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Peptidoglycan and lipopolysaccharide activate PLCγ2, leading to enhanced cytokine production in macrophages and dendritic cells
Author(s) -
Aki Daisuke,
Minoda Yasumasa,
Yoshida Hideyuki,
Watanabe Satoko,
Yoshida Ryoko,
Takaesu Giichi,
Chinen Takatoshi,
Inaba Toshiya,
Hikida Masaki,
Kurosaki Tomohiro,
Saeki Kazuko,
Yoshimura Akihiko
Publication year - 2008
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2007.01159.x
Subject(s) - microbiology and biotechnology , biology , tlr2 , tlr4 , phosphorylation , peptidoglycan , kinase , tyrosine phosphorylation , signal transduction , trif , toll like receptor , innate immune system , receptor , biochemistry , enzyme
In macrophages and monocytes, microbial components trigger the production of pro‐inflammatory cytokine through Toll‐like receptors (TLRs). Although major TLR signaling pathways are mediated by serine/threonine kinases, including TAK1, IKK and MAP kinases, tyrosine phosphorylation of intracellular proteins by TLR ligands has been suggested in a number of reports. Here, we demonstrated that peptidoglycan (PGN) of a Gram‐positive bacterial cell wall component, a TLR2 ligand and lipopoysaccharide (LPS) of a Gram‐positive bacterial component, a TLR4 ligand induced tyrosine phosphorylation of phospholipase Cγ‐2 (PLCγ2), leading to intracellular free Ca 2+ mobilization in bone marrow‐derived macrophages (BMMφ) and bone marrow‐derived dendritic cells (BMDC). PGN‐ and LPS‐induced Ca 2+ mobilization was not observed in BMDC from PLCγ2 knockout mice. Thus, PLCγ2 is essential for TLR2 and TLR4‐mediated Ca 2+ flux. In PLCγ2‐knockdown cells, PGN‐induced IκB‐α phosphorylation and p38 activation were reduced. Moreover, PLCγ2 was necessary for the full production of TNF‐α and IL‐6. These data indicate that the PLCγ2 pathway plays an important role in bacterial ligands‐induced activation of macrophages and dendritic cells.