Prolactin induced production of cytokines in macrophages involves Ca++ and p42/44 MAP kinase signaling pathway.
The immunomodulatory properties of prolactin (PRL) are well recognized. Recently, we have reported the activation and enhanced production of nitric oxide by macrophages on treatment with PRL. The involvement of protein tyrosine kinases, MAP kinases and Ca++ signaling in the enhanced nitric oxide production by macrophages on PRL treatment was also established. In the present study, it has been observed that PRL induces the intracellular release of Ca++; activates protein kinase C (PKC)-8 and p42/44 MAP kinase. The activation of PKC-delta was found to be inhibited by Pertussis toxin (PTX) (Galpha1-protein inhibitor) and H7 (PKC inhibitor). Pretreatment of macrophages with PTX, H7, TMB8 (intracellular Ca++ immobilizer) significantly down regulated the PRL induced intracellular Ca++ release and the activation of p42/44 MAP kinases. The involvement of Ca++ signaling and p42/44 MAP kinase in regulation of PRL induced IL-1beta and TNF-alpha production by macrophages has also been investigated. PRL is observed to induce the expression of transcription factors phospho-Elk-1, c-fos and phospho-c-myc. These observations clearly suggest the involvement of PKC-delta/Ca++/p42-44 MAP kinase cascade in PRL induced activation of murine peritoneal macrophages.
Sodhi
Ajit
A
Faculty of Science, School of Biotechnology, Banaras Hindu University, Varanasi 221005, India. ajit.sodhi@lycos.com
Tripathi
Anurag
A
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005562:Formazans / Q000378:metabolism; D007700:Kinetics; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011388:Prolactin / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000378:metabolism
D016207:Cytokines; D005562:Formazans; D013778:Tetrazolium Salts; C079782:MTT formazan; D011388:Prolactin