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Published on: July 29, 2014
LL-37-dsRNA Complexes Modulate Immune Response via RIG-I in Oral Keratinocytes
Hiroki Kato1,2, Kouji Ohta3, Misaki Akagi1
1Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8553, Japan.
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.
Insights
The antimicrobial peptide LL-37 enhances inflammatory responses to nucleic acids in oral cells by interacting with double-stranded RNA and the RIG-I receptor. This interaction may contribute to oral inflammatory diseases.
Area of Science:
- Immunology
- Molecular Biology
- Oral Biology
Background:
- Nucleic acids act as danger signals (PAMPs/DAMPs), triggering inflammation.
- LL-37, an antimicrobial peptide, modulates immune responses, but its role in nucleic acid-induced inflammation in oral keratinocytes is unclear.
Discussion:
- LL-37 enhances CXCL10 expression induced by necrotic cell supernatant (NCS) in oral keratinocytes (RT7), an effect reduced by RNase.
- LL-37 forms complexes with double-stranded RNA (Poly(I:C)) that amplify CXCL10 expression and activate NF-κB.
- LL-37 facilitates the cytoplasmic translocation of dsRNA, promoting RIG-I-mediated immune responses.
Key Insights:
- LL-37 binds to dsRNA and enters the cytoplasm.
- RIG-I activation is crucial for the inflammatory response mediated by LL-37-dsRNA complexes.
- LL-37 modulates dsRNA-induced inflammation via RIG-I in oral keratinocytes.
Outlook:
- LL-37's role in RIG-I-mediated dsRNA responses suggests a potential mechanism in oral inflammatory diseases.
- Further research could explore therapeutic strategies targeting the LL-37-nucleic acid-RIG-I axis.
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