The Anti-inflammatory Effect of the CXCR4 Antagonist-N15P Peptide and Its Modulation on Inflammation-Associated Mediators in LPS-Induced PBMC

Inflammation. 2015;38(3):1374-83. doi: 10.1007/s10753-015-0109-1.


Inflammation was the important pathological process of many disease developments, but current therapeutic means for inflammatory diseases are not satisfactory. Chemokines and their receptors represent valuable targets for anti-inflammatory drug discovery. The N15P polypeptide (sequence: LGASWHRPDKCCLGY) is independently developed by our research group, it is a new CXCR4 antagonist drug derived from viral macrophage inflammatory protein-II (vMIP-II). This study aims to clarify the anti-inflammatory potency of N15P polypeptide on the lipopolysaccharide (LPS)-induced inflammation in vitro. In this study, we evaluated the anti-inflammatory effects of N15P polypeptide by the LPS-induced peripheral blood mononuclear cell (PBMC) model and measured the level of inflammatory factors (tumor necrosis factor alpha (TNF-α), IL-6, IL-8, nuclear factor kappaB (NF-κB), cyclooxygenase-2 (COX-2), Toll-like receptor 4 (TLR4), MyD88, phosphoinositide 3-kinase (PI3K), and Akt). The messenger RNA (mRNA) expressions of inflammatory factors were analyzed by real-time PCR (RT-PCR) microarray analysis, and the production of inflammatory factors was measured further by enzyme-linked immunosorbent assay (ELISA) and Western blot. The results showed that the expression of inflammatory factors (TNF-α, IL-6, IL-8, NF-κB, COX-2, TLR4, MyD88, PI3K, and Akt) was downregulated by N15P peptide, suggesting that N15P peptide has a strong inhibitory effect on the inflammatory responses induced by LPS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Cyclooxygenase 2 / metabolism
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation Mediators / pharmacology*
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Leukocytes, Mononuclear
  • Lipopolysaccharides
  • Macrophage Inflammatory Proteins / metabolism
  • Myeloid Differentiation Factor 88 / metabolism
  • Peptides / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, CXCR4 / antagonists & inhibitors
  • Toll-Like Receptor 4 / metabolism
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Inflammatory Agents
  • CXCL8 protein, human
  • CXCR4 protein, human
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • MYD88 protein, human
  • Macrophage Inflammatory Proteins
  • Myeloid Differentiation Factor 88
  • N15P peptide
  • Peptides
  • RELA protein, human
  • Receptors, CXCR4
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt