PLIF induces IL-10 production in monocytes: a calmodulin-p38 mitogen-activated protein kinase-dependent pathway.
Recently, we reported the cloning and preliminary characterization of a novel human immunomodulator named PLIF (placenta immunomodulatory ferritin). PLIF has a unique molecular structure, which is composed of a ferritin heavy chain-like domain and a novel cytokine-like domain called C48. Both intact molecule and C48 inhibit T cell proliferation following allogeneic or anti-CD3 stimuli. PLIF is localized at the fetal-maternal interface of human placenta and might play a role in down-modulating the maternal immune reaction toward the embryo. The inhibitory effect of PLIF on T cell activation can be direct, indirect through cytokine mediators, or both. In the present study we investigated the possible indirect effects of PLIF by using its bioactive domain C48. Measurement of various cytokines revealed that C48, predominantly, induce pronounced and rapid IL-10 production in monocytes, which is immune activation-independent. Further, we discovered that C48-induced IL-10 production is mediated through a calcium/calmodulin-p38 mitogen-activated protein (MAP) kinase signaling pathway. However, extracellular signal-related kinases1,2 (ERK1,2), also activated by C48 stimulation, exhibited a limiting effect on IL-10 production.
Zahalka
Muayad A
MA
Laboratory of Molecular Immunology, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Rabin Medical Center, Petach-Tikva 49100, Israel.
Barak
Vivian
V
Traub
Leonid
L
Moroz
Chaya
C
D001665:Binding Sites / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D018920:Coculture Techniques; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005293:Ferritins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis*; D007546:Isoquinolines / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010088:Oxidoreductases; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011257:Pregnancy Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D002147:Calmodulin; D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D008301:Maleimides; D010446:Peptide Fragments; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; D013449:Sulfonamides; D016753:Interleukin-10; D004533:Egtazic Acid; C017967:W 7; D005293:Ferritins; C454461:FTH1 protein, human; D010088:Oxidoreductases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C070515:bisindolylmaleimide I; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium