Effect of Shiga Toxin and Its Subunits on Cytokine Induction in Different Cell Lines

Shiga toxins (Stxs) are bacterial virulence factors produced by Shigella dysenteriae serotype 1 and Escherichia coli strains. Stxs are critical factors for the development of diseases such as severe bloody diarrhea and hemolytic uremic syndrome. Additionally, Stxs trigger the secretion of pro- inflammatory cytokines and chemokines, particularly in monocytes or macrophages. The inflammatory cytokines result in the modulation of the immune system, local inflammations and enhancement of cytotoxicity. In this study, stimulation of the pro- inflammatory cytokines IL-1α, IL-1β, IL-6, IL-8, and TNF-α was assessed by recombinant Stx (rStx) and its subunits (rStxA and rStxB). Cytokines expression at mRNA level was investigated by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) method in HeLa cells and THP1 monocyte/ macrophage cell lines. After incubation with rStx and its recombinant subunits, the expression of IL-1α, IL- 6 and IL- 8 mRNAs was strongly induced in HeLa cells. In HeLa cells, low expression of IL-1α mRNA was shown by rStxB induction. Furthermore, the expression of IL-1α and IL-1β mRNAs in undifferentiated THP1 cells was only induced by rStx. In differentiated THP1 cells, rStx and its recombinant subunits elicited the expression of IL-1α, IL-1β, IL-8 and IL- 6 mRNAs. On the other hand, expression of TNF-α mRNA was only induced by rStx. Based on the data, the profile of cytokine induction in response to the rStx, and its subunits differs depending on the cell types.