Human Gingival Tissue: a New Site of C-Reactive Protein Formation?

Background & aim: Emerging evidence shows that C-reactive protein (CRP) is a strong independent predictor of future cardiovascular events, and periodontal disease is associated with increased serum levels of CRP and IL-6 thereby contributing to systemic inflammation and increase of the risk for cardiovascular disease. CRP is primarily synthesized in liver, while it has been detected in saliva and gingival crevicular fluid. Currently it remains unknown whether gingival tissue per se is capable of producing CRP. This study aimed to investigate CRP expression in human gingiva. Methods: A total of 94 gingival biopsies were collected, including 76 samples from 44 patients with chronic periodontitis and 18 samples from 18 periodontally healthy subjects. CRP expression was detected by immunohistochemistry. The mRNA expression of CRP and IL-6 was examined by reverse transcriptase polymerase chain reaction (RT-PCR). CRP expression was also examined in reconstituted human gingival epithelia by particle-enhanced immunoturbidimetric assay and RT-PCR. Results: CRP was expressed in both gingival epithelia and the underlying connective tissues in periodontitis patients and healthy subjects. The detection frequency was 58.3% in the patients and 62.5% in the healthy subjects. The expression profile of CRP varied among the patients, while its expression pattern and level at the paired gingival tissues collected from unresolved periodontitis sites and the adjacent healthy sites were intercorrelated within a same subject. CRP mRNA was detected in all samples examined and its expression was positively correlated with IL-6 (r=0.694, p<0.001). Both protein and mRNA expressions of CRP were detected in the reconstituted human gingival epithelia. Conclusions: The present study for the first time shows that human gingiva is a new site of CRP formation. Further study is warranted to elaborate the clinical implications of the current findings. Supported by the Hong Kong Research Grants Council, HKU 7518/05M, and HKU CRCG to LJ.