TITLE:
Synergistic interaction between C5a and NOD2 signaling in the regulation of chemokine expression in RAW 264.7 macrophages
AUTHORS:
Hui Tang, Umme Amara, Dora Tang, Mark A. Barnes, Christine McDonald, Laura E. Nagy
KEYWORDS:
Anaphylatoxin; C5L2; C5a Receptor; Complement; NOD2
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.8C,
August
19,
2013
ABSTRACT: The innate immune response is a complex process involving
multiple pathogen-recognition receptors, including toll-like receptors (TLRs)
and nucleotide-binding oligomerization domain (NOD)-like receptors. Complement
is also a critical component of innate immunity. While complement is known to
interact with TLR-mediated signals, the interactions between NOD-like receptors
and complement are not well understood. Here we report a synergistic interaction
between C5a and Nod2 signaling in
RAW 264.7 marophages. Long-term treatment with muramyl dipeptide (MDP), a
NOD2 ligand, enhanced C5a-mediated
expression of chemokine mRNAs in RAW 264.7 cells. This response was dependent
on NOD2 expression and was associated with a decrease in expression of C5L2, a receptor for C5a which acts as a negative modulator of
C5a receptor (C5aR) activity.
MDP amplified C5a-mediated
phosphorylation of p38 MAPK. Treatment of RAW264.7 cells with an inhibitor of
p38 attenuated the synergistic effects of C5aon MDP-primed cells on MIP-2, but not MCP-1, mRNA. In contrast, inhibition of
AKT prevented C5a stimulation of MCP-1, but not MIP-2, mRNA, in MDP-primed cells. Taken together,
these data demonstrated a synergistic interaction between C5a and NOD2 in the regulation of chemokine expression in macrophages,
associated with a down-regulation of C5L2,
a negative regulator of C5a receptor activity.