title: Cytokine induction of prolactin receptors mediates prolactin inhibition of nitric oxide synthesis in pulmonary fibroblasts.
abstract: Prolactin (PRL) has been implicated as a modulator of immune function, and some of its actions may be linked to NO synthesis. Because NO acts as a mediator of inflammation, we speculated that an inflammatory milieu could unmask pathways by which PRL could affect NO synthesis. Here, we show that pro-inflammatory cytokines induce the expression of PRL receptors in pulmonary fibroblasts, allowing PRL to inhibit cytokine-induced NO production and the expression of the inducible nitric oxide synthase (iNOS). Inhibition of iNOS expression by PRL correlates with the phosphorylation of STAT-5b (signal transducer and activator of transcription 5b) and the suppression of expression of IRF-1 (interferon regulatory factor 1), a transcription factor for iNOS. These results reveal previously unrecognized mechanisms by which PRL and PRL receptors may play significant modulatory roles during immune-inflammatory processes.
authors.affiliation: Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM-Juriquilla, Apartado Postal 1-1141, Juriquilla-Querétaro, Qro. 76001, Mexico.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Corbacho
authors.forename: Yazmin
authors.initials: Y
authors.lastname: Macotela
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nava
authors.forename: Jason P
authors.initials: JP
authors.lastname: Eiserich
authors.forename: Carroll E
authors.initials: CE
authors.lastname: Cross
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Martínez de la Escalera
authors.forename: Carmen
authors.initials: C
authors.lastname: Clapp
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism*; D007249:Inflammation; D008168:Lung / Q000166:cytology*; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000378:metabolism; D010766:Phosphorylation; D010902:Pituitary Gland / Q000378:metabolism; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D011981:Receptors, Prolactin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D009566:Nitrates; D009573:Nitrites; D011981:Receptors, Prolactin; D019001:Nitric Oxide Synthase