Nuclear IL-33 regulates cytokinesis and cell motility in normal human epidermal keratinocytes

Background: IL-33 is a dual-functional molecule; it acts as a cytokine to enhance type 2 inflammation, and as a nuclear factor. The roles of nuclear IL-33 are not yet fully understood.

Objective: We aimed to investigate the role of IL-33 in normal human epidermal keratinocytes (NHEKs).

Methods: We utilized RNA interference to knock down cellular IL-33.

Results: The IL-33-knockdown (KD) cells showed decreased BrdU incorporation and decreasing tendency in RhoA activity and decreased ECT2 oncogene expression, compared to the controls. Supplementation of IL-33 expression utilizing adenovirus vector recovered the BrdU incorporation in IL-33-KD cells. Increased number of G2/M phase cells and binucleated cells were observed among the KD cells. Overtime observation revealed that IL-33-KD cells could not divide properly, formed binucleated cells, and were less motile than control cells.

Conclusion: IL-33 KD in NHEKs affected the division and motility, probably by slightly decreasing the RhoA activity by attenuating ECT2 expression.