β1 Integrin/FAK signaling regulates interleukin-8 production in human gingival epithelial Ca9-22 cells

Abstract

Objectives

Interleukin-8 (IL-8), a proinflammatory factor in human tissues, plays an important role in inflammation. Type IV collagen, a key component of the basement membrane, interacts with integrins, which are primary receptors in the extracellular matrix (ECM). Integrins are essential for the regulation of various cellular behaviors and signal transduction pathways. However, the relationship between type IV collagen, β1 integrin, and gingival epithelial cells is poorly understood. The aim in this study was to elucidate the effect of the interaction between type IV collagen and β1 integrin on IL-8 secretion in human gingival epithelial cells (Ca9-22).

Methods

Ca9-22 cells were treated with or without type IV collagen, and IL-8 production was assessed using an enzyme-linked immunosorbent assay (ELISA). The role of β1 integrin was investigated using a β1 integrin-neutralizing antibody. Western blotting was performed to measure the phosphorylation levels of the relevant proteins. The effects of the focal adhesion kinase (FAK) inhibitor Y15 and the MEK inhibitor U0126 on β1 integrin/FAK and Erk1/2 MAPK pathways in IL-8 production were evaluated to explore the involvement of these signaling pathways.

Results

β1 integrin induced IL-8 secretion in the Ca9-22 cells by regulating FAK, Erk1/2, and p130Cas proteins. p130Cas was independent of FAK, whereas Erk1/2 functioned downstream of FAK. Inhibition of FAK or Erk1/2 substantially reduced IL-8 secretion, highlighting their pivotal roles in this signaling pathway.

Conclusion

β1 integrin promotes IL-8 secretion in Ca9-22 cells via the β1 integrin/FAK/Erk1/2 signaling pathway. These findings elucidate the pathogenesis of periodontitis and provide a foundation for the development of targeted therapeutic strategies.