Modulation of Pro-Oxidant and Pro-Inflammatory Activities of M1 Macrophages by the Natural Dipeptide Carnosine

Claudia G. Fresta, Annamaria Fidilio, Giacomo Lazzarino, Nicolò Musso, Margherita Grasso, Sara Merlo, Angela M. Amorini, Claudio Bucolo, Barbara Tavazzi, Giuseppe Lazzarino, Susan M. Lunte, Filippo Caraci, Giuseppe Caruso

Research output: Contribution to journalArticle

Abstract

Carnosine is a natural endogenous dipeptide widely distributed in mammalian tissues, existing at particularly high concentrations in the muscles and brain and possesses well-characterized antioxidant and anti-inflammatory activities. In an in vitro model of macrophage activation, induced by lipopolysaccharide + interferon-gamma (LPS + IFN-γ), we here report the ability of carnosine to modulate pro-oxidant and pro-inflammatory activities of macrophages, representing the primary cell type that is activated as a part of the immune response. An ample set of parameters aimed to evaluate cytotoxicity (MTT assay), energy metabolism (HPLC), gene expressions (high-throughput real-time PCR (qRT-PCR)), protein expressions (western blot) and nitric oxide production (qRT-PCR and HPLC), was used to assess the effects of carnosine on activated macrophages challenged with a non cytotoxic LPS (100 ng/mL) + IFN-γ (600 U/mL) concentration. In our experimental model, main carnosine beneficial effects were: (1) the modulation of nitric oxide production and metabolism; (2) the amelioration of the macrophage energy state; (3) the decrease of the expressions of pro-oxidant enzymes (Nox-2, Cox-2) and of the lipid peroxidation product malondialdehyde; (4) the restoration and/or increase of the expressions of antioxidant enzymes (Gpx1, SOD-2 and Cat); (5) the increase of the transforming growth factor-β1 (TGF-β1) and the down-regulation of the expressions of interleukins 1β and 6 (IL-1β and IL-6) and 6) the increase of the expressions of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1). According to these results carnosine is worth being tested in the treatment of diseases characterized by elevated levels of oxidative stress and inflammation (atherosclerosis, cancer, depression, metabolic syndrome, and neurodegenerative diseases).

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume21
Issue number3
DOIs
Publication statusPublished - Jan 25 2020

    Fingerprint

Keywords

  • antioxidants
  • carnosine
  • energy metabolism
  • inflammation
  • M1 macrophages
  • nitric oxide
  • oxidative stress

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Fresta, C. G., Fidilio, A., Lazzarino, G., Musso, N., Grasso, M., Merlo, S., Amorini, A. M., Bucolo, C., Tavazzi, B., Lazzarino, G., Lunte, S. M., Caraci, F., & Caruso, G. (2020). Modulation of Pro-Oxidant and Pro-Inflammatory Activities of M1 Macrophages by the Natural Dipeptide Carnosine. International Journal of Molecular Sciences, 21(3). https://doi.org/10.3390/ijms21030776