Actinobacillus actinomycetemcomitans‐induced expression of IL‐1α and IL‐1β in human gingival epithelial cells: role in IL‐8 expression

Abstract

Gingival epithelial cells (GEC) are the first cells of the host that encounter the periodontal pathogens. and therefore their role in the initiation of the inflammatory response is critical. We aimed to: 1) characterize the expression of interleukin (IL)- Ialpha and IL-Ibeta in human gingiva and cultured GEC: 2) demonstrate the ability of A. actinomycetemcomitans extracts to upregulate IL-1alpha, IL-1beta and IL-8 expression in GEC in vitro: and 3) characterize the role of IL-1alpha and IL-1beta in the induction of IL-8 expression in GEC in vitro. Ten gingival biopsies (5 inflamed and 5 controls) and cultured GEC were examined for IL-1alpha and IL-Ibeta using immunohistochemical techniques. GEC were also challenged with A. actinomycetemcomitans extracts or IL-1alpha, and secretion of IL-1 and IL-8 was determined by ELISA. In vivo, IL-lalpha and IL-1beta were localized in the gingival epithelium and the infiltrating leukocytes. In vitro, A. actinomycetemcomitans extracts induced a time-dependent expression of IL-1alpha, IL-1beta and IL-8 in GEC. IL-1 inhibitors did not affect A. actinomycetemcomitans-induced IL-8. although they inhibited IL-8 induced by IL-1alpha or IL-1beta. In conclusion, GEC are a major source of IL-1alpha and IL-1beta in the periodontium, which in turn induce additional inflammatory mediators such as IL-8. Therefore GEC can be a potential target for therapeutic intervention in the future.

Upregulation of Intercellular Adhesion Molecule 1 and Proinflammatory Cytokines by the Major Surface Proteins of Treponema maltophilum and Treponema lecithinolyticum , the Phylogenetic Group IV Oral Spirochetes Associated with Periodontitis and Endodontic Infections

“…This means that induction of ICAM-1 expression in the THP-1 cells was not mediated via IL-1␤. A. actinomycetemcomitans-induced IL-8 expression has also been reported to be not mediated by IL-1␤ (45).…”

“…It is believed to play an important role in initiating the inflammatory reactions in gingival tissues, and its level of expression is related to the severity of periodontitis. Stimulated IL-8 production in the inflamed gingiva has been reported in the epithelium (45,48), gingival fibroblasts (52), and monocytes (47). In addition, the level of IL-8 was significantly elevated in the GCF of periodontitis patients compared to the GCF of healthy subjects (16).…”

Gingival and dermal fibroblasts produce interleukin‐1β converting enzyme and interleukin‐1β but not interleukin‐18 even after stimulation with lipopolysaccharide

“…Lipopolysaccharides (LPS) from Gram-negative bacteria are powerful immunostimulatory agents that induce the production and release of many proinflammatory cytokines by immune cells (Dijkmans et al, 1990). Common oral flora bacteria such as Fusobacterium nucleatum, Eikenella corrodens, and Actinobacillus actinomycetemcomitans induce the production of cytokines in gingival epithelial cells (Han et al, 2000;Sfakianakis et al, 2001;Yumoto et al, 2001), while P. gingivalis alters cytokine production once it invades epithelial cells (Saito et al, 1996). In addition to epithelial cells, the possible role of gingival fibroblasts in host defenses should also be considered.…”

Oral microbe-host interactions: influence of β-glucans on gene expression of inflammatory cytokines and metabolome profile

“…In a study of experimental gingivitis, an increased concentration of IL-1 in gingival crevicular fluid was demonstrated [39]. The expression of IL-1-α and IL-1-β was induced in vitro from cultured gingival epithelial cells that were challenged with A. actinomicetemcomitans extracts [40]. These results indicate that gingival epithelial cells are the main source of these interleukins of the periodontium, which induce the production of additional inflammatory mediators [40].…”