| Autor: |
Shunsuke, Miura, Sandra, Garcet, Xuan, Li, Inna, Cueto, Charissa, Salud-Gnilo, Norma, Kunjravia, Kazuhiko, Yamamura, Juana, Gonzalez, Mika, Murai-Yamamura, Darshna, Rambhia, James G, Krueger |
| Rok vydání: |
2022 |
| Zdroj: |
The Journal of investigative dermatology. |
| ISSN: |
1523-1747 |
| Popis: |
LL37 is produced by skin injury and bacterial infection and plays an important role in the early stages of psoriasis. In particular, the intracellular receptors TLRs 3, 7, 8, and 9 are thought to be involved in the pathogenesis of psoriasis in conjunction with LL37, but the interaction between TLR7/8 and LL37 in keratinocytes remains unclear. This study aimed to clarify the relationship between LL37 and TLR7/8 in keratinocytes and their involvement in the pathogenetic pathways seen in psoriasis using cultured keratinocytes and psoriasis patient skin samples. TLR7/8 was induced by LL37 in keratinocytes. TLR8 but not TLR7 functionally induced many psoriasis-related molecules, whereas IL-17C was not altered by the blockade of TLR7/8. While co-stimulated of LL37 with self-RNA/DNA did not show any interaction, LL37 itself would promote psoriasis-related genes. IL-36 receptor antagonistic antibody suppressed IL-17C induced by LL37. In psoriatic epidermis, LL37, TLRs, IL-17C, and IL-36γ expressions were increased and co-expressed with each other. Thus, we concluded that LL37 activates TLR8 in keratinocytes and induces IL-17C via induction of IL-36γ. Regulation of TLR8 or LL37 in keratinocytes could be a potential therapeutic strategy for psoriatic inflammation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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