Prolactin-induced production of cytokines in macrophages in vitro involves JAK/STAT and JNK MAPK pathways.
Macrophages play a crucial role in host immunosurveillance against pathogens and malignancies. The enhanced productions of pro-inflammatory cytokines are central to the regulatory role of macrophages and induction of robust immune response. The excessive inflammatory response of macrophages can result into pathological conditions in host. We have previously reported that prolactin (PRL) induces the production of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha in murine peritoneal macrophages. It was suggested that protein tyrosine kinases (PTKs), mitogen-activated protein kinases (MAPKs) and Ca(++) signaling were involved in the NO production by macrophages on PRL treatment. In this manuscript, we investigated the role of PTKs [Janus kinase (JAK) 2 and phosphoinositide 3-kinase (PI3K)] and c-Jun N-terminal kinase (JNK) MAPK in PRL-induced activation of murine peritoneal macrophages. It is reported that PRL-induced activation of macrophages in vitro is dependent on JAK/signal transducers and activators of transcription (STAT) and JNK MAPK-signaling pathways. It is observed that pre-treatment of macrophages with JNK inhibitor, SP600125; tyrosine kinase inhibitor, genistein; PI3K inhibitor, Wortmannin and JAK2 inhibitor, AG490 inhibited the phosphorylation of JNK MAPK. Further, pre-treatment of macrophages with SP600125 inhibited the PRL-induced production of IFN-gamma and TNF-alpha. AG490, inhibitor of JAK2, down-regulated transcription factors c-jun and STAT1 and inhibited the PRL-induced IFN-gamma, TNF-alpha, IL-1 beta and IL-12p40 production in macrophages.
Tripathi
Anurag
A
School of Biotechnology, Faculty of Science, Banaras Hindu University, Varanasi 221005, India.
Sodhi
Ajit
A
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D020672:I-kappa B Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology*; D053612:Janus Kinases / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011388:Prolactin / Q000494:pharmacology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*
D016207:Cytokines; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D016755:Proto-Oncogene Proteins c-jun; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D011388:Prolactin; D019869:Phosphatidylinositol 3-Kinases; D053612:Janus Kinases; D048031:JNK Mitogen-Activated Protein Kinases