TITLE:
Pyroglutamated Apelin-13 Inhibits Lipopolysaccharide-Induced Production of Pro-Inflammatory Cytokines in Murine Macrophage J774.1 Cells
AUTHORS:
Shigeyuki Obara, Sumio Akifusa, Wataru Ariyoshi, Toshinori Okinaga, Michihiko Usui, Keisuke Nakashima, Tatsuji Nishihara
KEYWORDS:
Apelin, Macrophage, Inflammation
JOURNAL NAME:
Modern Research in Inflammation,
Vol.3 No.2,
May
6,
2014
ABSTRACT: Apelin, recently
identified as an endogenous ligand of the orphan G protein-coupled receptor
APJ, has multiple pathophysiological properties. In the present study, we
investigated whether pyroglutamated apelin-13 ([Pyr1]-apelin-13), the most
highly active isoform among the mature apelin peptide family, modulates the
effect of bacterial lipopolysaccharide (LPS) on cytokine induction in a murine
macrophage-like cell line, J774.1 cells. J774.1 cells expressed the APJ protein
in a stationary state, and the expression of APJ was not affected by LPS
stimulation. No significant effect of [Pyr1]-apelin-13 treatment alone was
observed on the proliferation or cytokine production of J774.1 cells in the
stationary state. However, prior to LPS stimulation, pretreatment with [Pyr1]apelin-13
for 16 h significantly diminished mRNA expression and protein secretion of
inflammatory cytokine interleukin-6, which was confirmed by RT-PCR and ELISA,
respectively. Western blot analysis revealed that the phosphorylation of p38
mitogen-activated protein kinase and c-Jun N-terminal kinase, but not
extracellular signal-regulated kinase, which was induced by LPS, significantly
decreased in [Pyr1]-apelin-13-pretreated J774.1 cells compared with untreated
cells. These observations suggest that [Pyr1]-apelin-13 functions as a negative
regulator of LPS-mediated pro-inflammatory responses in macrophages.