In vitro evaluation of immunobiological activity of simple mannolipids

Toxicol In Vitro. 2021 Feb:70:105014. doi: 10.1016/j.tiv.2020.105014. Epub 2020 Oct 10.

Abstract

Immunomodulation, cytotoxicity and anti-cancer activity of selected amphiphilic non-ionic (thio)alkyl α-D-mannosides (with aglycone of C6-C12) were investigated in vitro in human cervix epitheloid carcinoma cell line HeLa, murine melanoma cancer cells B16, murine lymphocytic leukemia cell line L1210, murine fibroblast cell line NIH 3 T3 and murine macrophage cell line RAW 264.7. Toxicological studies revealed structure-dependent immunobiological effectivity based on a tight interaction with relevant cells. The results demonstrated diverse immunomodulation of macrophage cell-line RAW264.7 proliferation and production of Th1 and Th2 cytokines, and induction of pro-inflammatory interleukins IL-1α, TNFα, IL-6, IL-12 and IL-17 and anti-inflammatory IL-10 following (thio)alkyl α-D-mannosides 24 and 48 h exposure. Direct application of alkyl mannosides MOC10 and MOC12 and their thio analogues MSC10 and MSC12 in reconstructed human EpiDerm™ and MOC12 and MSC12 in EpiOcular™ model assays for dermal and ocular irritation together with quantification of human proinflammatory cytokines IL-1α, TNFα, IL-6 and IL-8 culture media release was used to ascertain toxicological safety.

Keywords: (thio)Alkyl mannosides; Anticancer; Cytokines; Epiderm™ Epiocular™; RAW 264.7.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Eye / drug effects
  • Humans
  • Immunologic Factors / pharmacology*
  • Immunomodulation
  • Mannosides / pharmacology*
  • Mice
  • Models, Biological
  • Skin / drug effects

Substances

  • Antineoplastic Agents
  • Cytokines
  • Immunologic Factors
  • Mannosides