Gingival crevicular fluid Bax, Bcl-xl, interleukin-22, and transforming growth factor beta 1 levels in stage III periodontitis

Abstract

Background: Intrinsic apoptosis plays a critical role in immune defense and inflammation. Its dysregulation is involved in various chronic diseases. The B-cell lymphoma 2 (Bcl-2) family primarily mediates this mitochondrial pathway. This study aimed to investigate the proapoptotic Bcl-2-associated X protein (Bax) and antiapoptotic B-cell lymphoma-extra large (Bcl-xl) levels and their association with interleukin-22 (IL-22) and transforming growth factor beta 1 (TGF-β1) in the gingival crevicular fluid (GCF) of patients with periodontitis.

Methods: A total of 75 systemically healthy nonsmokers were enrolled, of whom 23 had stage III periodontitis, 26 had gingivitis, and 26 were periodontally healthy. Whole-mouth clinical periodontal measurements were recorded. Bax, Bcl-xl, IL-22, and TGF-β1 levels in the GCF were determined by enzyme-linked immunosorbent assay (ELISA). Data were analyzed using nonparametric statistical tests.

Results: The periodontitis group had significantly lower GCF Bax levels than the gingivitis group (p < 0.05). The periodontitis and gingivitis groups had higher GCF Bcl-xl levels than the periodontally healthy group (p < 0.05). GCF IL-22 levels were similar in all groups (p > 0.05). The periodontitis group had lower GCF TGF-β1 levels than the gingivitis and periodontally healthy groups (p < 0.05). The diseased groups had a lower GCF Bax/Bcl-xl ratio than the healthy controls (p < 0.05). IL-22 was positively correlated with Bax (p < 0.05).

Conclusions: This is the first study investigating GCF Bax and Bcl-xl levels in periodontal health and disease. Increased GCF Bcl-xl levels and a decreased Bax/Bcl-xl ratio in stage III periodontitis implicate that those apoptotic proteins may be involved in the pathogenesis of periodontal disease. Further studies are needed to enlighten the possible role of Bax and Bcl-xl and their association with IL-22 and TGF-β1 in periodontal diseases.

Plain language summary: A type of cell death called intrinsic apoptosis plays an important role in the body's defense system, and its dysregulation is linked to different human diseases. The B-cell lymphoma 2-associated X protein (Bax) and B-cell lymphoma-extra large (Bcl-xl) are apoptosis-related proteins, which promote and inhibit cell death, respectively. This study aimed to investigate Bax and Bcl-xl levels and their association with the signaling proteins interleukin-22 (IL-22) and transforming growth factor beta 1 (TGF-β1) in the gingival crevicular fluid (GCF), which accumulates around the necks of the teeth of patients suffering from gum diseases such as gingivitis and periodontitis. Clinical parameters were recorded and GCF was collected. Bax, Bcl-xl, IL-22, and TGF-β1 levels were measured by biochemical assay in periodontally healthy individuals who had healthy gums (n = 26) and patients with periodontitis (n = 23) and gingivitis (n = 26). Periodontitis patients had lower Bax levels than gingivitis patients. Periodontitis and gingivitis patients had higher Bcl-xl levels and a lower Bax/Bcl-xl ratio than periodontally healthy individuals. IL-22 was positively correlated with Bax. The present findings suggest that the apoptotic regulatory molecules may be involved in the development of gum diseases, highlighting the need for further research in this area.

Keywords: apoptosis; cytokine(s); gingival crevicular fluid; gingivitis; periodontitis.