Prolactin modulates IL-8 production induced by porins or LPS through different signaling mechanisms.
Prolactin (PRL) induces cell proliferation and cell differentiation through the well-known mitogen-activated protein kinases (MAPKs) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways, depending on the cell line. MAPKs play a central role in signaling transduction mechanisms that transmit mitogenic or differentiation signals from an activated receptor to the intracellular machinery. All of the cytokine receptors that activate the JAK/STAT pathway also activate the MAPK pathway. The aim of the present study was to delineate the signal pathways implicated in IL-8 release by THP-1 cells, pretreated with PRL, after stimulation with either lipopolysaccharide (LPS) or porins from Salmonella enterica serovar Typhimurium. PRL activates the JAK2/STAT1-3 signaling pathway, while LPS or porins from S. enterica serovar Typhimurium does not induce any phosphorylation of this pathway. However, in THP-1 cells, the combination of PRL followed by either S. enterica serovar Typhimurium LPS or porins produced a greater MEK1-MEK2/MAPKs activation response than treatment with PRL alone. Similarly, PRL pretreatment of THP-1 cells resulted in an increase in IL-8 release in response to stimulation with either LPS or porins. This additive effect on IL-8 release was reduced when the cells were also treated with PD-098059, a selective inhibitor of the MEK1 activator and the MAPK cascade, or SB203580, a specific inhibitor of the p38 pathway, or AG490, a specific JAK/STAT pathway inhibitor, providing evidence that there are different signal pathways activated which have a cumulative effect.
D'Isanto
Marina
M
Dipartimento di Patologia Generale, Facoltà di Medicina e Chirurgia, Seconda Università di Napoli, Via De Crecchio 7, 80138 Naples, Italy.
Vitiello
Mariateresa
M
Raieta
Katia
K
Galdiero
Massimiliano
M
Galdiero
Marilena
M
D015153:Blotting, Western; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018272:Porins / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012486:Salmonella typhimurium / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism
D016207:Cytokines; D016209:Interleukin-8; D008070:Lipopolysaccharides; D018272:Porins; D015534:Trans-Activators; D011388:Prolactin; D007770:L-Lactate Dehydrogenase; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases