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Shigeyuki Obara, Sumio Akifusa, Wataru Ariyoshi, Toshinori Okinaga, Michihiko Usui, Keisuke Nakashima, Tatsuji Nishihara


Department of Oral Health Management, Kyushu Dental University, Fukuoka, Japan.
Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Fukuoka, Japan.
Division of Periodontology, Department of Oral Function, Kyushu Dental University, Fukuoka, Japan.


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.


Apelin, Macrophage, Inflammation

Cite this paper

Obara, S. , Akifusa, S. , Ariyoshi, W. , Okinaga, T. , Usui, M. , Nakashima, K. and Nishihara, T. (2014) Pyroglutamated Apelin-13 Inhibits Lipopolysaccharide-Induced Production of Pro-Inflammatory Cytokines in Murine Macrophage J774.1 Cells. Modern Research in Inflammation, 3, 59-66. doi: 10.4236/mri.2014.32007.

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