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Medhurst, A.D., Jennings, C.A., Robbins, M.J., Davis, R.P., Ellis, C., Winborn, K.Y., Lawrie, K.W., Hervieu, G., Riley, G., Bolaky, J.E., Herrity, N.C., Murdock, P. and Darker, J.G. (2003) Pharmacological and Immunohistochemical Characterization of the APJ Receptor and Its Endogenous Ligand Apelin. Journal of Neurochemistry, 84, 1162-1172. http://dx.doi.org/10.1046/j.1471-4159.2003.01587.x

has been cited by the following article:

• 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.