Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami‑Ku, Hiroshima 734‑8553, Japan.
Department of Public Oral Health, Program of Oral Health Sciences, Hiroshima University, Minami‑Ku, Hiroshima 734‑8553, Japan.
Mol Med Rep. 2022 Mar;25(3). doi: 10.3892/mmr.2022.12622. Epub 2022 Feb 1.
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.
口腔固有免疫系统在宿主防御口腔黏膜病毒入侵中具有重要作用。多聚（ADP-核糖）聚合酶 13（PARP13）具有很强的抗病毒能力，据报道其具有两种同工型；全长蛋白锌指抗病毒蛋白长（ZAPL）和较短的蛋白（ZAPS）。然而，这两种同工型在口腔黏膜中的表达和功能尚不清楚。在本研究中，研究了转染双链 RNA（dsRNA）、Poly（I:C）和 dsDNA、Poly（dA:dT）诱导的 ZAPL 和 ZAPS 在永生化口腔角质形成细胞和成纤维细胞（RT7 和 GT1 细胞系）中的表达水平。随后，研究了敲低 ZAPL 和 ZAPS 对转染核苷酸诱导的抗病毒因子的影响。结果表明，ZAPL 和 ZAPS 在 RT7 和 GT1 细胞中持续表达，与未转染相比，Poly（I:C）和 Poly（dA:dT）转染后两种细胞类型的表达均显著增加。在 RT7 细胞中特异性敲低 ZAPL 和 ZAPS 可降低转染 Poly（I:C）和 Poly（dA:dT）诱导的 IFN-β 和 C-X-C 基序趋化因子配体 10（CXCL10）表达。另一方面，在 GT1 细胞中敲低 ZAPL 和 ZAPS 可降低转染核苷酸诱导的 CXCL10 表达，而对 Poly（dA:dT）诱导的 IFN-β 表达无影响。它们的敲低也与两种细胞类型中转染核苷酸诱导的 IFN 调节因子 3 磷酸化有关。综上所述，这些结果表明，PARP13 的同工型 ZAPL 和 ZAPS 参与了口腔黏膜细胞抵抗病毒感染的宿主防御。
