Granulocyte chemotactic protein 2 (gcp-2/cxcl6) complements interleukin-8 in periodontal disease.
OBJECTIVE
Mucosal inflammatory responses are orchestrated largely by pro-inflammatory chemokines. The chemokine granulocyte chemotactic protein 2 (CXCL6) is involved in neutrophil recruitment and migration. Previous studies have shown that granulocyte chemotactic protein 2 is up-regulated during mucosal inflammation (e.g. in inflammatory bowel disease), similarly to the functionally and structurally related chemokine interleukin-8. Nevertheless, unlike interleukin-8, a role of granulocyte chemotactic protein 2 in gingival inflammation has not been yet demonstrated. In this study we aimed to evaluate the expression of the chemokine granulocyte chemotactic protein 2 in clinically healthy vs. diseased gingival tissues and to explore possible correlations with clinical and microbiological markers of periodontitis.


METHODS
Gene expression in 184 'diseased' and 63 'healthy' gingival tissue specimens from 90 patients with periodontitis was analyzed using Affymetrix U133Plus2.0 arrays. The expression of granulocyte chemotactic protein 2 was further confirmed by real-time reverse transcription-polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay, while the localization of granulocyte chemotactic protein 2 in gingival tissues was analyzed by immunohistochemistry. Plaque samples from the adjacent periodontal pockets were collected and evaluated for 11 species of periodontal bacteria using checkerboard DNA-DNA hybridizations.


RESULTS
Among all known chemokines, GCP-2 expression was the most up-regulated (3.8-fold, p < 1.1 x 10(-16)), in 'diseased' vs. 'healthy' tissue as compared to a 2.6-fold increased expression of interleukin-8 mRNA (p < 1.2 x 10(-15)). Increased expression of granulocyte chemotactic protein 2 correlated with higher levels of 'red' and 'orange' complex pathogens and with increased probing depth, but not with attachment loss. Immunohistochemistry showed that granulocyte chemotactic protein 2 was expressed in gingival vascular endothelium.


CONCLUSIONS
The level of expression of granulocyte chemotactic protein 2 correlates with the severity of periodontitis and appears to act as a hitherto unrecognized functional adjunct to interleukin-8 in diseased gingival tissues.
Kebschull
M
M
Division of Periodontics, Section of Oral and Diagnostic Sciences, College of Dental Medicine, Columbia University, New York, NY 10032, USA.
Demmer
R
R
Behle
J H
JH
Pollreisz
A
A
Heidemann
J
J
Belusko
P B
PB
Celenti
R
R
Pavlidis
P
P
Papapanou
P N
PN
D000190:Actinomyces / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000368:Aged; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology; D010520:Aggressive Periodontitis / Q000276:immunology* / Q000382:microbiology; D001439:Bacteroides / Q000276:immunology; D044883:Campylobacter rectus / Q000276:immunology; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000276:immunology*; D055113:Chronic Periodontitis / Q000276:immunology* / Q000382:microbiology; D003773:Dental Plaque / Q000382:microbiology; D016124:Eikenella corrodens / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology; D005260:Female; D016967:Fusobacterium nucleatum / Q000276:immunology; D005881:Gingiva / Q000098:blood supply / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017622:Periodontal Attachment Loss / Q000276:immunology / Q000382:microbiology; D010514:Periodontal Pocket / Q000276:immunology / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000276:immunology; D018713:Prevotella intermedia / Q000276:immunology; D051116:Receptors, Scavenger / Q000276:immunology*; D048373:Treponema denticola / Q000276:immunology; D015854:Up-Regulation; D014678:Veillonella / Q000276:immunology; D055815:Young Adult
C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D018836:Inflammation Mediators; D016209:Interleukin-8; D051116:Receptors, Scavenger