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LL-37-dsRNA Complexes Modulate Immune Response via RIG-I in Oral Keratinocytes

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Abstract

Recognition of nucleic acids as pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) promotes an inflammatory response. On the other hand, LL-37, an antimicrobial peptide, is a multifunctional modulator of immune response, though whether it modulates inflammatory responses induced by nucleic acids in oral keratinocytes is unknown. In this study, we firstly investigated the effect of LL-37 on CXCL10 induced by DAMPs and PAMPs in immortalized oral keratinocytes, RT7. Furthermore, the effects of LL-37 on translocation of exogenous nucleic acids into cytoplasm as well as cytosolic receptor, RIG-I on immune responses mediated by LL-37-nucleic acid complexes were examined. From these results, LL-37 enhanced necrotic cell supernatant (NCS)–induced CXCL10 expression in RT7, while the response was decreased by RNase. Complexes of LL-37 and double-stranded (ds) RNA, Poly(I:C) enhanced CXCL10 expression in comparison with each alone, which were associated with NF-κB activation. Furthermore, LL-37 was shown to bind with ds nucleotides and translocate into cytoplasm. Knockdown of RIG-I decreased expression of CXCL10 induced by LL-37-Poly(I:C) complexes, and RIG-I were co-localized with Poly(I:C) entered by LL-37 in cytoplasm. LL-37 modulates dsRNA-mediated inflammatory response via RIG-I in oral keratinocytes, which may play an important role in the pathogenesis of oral inflammatory diseases.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8553, Japan

    Hiroki Kato, Misaki Akagi, Shohei Fukada, Miyuki Sakuma, Takako Naruse & Tomonao Aikawa

  2. Department of Public Oral Health, Program of Oral Health Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8553, Japan

    Kouji Ohta & Hideo Shigeishi

  3. Department of General Dentistry, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8553, Japan

    Hiromi Nishi

  4. Department of Dentistry, Oral and Maxillofacial Surgery, National Hospital Organization Kure Medical Centerand, Chugoku Cancer Center , 3-1 Aoyama-Cho, Kure, 737-0023, Japan

    Hiroki Kato & Masaaki Takechi

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  1. Hiroki Kato
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  2. Kouji Ohta
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This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 17K11840).

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Correspondence to Kouji Ohta.

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Kato, H., Ohta, K., Akagi, M. et al. LL-37-dsRNA Complexes Modulate Immune Response via RIG-I in Oral Keratinocytes. Inflammation 46, 808–823 (2023). https://doi.org/10.1007/s10753-023-01787-5

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