Key result
PARP13 knockdown reduces nucleotide-induced IFN-β and CXCL10 expression via IRF3 activation in oral mucosal cells.
Why the study?
The expression and function of the two PARP13 isoforms, ZAPL and ZAPS, in oral mucosa were unknown.
ZAPL and ZAPS isoforms of PARP13 are constitutively expressed in oral mucosal cells and participate in the host innate immune defense against viral infection by regulating antiviral factors.
Answers are grounded in this paper and cite their sources.
PARP13 isoforms may support mucosal antiviral responses; hypothesis-generating for human innate immunity, with no clinical implications yet.
Innate immune systems in the oral cavity have important roles in the host defense against viral invasion of oral mucosa. Poly(ADP‑ribose) polymerase 13 (PARP13), which has a strong antiviral ability, has been reported to possess two isoforms; a full‑length protein, zinc‑finger antiviral protein long (ZAPL), and a shorter protein (ZAPS). However, the expression and function of these two isoforms in oral mucosa remain unknown. In the present study, the expression levels of ZAPL and ZAPS induced by transfected double‑stranded (ds) RNA, Poly(I:C), and dsDNA, Poly(dA:dT), in immortalized oral keratinocytes and fibroblasts (RT7 and GT1 cell lines, respectively) were investigated. Subsequently, the effects of the knockdown of ZAPL and ZAPS on transfected nucleotide‑induced antiviral factors were examined. The results demonstrated constitutive expression of ZAPL and ZAPS in RT7 and GT1 cells, and their expression in both cell types was notably increased by transfection of Poly(I:C) and Poly(dA:dT) when compared with no transfection. Specific knockdown of ZAPL and ZAPS in RT7 cells decreased IFN‑β and C‑X‑C motif chemokine ligand 10 (CXCL10) expression induced by transfected Poly(I:C) and Poly(dA:dT). On the other hand, knockdown of ZAPL and ZAPS in GT1 cells decreased the expression of CXCL10 induced by the transfected nucleotides, whereas that had no effect on IFN‑β expression induced by Poly(dA:dT). Their knockdown was also associated with transfected nucleotides‑induced IFN regulatory factor 3 phosphorylation in both cell types. Taken together, these results indicate that ZAPL and ZAPS, isoforms of PARP13, in oral mucosal cells participate in host defense against viral infection of oral mucosa.
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Kato et al. (2022) studied this question. Knockdown of ZAPL and ZAPS vs. Control siRNA was evaluated on Expression of antiviral factors (IFN-β and CXCL10) and IRF3 activation. Knockdown of PARP13 isoforms ZAPL and ZAPS in oral mucosal cells decreased transfected nucleotide-induced expression of antiviral factors IFN-β and CXCL10 via IRF3 activation.
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