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

• Published in: Inflammation Vol. 38; no. 3; pp. 1374 - 1383
• Main Authors: Mo, Xue-mei, Sun, Han-xiao
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2015; Springer Nature B.V
• Subjects: Active Transport, Cell Nucleus - drug effects; Anti-Inflammatory Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Cyclooxygenase 2 - metabolism; Humans; Immunology; Inflammation - drug therapy; Inflammation - immunology; Inflammation Mediators - pharmacology; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Internal Medicine; Leukocytes, Mononuclear; Lipopolysaccharides; Macrophage Inflammatory Proteins - metabolism; Myeloid Differentiation Factor 88 - metabolism; Pathology; Peptides - pharmacology; Pharmacology/Toxicology; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Receptors, CXCR4 - antagonists & inhibitors; Rheumatology; Toll-Like Receptor 4 - metabolism; Transcription Factor RelA - metabolism; Tumor Necrosis Factor-alpha - metabolism; N15P peptide; proinflammatory cytokines; inflammation; LPS
• ISSN: 0360-3997; 1573-2576; 1573-2576
• 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.