Predominant Expression of Chemokine GCP-2 (CXCL6) in Periodontitis Lesions

Objectives: The chemokine granulocyte chemoattractant protein 2 (GCP-2/CXCL6) is involved in neutrophil recruitment and migration. Previous studies showed that GCP-2 is upregulated in mucosal inflammation, e.g., in inflammatory bowel disease, similarly to the functionally and structurally related chemokine interleukin 8 (IL-8). Nevertheless, unlike IL-8, a role of GCP-2 in gingival inflammation has not yet been demonstrated. We aimed to evaluate the expression of GCP-2 in clinically healthy vs. diseased gingival tissues and to explore possible correlations with clinical, microbiological and immunological factors.

Methods: Gene expression in 184 diseased and 63 healthy gingival tissue specimens of 90 periodontitis patients was analyzed using Affymetrix U133Plus2.0 arrays. GCP-2 expression was further confirmed by real time RT-PCR, western blotting and ELISA while the localization of GCP-2 expression in the gingival tissues was analyzed by immuno-histochemistry. Plaque samples from the adjacent periodontal pockets were collected and evaluated for 19 periodontal species using checkerboard DNA-DNA hybridizations.

Results: Among all inflammatory chemokines, GCP-2 mRNA was the most expressed (3.8 fold, p<1.1x10^-16) in diseased vs. healthy tissue, as compared to a 2.6 fold increased expression of IL-8 mRNA (p<1.2x10^-15). Increased expression of GCP-2 correlated with higher levels of red and orange complex pathogens and with increased probing depth, but not with attachment loss. GCP-2 was found to be over-expressed in gingival vascular endothelium in diseased tissue samples.

Conclusion: GCP-2 is over-expressed in periodontitis, correlates with pocketing and levels of periodontal pathogens, and appears to act as a hitherto unrecognized functional adjunct to IL-8 in inflamed gingival tissues.

Supported by NIH grant DE015649 to PNP. MK was supported by a grant from Neue Gruppe Wissenschaftsfond, Germany.