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. Peptidebased 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.

Cyclosporin A (CsA) plays an important role in clinical medicine and basic biology as an immunosuppressant and a mitochondrial permeability blocker, respectively. It was reported that CsA has a protective role by preventing apoptosis and promoting the proliferation in severed neurons. However, the molecular mechanisms for CsA-induced neuronal cell proliferation are unclear. In this study, we examined the mechanisms underlying the CsA-induced proliferation of PC12 cells. CsA increased the viability of PC12 cells in a dose(over 0.1~10 μM)-and time-dependent manner. The level of ROS generation was decreased in the CsA-treated PC12 cells. Expression of Bcl-2, an antiapoptotic molecule that inhibits the release of cytochrome c from the mitochondria into the cytosol, was upregulated, whereas Bax, a proapototic molecule, was not changed in the CsA-treated PC12 cells. CsA downregulated the mRNA expression of VDAC 1 and VDAC 3, but VDAC 2 was not changed in the CsA-treated PC12 cells. The level of cytosolic cytochrome c released from the mitochondria and the caspase-3 activity were attenuated in the CsA-treated PC12 cells. These results suggest that the mitochondria-mediated apoptotic signal and Bcl-2 family may play an important role in CsA-induced proliferation in PC12 cells.