Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Adv Biol Regul. 2016 May;61:68-79. doi: 10.1016/j.jbior.2015.11.004. Epub 2015 Nov 28.

Phospholipase C δ1 in macrophages negatively regulates TLR4-induced proinflammatory cytokine production and Fcγ receptor-mediated phagocytosis.

Author information

1
Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
2
Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; AMED-CREST, AMED, Tokyo, Japan.
3
Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; AMED-CREST, AMED, Tokyo, Japan. Electronic address: kfukami@toyaku.ac.jp.

Abstract

Macrophages are key players in the innate immune response. Turnover of phosphoinositides (PI), particularly phosphatidylinositol 4,5 bisphosphate (PI(4,5)P2), has been implicated in macrophage functions such as toll-like receptor (TLR)-mediated cytokine production and phagocytosis. However, PI metabolizing enzymes responsible for macrophage functions are not well defined. The phospholipase C (PLC) family of enzymes is critical in PI(4,5)P2 turnover. In this study, we investigated the role of PLCδ1, a prototype PLC, in macrophages on the expression of inflammation-associated genes and phagocytosis. Lipopolysaccharides (LPS) signal through TLR4 to produce proinflammatory cytokines such as interleukin (IL)-1β. LPS stimulation of both RAW264.7 murine macrophages and murine bone marrow-derived macrophages resulted in lower PLCδ1 mRNA and protein expression levels, compared to that in the control. Using chemical inhibitor compounds, we demonstrated that the up-regulation of p38 MAPK activity led to down-regulation of PLCδ1 mRNA expression in macrophages. PLCδ1 reduction by RNAi or gene deletion resulted in greater LPS-induced IL-1β expression than that observed in the control siRNA-treated cells, without increasing TLR4 cell surface expression. PLCδ1 also negatively regulated LPS-induced cell spreading. Analysis of Fcγ receptor-mediated phagocytosis demonstrated an increased phagocytosis index after PLCδ1 knockdown in RAW264.7 cells. Conversely, overexpression of PLCδ1 reduced phagocytosis whereas catalytic inactive PLCδ1 had no effect. Altered levels of PLCδ1 affected the binding of opsonized latex beads with cells, rather than the phagocytic activity. Taken together, the data suggest that PLCδ1 negatively regulates LPS-induced production of IL-1β and Fcγ receptor-mediated phagocytosis in macrophages.

KEYWORDS:

Macrophage; Phagocytosis; Phosphoinositide; Phospholipase C; Toll-like receptor

PMID:
26643908
DOI:
10.1016/j.jbior.2015.11.004
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center