
  • Ni X; Department of Obstetrics and Gynecology, Second Military Medical University, Shanghai 200433, China;
  • Olson DM; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta TG6 2S2, Canada; Department of Pediatrics, University of Alberta, Edmonton, Alberta TG6 2S2, Canada; Department of Physiology, University of Alberta, Edmonton, Alberta TG6 2S2, Canada;
  • Lubell W; Department of Chemistry, University of Montreal, Montreal, Quebec H3C 3J7, Canada;
  • Girard S; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Obstetrics and Gynecology, CHU Sainte-Justine Research Centre, Montreal, Quebec H3T 1C5, Canada; and Department of Physiology, CHU Sainte-Justine Research Centre, Montreal, Quebec H3T 1C5, C
  • Chemtob S; Department of Pediatrics, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Ophthalmology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Department of Pharmacology, CHU Sainte-Justine Research Center, Montreal, Quebec H3T 1C5, Canada; Maisonn
J Immunol ; 195(7): 3402-15, 2015 Oct 01.
Article en En | MEDLINE | ID: mdl-26304990
Preterm birth (PTB) is firmly linked to inflammation regardless of the presence of infection. Proinflammatory cytokines, including IL-1ß, are produced in gestational tissues and can locally upregulate uterine activation proteins. Premature activation of the uterus by inflammation may lead to PTB, and IL-1 has been identified as a key inducer of this condition. However, all currently available IL-1 inhibitors are large molecules that exhibit competitive antagonism properties by inhibiting all IL-1R signaling, including transcription factor NF-κB, which conveys important physiological roles. We hereby demonstrate the efficacy of a small noncompetitive (all-d peptide) IL-1R-biased ligand, termed rytvela (labeled 101.10) in delaying IL-1ß-, TLR2-, and TLR4-induced PTB in mice. The 101.10 acts without significant inhibition of NF-κB, and instead selectively inhibits IL-1R downstream stress-associated protein kinases/transcription factor c-jun and Rho GTPase/Rho-associated coiled-coil-containing protein kinase signaling pathways. The 101.10 is effective at decreasing proinflammatory and/or prolabor genes in myometrium tissue and circulating leukocytes in all PTB models independently of NF-κB, undermining NF-κB role in preterm labor. In this work, biased signaling modulation of IL-1R by 101.10 uncovers a novel strategy to prevent PTB without inhibiting NF-κB.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Nacimiento Prematuro / Proteínas Quinasas JNK Activadas por Mitógenos / Proteínas Quinasas p38 Activadas por Mitógenos / Inflamación Tipo de estudio: Prognostic_studies Límite: Animals / Pregnancy Idioma: En Revista: J Immunol Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Nacimiento Prematuro / Proteínas Quinasas JNK Activadas por Mitógenos / Proteínas Quinasas p38 Activadas por Mitógenos / Inflamación Tipo de estudio: Prognostic_studies Límite: Animals / Pregnancy Idioma: En Revista: J Immunol Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos