Macrophage migration inhibitory factor regulates specific innate immune sensor responses in gingival epithelial cells

Abstract

Background:The gingival epithelium protects periodontal tissues and the alveolar bone by maintaining a steady state of regulated inflammatory surveillance, also known as healthy homeostasis. Accordingly, the repertoire of receptors present within the gingival epithelium showcases its ability to recognize microbial colonization and contribute to bacterial sensing. Macrophage migration inhibitory factor (MIF) is one of many cytokines that are expressed in this protective state and is involved in neutrophil regulation. However, its role in the maintenance of healthy gingival tissue has not been described. Methods: Gingival tissues from wild-type (WT) and Mif knock-out (KO) mice were stained for neutrophils and three key neutrophil chemoattractants: MIF, Gro-α/CXCL1, and Gro-β/CXCL2 in the junctional epithelium (JE). In addition, gene silencing studies were performed using gingival epithelial cells (GECs) to examine the role of MIF on transcription of key bacterial recognition receptors Toll-like receptors (TLR)-1, -2, -4, -6, -9 and interleukin-1 receptors (IL-1R1 and IL-1R2) in response to oral bacterial stimulation.Results: WT murine gingival tissues demonstrated high expression of MIF in the JE. In Mif KO mice, despite the significant reduction of Gro-α/CXCL1 and Gro-β/CXCL2, there was a slight increase in neutrophils. Gene silencing experiments showed that MIF down-regulated the mRNA expression of TLR4, IL-1R1, and IL-1R2 in GEC, in addition to decreasing secreted IL-8/CXCL8 in response to bacteria. Conclusions: MIF regulates the expression of TLR4, IL-1Rs, and IL-8/CXCL8, components that are all involved in maintaining oral health. Our data demonstrate that MIF is a significant contributor to the maintenance of healthy oral homeostasis.

Periodontitis exacerbation during pregnancy in mice: Role of macrophage migration inhibitory factor as a key inductor

“…The PT Mif-/-and PGPD Mif−/− groups did not develop clinical signs and preserved tissue continuity compared to the PT WT and PGPD WT groups. These observations were corroborated by a histometric analysis 44,45 and supported that the presence of MIF influences the exacerbation of PT during pregnancy. In particular, the loss of tissue from the PGPD WT and PT WT groups was similar, with no significant differences, although both showed tissue destruction, mainly on the palatal side, with a 31% greater loss than on the buccal side.…”

Evaluation of the Effects of E-Cigarette Aerosol Extracts and Tobacco Cigarette Smoke Extracts on Human Gingival Epithelial Cells

“… 18 The decreased survival rate of HGEs will destroy the homeostasis of oral microorganisms, leading to the accumulation of oral pathogenic microorganisms, the formation of dental plaque and the development of periodontitis. 38 From our results, a high concentration of CS and e-cigarettes both reduced cell survival. Thus, CS had a greater impact on cell survival which suggested that tobacco might be more likely to cause periodontitis than e-cigarettes.…”

“…HGEs play an important role in oral gingival tissue, being the first cells to be exposed to the environment, acting as a barrier against invading bacteria and acting as an antibacterial agent . The decreased survival rate of HGEs will destroy the homeostasis of oral microorganisms, leading to the accumulation of oral pathogenic microorganisms, the formation of dental plaque and the development of periodontitis . From our results, a high concentration of CS and e-cigarettes both reduced cell survival.…”