title: Liposomal retinoic acids modulate asthma manifestations in mice.
abstract: Signaling of all-trans retinoic acid (ATRA) through nuclear retinoid acid (RA) receptors regulates several biological functions in airway epithelial cells, eosinophils, and immune cells, yet its impact on different in vivo aspects of pulmonary allergic reaction remains elusive. We compared the effect of a treatment with liposomally encapsulated ATRA (Lipo-ATRA) in a mouse model of ovalbumin (OVA)-induced T helper (Th) 2-type responses and airway remodeling. Daily intraperitoneal injections of 10 mg/kg Lipo-ATRA, at the time of each of the 2 systemic sensitizing injections, increased OVA-induced Immunoglobulin E synthesis, bronchoalveolar lavage (BAL) eosinophilia, and accumulation of IL-5, transforming-growth factor beta1, fibronectin, eotaxin/chemokine (C-C motif) ligand 11 (eotaxin/CCL11) and regulated upon activation, normal T expressed and secreted chemokine (C-C motif) ligand 5. In contrast, Lipo-ATRA, administered during each of the 4 intranasal OVA challenges, did not affect these variables. Regardless of the treatment regimen, Lipo-ATRA augmented mucin levels in BAL fluid and reduced lung total collagen content. In vitro incubation of mouse splenocytes or purified spleen cluster of differentiation (CD) 4-positive T lymphocytes, with ATRA, increased, respectively, OVA- and anti-CD 3 antibody-induced IL-4 and IL-5 production and inhibited IFNgamma release. These findings demonstrate that, when given during systemic sensitization, Lipo-ATRA exacerbates allergic immune and inflammatory responses, most likely by promoting Th2 development.
authors.affiliation: Inserm U700 and Université Paris 7, Paris, F-75018 France.
authors.forename: Marielle
authors.initials: M
authors.lastname: Maret
authors.forename: Claude
authors.initials: C
authors.lastname: Ruffie
authors.forename: Brigitte
authors.initials: B
authors.lastname: Periquet
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Campo
authors.forename: Moise
authors.initials: M
authors.lastname: Menevret
authors.forename: Aurélie
authors.initials: A
authors.lastname: Phelep
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Dziewiszek
authors.forename: Anne
authors.initials: A
authors.lastname: Druilhe
authors.forename: Marina
authors.initials: M
authors.lastname: Pretolani
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000032:analysis; D007073:Immunoglobulin E; D008081:Liposomes; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D012176:Retinoids / Q000097:blood; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013997:Time Factors; D014212:Tretinoin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D008081:Liposomes; D012176:Retinoids; D007073:Immunoglobulin E; D014212:Tretinoin; D010047:Ovalbumin; D003094:Collagen