Localization of the chemokine interleukin‐8 and interleukin‐8 receptors in human gingiva and cultured gingival keratinocytes

Abstract

Interleukin-8 (IL-8) has been implicated in a wide variety of diseases. Previous studies have demonstrated the expression of IL-8 in periodontal tissues, yet little is known about the exact source(s), mechanisms and factors involved in gingival expression of IL-8. Additionally, nothing is known about the presence and distribution of IL-8 receptors (IL-8R) in gingival cells. Therefore it was hypothesized that, in vivo, periodontal pathogens induce IL-8 expression from gingival keratinocytes (GK) which enhances leukocyte, microvascular endothelial cell (MVEC) and GK migration via specific IL-8 receptors present on these cells. The objective of the present study was to determine the distribution of IL-8 and IL-8R in gingival tissues and cultured human GK in vitro. Standard immunohistochemical and immunocytochemical techniques were utilized in order to localize IL-8 and its receptors CXCR-1 and CXCR-2 in archival gingival specimens (eight periodontitis and four non-inflamed controls) and in cultured gingival keratinocytes. It was demonstrated that, in vivo, IL-8 and IL-8R were present in gingival epithelium, MVEC and leukocytes. In vitro studies verified the above results, by showing expression of IL-8 and IL-8R in cultured gingival keratinocytes. It is concluded that IL-8 and IL-8 receptors are expressed in gingival epithelium both in vivo and in vitro. This new evidence indicates that epithelium plays a critical role in the host defense against invading pathogens and that keratinocytes can actively respond to IL-8 and other host cytokines, via specific receptors.

Association between interleukin-8 levels and chronic periodontal disease

“…However, the results of the immunohistochemistry studies were inconsistent. Two of these studies [24,28] reported higher levels of IL-8 in individuals with periodontal disease and only 1 [27] study found higher levels of IL-8 in healthy tissues. The remaining 2 studies only evaluated the IL-8 presence in healthy or diseased gingival tissue, without comparing the IL-8 levels between individuals with and without CP.…”

Enhanced Expression of Interleukin-8 and Activation of Nuclear Factor Kappa-B in Endoscopy-negative Gastroesophageal Reflux Disease

“…Recent studies showing that IL-8 exerts mitogenic actions directly or by binding to its receptors on epithelial cells (31,32) lend support to our results. It is possible that IL-8, together with other cytokines and growth factors (25,33), could contribute to epithelial cell proliferation even in the early stage of endoscopy-negative GERD, and could be eventually linked to carcinogenesis.…”

Impact of endoscopically minimal involvement on IL-8 mRNA expression in esophageal mucosa of patients with non-erosive reflux disease

“…IL-8 also exerted mitogenic actions directly or by binding to its receptors on epithelial cells [20,21] . Taken together, it is possible that IL-8, together with other cytokines as well as growth factors [14,22] , could contribute to epithelial cell proliferation even in NERD, and could be eventually linked to carcinogenesis. Again, unlike CXCR-1, CXCR-2 is not specific for IL-8 and can bind to other chemokines such as growth related oncogene α, but it has 2-to 5-fold higher affinity for IL-8 than CXCR-1 [19] .…”