Waterborne microcystin-LR exposure induced chronic inflammatory response via MyD88-dependent toll-like receptor signaling pathway in male zebrafish

Sci Total Environ. 2020 Feb 1:702:134969. doi: 10.1016/j.scitotenv.2019.134969. Epub 2019 Nov 2.

Abstract

Waterborne microcystin-LR (MC-LR) released by cyanobacterial blooms in eutrophic water bodies have caused serious risk to aquatic animal and human health. In the present study, we for the first time conducted a comprehensive in vivo investigation on chronic inflammatory responses and its molecular pathways of different environmental relevant levels of MC-LR (0, 0.4, 2 and 10 μg/L) in male zebrafish (Danio rerio). The results showed that chronic MC-LR exposure caused splenic inflammatory changes including the formation of melano-macrophage centers, remarkable elevation of serum tumor necrosis factor alpha (TNFα) and interleukin 1 beta (IL1β) levels as well as significant upregulated expression of MyD88-dependent toll-like receptor (TLR/MyD88) signaling pathway genes (tlr4a, myd88, erk2, p38a, il1β and tnfα). The immunohistochemical and western blot results further validated that higher MC-LR concentrations tended to enhance the MyD88 signal. Moreover, significant decreases of serum C3 levels along with splenic c3b expression in the 10 μg/L exposure group proved that chronic MC-LR exposure could ultimately decrease the innate immunity of fish. Our findings revealed that chronic exposure of MC-LR could cause chronic inflammation through TLR/MyD88 signaling pathway and subsequently induce immune disorders in male zebrafish, which also urge us to pay more attention on the potential immunotoxicity of long-term exposure to low concentration of MC-LR.

Keywords: Gene expression; Inflammation; MC-LR; TLR/MyD88 signaling pathway; Zebrafish.

MeSH terms

  • Animals
  • Male
  • Marine Toxins
  • Microcystins / toxicity*
  • Myeloid Differentiation Factor 88 / metabolism*
  • Water Pollutants, Chemical / toxicity*
  • Zebrafish
  • Zebrafish Proteins / metabolism*

Substances

  • Marine Toxins
  • Microcystins
  • MyD88 protein, zebrafish
  • Myeloid Differentiation Factor 88
  • Water Pollutants, Chemical
  • Zebrafish Proteins
  • cyanoginosin LR