Insulin-like growth factor 1 receptor and insulin receptor mediate AP-1-activation in enterocytes stimulated with parasite antigens

Question Schistosomiasis is a parasitic infection, which affects at least 230 million people worldwide. We have previously shown that Schistosoma mansoni soluble egg antigens (SEA) activate the proto-oncogene c-Jun in enterocytes. c-Jun belongs to the AP-1 transcription factor family. We aimed to investigate receptors, pathways, and gene regulation involved in AP-1 promotor activation.

Methods The promotor activity of AP-1 in SEA-stimulated SW620 cells was analyzed via luciferase AP-1 reporter gene assays. Insulin-like-growth-factor1-receptor (IGF1-R), insulin receptor (IR), and downstream kinases such as Akt 1/2/3 and ERK 1/2 were specifically inhibited under SEA incubation. Additionally, the effect of androgen receptor inhibition on AP-1-induction was investigated in the presence of SEA stimulation.

Results SEA stimulation induced a concentration-dependent AP-1 activity in the reporter gene assay. SEA induced activation of the AP-1 transcription factor was reduced by the inhibition of IGF1-R/IR (corr. sig. p=0,014) and the inhibition of the androgen receptor (corr. sig. p=0,030). Also the inhibition of downstream kinases Akt 1/2/3 and ERK 1/2 led to a decrease of AP-1 promotor activity (corr. sig. p=0,000). The inhibition of both receptors simultaneously potentiated this reduction.

Conclusion With our results we identified two receptors (androgen and insulin receptor) as well as downstream pathways (AP-1 activation), which are functionally activated by SEA in colon epithelial cells. These findings might be useful for new therapeutic approaches.

Publication History

Article published online:
26 January 2022