Nuclear IL-33 regulates cytokinesis and cell motility in normal human epidermal keratinocytes. Issue 2 (February 2022)

• Record Type: Journal Article
• Authors: Tsuda, Hidetoshi; Tominaga, Shin-ichi; Ohtsuki, Mamitaro; Komine, Mayumi
• Is Part Of: Journal of dermatological science. Volume 105:Issue 2(2022)
• Page Start: 113
• Page End: 120
• Publication Date: 2022-02
• Subjects: IL; interleukin -- Th; T helper -- NF-κB; nuclear factor kappa B -- NHEK; normal human epidermal keratinocytes -- KD; knock-down -- BrdU; bromodeoxyuridine -- MTT; 3–4, 5 dimethylthiazol-2, 5 diphenyl tetrazolium bromide -- si; small interference -- RhoA; Ras homolog gene family, member A -- GTP; Guanosine triphosphate -- GDP; Guanosine diphosphate -- LIMK; LIM domain kinase -- Rock; rho-associated, coiled-coil-containing protein kinase -- ECT2; Epithelial cell transforming sequence 2 -- MLC; myosin light chain; Interleukin-33 -- Cell proliferation -- Cell division -- Keratinocyte; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2022.01.006
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: IL-33 is well known as an alarmin and a Th2 cytokine, but is now known as a nuclear protein to have influence on cell proliferation and cell division. We have demonstrated in this study that IL-33 promote cell proliferation and cell division in cultured normal human epidermal keratinocytes. IL-33 knockdown resulted in decreased BrdU incorporation and increased number of G2/M phase cells and binucleated cells. Supplementation of IL-33 restored the decreased BrdU incorporation and increased number of G2/M phase cells. IL-33 knockdown affected cell division and motility by slightly decreasing RhoA activity through decreasing ECT2 expression. Abstract: 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.