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PLIF induces IL‐10 production in monocytes: a calmodulin‐p38 mitogen‐activated protein kinase‐dependent pathway
Author(s) -
Zahalka Muayad A.,
Barak Vivian,
Traub Leonid,
Moroz Chaya
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0960fje
Subject(s) - microbiology and biotechnology , protein kinase a , p38 mitogen activated protein kinases , cytokine , chemistry , kinase , immune system , signal transduction , calmodulin , extracellular , biology , biochemistry , immunology , enzyme
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.