Stromal cell–derived factor-1–derived peptide S12 suppresses interleukin-1β–mediated inflammatory signaling in oral epithelial cells
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Inflammation is a fundamental host defense mechanism against external insults; however, excessive immune activation contributes to inflammatory diseases such as periodontitis, resulting in periodontal tissue destruction and tooth loss. Interleukin-1β (IL-1β), a key pro-inflammatory cytokine, stimulates oral epithelial cells to produce interleukin-8 (IL-8), which recruits neutrophils and amplifies local inflammation. Therefore, regulation of IL-1β–induced IL-8 secretion in oral epithelial cells is critical for controlling pathological inflammatory responses. Peptide-based therapeutics have attracted increasing interest due to their specificity and biocompatibility, highlighting their potential as anti-inflammatory agents. This study investigated the anti-inflammatory effects and mechanisms of a human stromal cell–derived factor-1 (SDF-1)–derived peptide in IL-1β–stimulated oral epithelial cells. Human oral epithelial KB cells and immortalized human oral keratinocytes were treated with IL-1β in the presence or absence of SDF-1–derived peptides. IL-8 secretion was measured by enzyme-linked immunosorbent assay, and activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was examined by western blotting. IL-1β significantly increased IL-8 secretion and induced phosphorylation of NF-κB p65 and MAPKs, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase, and p38. Inhibition of ERK and p38 markedly reduced IL-8 expression, indicating their central roles in IL-1β signaling. Among 18 SDF-1δ–derived peptides, S12 exerted the strongest inhibitory effect, reducing IL-8 secretion and suppressing IL-1β–induced NF-κB and MAPK phosphorylation. These results demonstrate that S12 attenuates IL-1β–driven IL-8 production by targeting key inflammatory signaling pathways, supporting its potential as a host-modulation therapeutic for periodontal disease.
Abstract
Inflammation is a fundamental host defense mechanism against external insults; however, excessive immune activation contributes to inflammatory diseases such as periodontitis, resulting in periodontal tissue destruction and tooth loss. Interleukin-1β (IL-1β), a key pro-inflammatory cytokine, stimulates oral epithelial cells to produce interleukin-8 (IL-8), which recruits neutrophils and amplifies local inflammation. Therefore, regulation of IL-1β–induced IL-8 secretion in oral epithelial cells is critical for controlling pathological inflammatory responses. Peptide-based therapeutics have attracted increasing interest due to their specificity and biocompatibility, highlighting their potential as anti-inflammatory agents. This study investigated the anti-inflammatory effects and mechanisms of a human stromal cell–derived factor-1 (SDF-1)–derived peptide in IL-1β–stimulated oral epithelial cells. Human oral epithelial KB cells and immortalized human oral keratinocytes were treated with IL-1β in the presence or absence of SDF-1–derived peptides. IL-8 secretion was measured by enzyme-linked immunosorbent assay, and activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was examined by western blotting. IL-1β significantly increased IL-8 secretion and induced phosphorylation of NF-κB p65 and MAPKs, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase, and p38. Inhibition of ERK and p38 markedly reduced IL-8 expression, indicating their central roles in IL-1β signaling. Among 18 SDF-1δ–derived peptides, S12 exerted the strongest inhibitory effect, reducing IL-8 secretion and suppressing IL-1β–induced NF-κB and MAPK phosphorylation. These results demonstrate that S12 attenuates IL-1β–driven IL-8 production by targeting key inflammatory signaling pathways, supporting its potential as a host-modulation therapeutic for periodontal disease.