Prolactin modulation of immune and inflammatory responses.
Prolactin (PRL), a pituitary peptide hormone, is known to regulate diverse physiological functions via its effects on cellular processes such as proliferation, differentiation, and cell survival. All these activities are mediated by the PRL receptor (PRL-R), a member of the hematopoietin cytokine receptor superfamily. To understand PRL-dependent mitogenic signaling in T cells, we cloned PRL. PRL-R, one mediator of PRL signaling, signal transducer and activator of transcription (Stat) 5b, and a panel of PRL-inducible immediate early-response genes from T cells. We are employing one of these PRL-inducible genes, the transcription factor interferon regulatory factor-1 (IRF-1), a multifunctional immune regulator gene, as a tool to understand how PRL modulates T-cell proliferative responses. In investigating regulatory events along the PRL-R/Janus activating kinase (JAK)/Stat/IRF-1 signaling pathway, we show that Stat factors can activate as well as inhibit IRF-1 promoter activity and that cross talk between Stat and nuclear factor (NF)kappaB signaling pathways also regulates IRF-1 expression. In understanding how signaling pathways cross talk at the IRF-1 promoter, we obtained insights into how PRL can modulate immune and inflammatory responses. These findings have much broader implications, not only for cells in the immune system but also for other PRL-responsive cells and tissues.
Yu-Lee
Li-Yuan
LY
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA. yulee@bcm.tmc.edu
D000818:Animals; D015551:Autoimmunity; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007109:Immunity; D007249:Inflammation; D050856:Interferon Regulatory Factor-1; D008894:Milk Proteins; D016328:NF-kappa B / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics; D011388:Prolactin / Q000494:pharmacology / Q000502:physiology*; D011981:Receptors, Prolactin / Q000502:physiology; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D008894:Milk Proteins; D016328:NF-kappa B; D010750:Phosphoproteins; D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D011388:Prolactin