Premium
CD137 ligand‐mediated reverse signals increase cell numbers and cytokine expression in murine myeloid RAW264.7 cells
Author(s) -
Lee HyeonWoo,
Kim DongKu
Publication year - 2009
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/fasebj.23.1_supplement.524.3
Subject(s) - wortmannin , ly294002 , pi3k/akt/mtor pathway , protein kinase b , microbiology and biotechnology , cytokine , chemistry , phosphorylation , tyrosine phosphorylation , tyrosine kinase , cancer research , biology , signal transduction , immunology
Cross‐linking of CD137 ligand (CD137L), a member of the TNF family, with recombinant CD137‐Fc protein (rCD137‐Fc) enhanced adherence of bone marrow‐derived macrophages, and increased the expression of ICAM‐1. In RAW 264.7 cells, a murine myeloid cell line, rCD137‐Fc not only increased adherence but also cell multiplication, in a manner comparable to LPS or M‐CSF. In addition, it up‐regulated expression of IL‐1β, IL‐1 receptor antagonist, IL‐6, COX2, Tenascin C, Neuropeptide Y and M‐CSF mRNA. Neutralization of M‐CSF by incubating the RAW264.7 cells with M‐CSF mAb did not prevent the CD137L signal‐induced viability. Viability was blocked by PP2, a Src tyrosine kinase inhibitor, rapamycin, an mTOR inhibitor and LY294002, a PI3K inhibitor, but not by Wortmannin, another PI3K inhibitor. Cross‐linking of CD137L increased phosphorylation of Akt and p70S6 kinase. The latter was blocked by PP2, rapamycin or LY294002, but not by Wortmannin, whereas phosphorylation of Akt was blocked by LY294002 or Wortmannin. These findings demonstrate that reverse signals evoked by CD137L regulate immune functions in macrophages.