Periodontitis is a chronic inflammatory condition caused by a host-bacteria interaction that is characterized by the loss of periodontal attachment [1]. Interleukin (IL)-1β, IL-6, IL-8, and cyclooxygenase (COX)-2 are produced when subgingival biofilm periodontopathogenic microorganisms, their byproducts, and products infiltrate immunoinflammatory and resident cells of the periodontium. This inflammatory response results in the breakdown of soft tissue and bone resorption [2], [3], [4], [5]. Although periodontal and inflammatory cells also produce anti-inflammatory cytokines such as IL-1 receptor antagonist and IL-10, these are not sufficient to prevent the excessive inflammatory response induced by pathogenic microbiota [6]. Thus, eliminating the pathogenic microbiota is fundamental in preventing and healing periodontitis [7]. Previously we demonstrated that Porphyromonas gingivalis (P. gingivalis) is a pathogenic microorganism that produces lipopolysaccharide (LPS) induced modifications in the phenotypic and inflammatory characteristics of human gingival fibroblasts (HGF) [8]. Cell proliferation was suppressed, and pro-inflammatory changes increased.

Boron in the form of boric acid (BA), borate, and the boroester fructoborate has been found to decrease markers of inflammatory stress such as increased C-reactive protein in humans [9], [10]. Animal models have shown that boric acid reduces periodontal inflammation and attachment loss, which supports the concept that it may be useful in the management of periodontitis [11], [12]. The bases for this concept are findings showing that boron-containing compounds have antimicrobial, anti-inflammatory, and immune-regulatory properties [13]. The findings indicate that boron regulates cytokine production such that beneficial but not harmful levels of reactive oxygen species occur [14]. Boron deprivation was found to reduce the expression of 30 of 31 inflammatory-associated cytokines and chemokines in mice six days after infection with Heligmosomoide bakeri [15]. This finding indicates that boron might help fight the infection. Most studies, however, indicating that boron may regulate cytokine action have found that it reduces cytokines that are elevated under conditions of inflammatory and oxidative stress. For example, a derivative of boric acid, AN0128, has been suggested to have anti-inflammatory and immune regulatory effects through preventing the release tumor necrosis factor (TNF) in periodontal disease [6], [11]. Cell culture studies have shown that boric acid inhibits lipopolysaccharide-induced TNF-α formation in human monocytic leukemia THP-1 cells and that calcium fructoborate reduces IL-1 and IL-6 release by lipopolysaccharide-stimulated murine macrophage RAW 264.7 cells [16]. Previously, we found that boric acid improved cell viability and increased the expressions of cytokines in human gingival fibroblasts with nicotine-induced inflammatory and oxidative stress [17]. We have also found in a clinical trial that a minimum concentration of boric acid (0.75 %), which is biocompatible to human gingival fibroblast/human periodontal ligament fibroblasts, inhibited gram-positive and gram-negative bacteria, including Streptococcus mutans, Staphylococcus aureus, Enterococcus faecium (vancomycin-resistant clinical isolate), Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa in periodontitis [18].

The objective of the present study was to determine whether boric acid could improve the pro-inflammatory and anti-inflammatory cytokines profile and antioxidant status in IL-1β induced inflammatory stressed human gingival fibroblasts.