Abstract
The gingival epithelium is becoming known as a regulator of the oral innate immune responses to a variety of insults such as bacteria and chemicals, including those chemicals found in cigarette smoke. We investigated the effects of whole cigarette smoke on cell-surface-expressed Toll-like receptors (TLR)-2, −4 and −6, human β-defensin (HBD) and proinflammatory cytokine expression and production in primary human gingival epithelial cells. Whole cigarette smoke was shown to increase TLR2, TLR4 and TLR6 expression. Cigarette smoke led to ERK1/2, p38 and JNK phosphorylation in conjunction with nuclear factor-κB (NFκB) translocation into the nucleus. TLR expression following cigarette smoke exposure was down regulated by the use of ERK1/2, p38, JNK MAP kinases, and NFκB inhibitors, suggesting the involvement of these signaling pathways in the cellular response against cigarette smoke. Cigarette smoke also promoted HBD2, HBD3, IL-1β, and IL-6 expression through the ERK1/2 and NFκB pathways. Interestingly, the modulation of TLR, HBD, and cytokine expression was maintained long after the gingival epithelial cells were exposed to smoke. By promoting TLR, HBDs, and proinflammatory cytokine expression and production, cigarette smoke may contribute to innate immunity dysregulation, which may have a negative effect on human health.
Highlights
Tobacco smoking has been associated with an increased incidence of bacterial infections, chronic pulmonary obstructive disease (COPD), asthma and bronchitis [1,2,3]
Cell exposure for 15 or 30 min showed a significant (p,0.05) increase of TLR4 mRNA expression compared to that observed in the controls
Epithelial Cells Because the activation of Toll-like receptors (TLR) led to pro-inflammatory cytokine expression [42], and because we demonstrated that cigarette smoke stimulated the expression of these TLRs by gingival epithelial cells, we proceeded to examine IL-1b and IL-6 expression and secretion
Summary
Tobacco smoking has been associated with an increased incidence of bacterial infections, chronic pulmonary obstructive disease (COPD), asthma and bronchitis [1,2,3]. Smoking severely impairs several functions of both the alveolar macrophages and airway epithelial cells, including the inhibition of lipolysaccharide (LPS)induced expression of TNF-a, IL-1b, and IL-6 [10,11,12,13], microbicidal activity, and phagocytosis [14]. These observations suggest that smoking suppresses the ability of the host to develop the innate immune response to infection in the oral cavity [15,16]
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