Kandilci, A. | bioRxiv Science

bioRxiv2023

NETosis Induced by Serum of Patients with COVID-19 is Reduced with Reparixin or Antibodies Against DEK and IL-8

DEK locates in the nucleus of the cells or the cytoplasmic granules of neutrophils and plays different roles in cellular processes including NETosis, a suicide mechanism of neutrophils. Here we showed that the interaction of rDEK with CXCR2 leads to NETosis, which could be reduced by the CXCR1/CXCR2 inhibitor reparixin. We found that IL-8, IL-6, IL1-{beta}, MPO, and CitH3 were increased whereas DEK was decreased in the serum of COVID-19 patients. Interestingly, reparixin or anti-DEK antibody reduced the NETosis induced by the serums of patients, suggesting that initial cytokine stimulation may further induce the release of DEK. Our results support the use of reparixin as a potential therapeutic strategy in COVID-19 and suggest that DEK-CXCR2 interaction plays a role in NETosis.

immunology↗

bioRxiv2022

Doxorubicin induces prolonged DNA damage signal in cells overexpressing DEK isoform-2.

DEK has a short isoform (DEK isoform-2; DEK2) that lacks amino acid residues between 49-82. The full-length DEK (DEK isoform-1; DEK1) is ubiquitously expressed and plays a role in different cellular processes but whether DEK2 is involved in these processes remains elusive. We stably overexpressed DEK2 in human bone marrow stromal cell line HS-27A, in which endogenous DEKs were intact or suppressed via short hairpin RNA (sh-RNA). We have found that contrary to ectopic DEK1, DEK2 locates in the nucleus and nucleolus, causes persistent {gamma}H2AX signal upon doxorubicin treatment, and couldnt functionally compensate for the loss of DEK1. In addition, DEK2 overexpressing cells were more sensitive to doxorubicin than DEK1-cells. Expressions of DEK1 and DEK2 in cell lines and primary tumors exhibit tissue specificity. DEK1 is upregulated in cancers of the colon, liver, and lung compared to normal tissues while both DEK1 and DEK2 are downregulated in subsets of kidney, prostate, and thyroid carcinomas. Interestingly, only DEK2 was downregulated in a subset of breast tumors suggesting that DEK2 can be modulated differently than DEK1 in specific cancers. In summary, our findings show distinct expression patterns and subcellular location and suggest non-overlapping functions between the two DEK isoforms.

cell biology↗