Cytokine induction of prolactin receptors mediates prolactin inhibition of nitric oxide synthesis in pulmonary fibroblasts.
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.
Corbacho
Ana M
AM
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM-Juriquilla, Apartado Postal 1-1141, Juriquilla-Querétaro, Qro. 76001, Mexico.
Macotela
Yazmin
Y
Nava
Gabriel
G
Eiserich
Jason P
JP
Cross
Carroll E
CE
Martínez de la Escalera
Gonzalo
G
Clapp
Carmen
C
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
D016207:Cytokines; D009566:Nitrates; D009573:Nitrites; D011981:Receptors, Prolactin; D019001:Nitric Oxide Synthase