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

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Abstract

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.

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Acknowledgments

This work was supported by funding from the National Natural Science Foundation of China (no. 30872221), the Foundation for Distinguished Young Talents in Higher Education of Guangdong Province (no. 2012LYM-0023), the Medicine Science and Technology Research Foundation of Guangdong Province (no. B2012198), the Science and Technology Foundation of Administration of Traditional Chinese Medicine of Guangdong Province (no. 20131153), and the Fundamental Research Funds for the Central Universities (no. 21613340).

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  1. School of Pharmacy, Jinan University, Guangzhou, 510632, Guangdong, China

    Mo Xue-mei & Sun Han-xiao

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  1. Mo Xue-mei
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Correspondence to Mo Xue-mei.

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Xue-mei, M., Han-xiao, S. The Anti-inflammatory Effect of the CXCR4 Antagonist-N15P Peptide and Its Modulation on Inflammation-Associated Mediators in LPS-Induced PBMC. Inflammation 38, 1374–1383 (2015). https://doi.org/10.1007/s10753-015-0109-1

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