• A Novel Method for the Treatment of Dentinal Hypersensitivity: Penetration of Magnetic Nanoparticles into Dentinal Tubules

      Kim, Se Jong; Masri, Radi, 1975- (2016)
      Dentinal hypersensitivity (DH) is characterized by temporary, sharp-shooting pain arising from exposed dentin in response to different types of stimuli, such as thermal, mechanical, osmotic or chemical elements This study looked the treatment of dentinal hypersensitivity (DH) by utilizing magnetic nanoparticles (MNPs). DH was simulated by creating a class V preparation on an extracted human tooth. 72 samples were divided into two groups. Three different MNPs (100nm, 300nm, 500nm) were applied to the class V preparation. A magnet was placed on the opposing side of the class V preparation for the experimental group. No magnet was used for the control group. All samples were decalcified, sectioned and mounted for visualization of MNPs through light and fluorescent microscopes. The percentage of dentinal tubule penetration of the three different MNP groups was calculated by measuring the total depth of the dentinal tubule from the inner surface of the preparation to the pulp. The second measurement was from the inner surface of the preparation to the depth that the MNPs travelled. Data were analyzed using ANOVA and Tukey's Honestly Significant Difference test. Overall, Smaller magnetic nanoparticles have a significantly higher percentage of dentinal tubule penetration than the larger magnetic nanoparticles with or without an external magnetic field (p≤.0005). There was no significant difference between the percentage of dentinal tubule penetration of 300nm and 500nm in control group. A significantly higher percentage of dentinal tubule penetration was found with application of the external magnetic field (p≤.0005). In conclusion, MNPs could potentially be utilized for DH treatment.
    • The role of STAT6 modulation of natural and inducible Tregs during Allergic Lung Inflammation

      Dorsey, Nicolas; Keegan, Achsah D. (2013)
      IL-4 plays a central role in allergic responses by activating the STAT6 pathway. Several studies indicate that regulatory T-cells (Treg) are modulated by IL-4 in vitro. We previously showed that STAT6-/- mice are highly resistant to allergic lung inflammation even when wild type Th2 effectors were provided and that they have increased numbers of Tregs. However, the role of STAT6 in modulating Tregs in vivo during allergic lung inflammation has not been thoroughly investigated. We hypothesized that IL-4-induced activation of STAT6 suppresses natural and inducible Treg differentiation, leading to enhanced allergic lung inflammation. Using a GFP marker for Tregs, we found that STAT6-/- mice have increased frequencies and total numbers of natural (n) Tregs in vivo and also increased frequencies of in vitro generated iTregs compared to STAT6-sufficient mice. Additionally, utilization of Helios and Nrp1 as markers for nTregs revealed a similar result. Taken together, these results suggest that STAT6-/- mice are highly resistant to Th2-driven inflammation because of their elevated numbers of Tregs. To test this hypothesis, STAT6-/-, STAT6xRAG2-/- and RAG2-/- mice were subjected to OVA-sensitization and challenge following adoptive transfer of OVA-specific, wild type Th2 effectors with or without prior Treg depletion/ inactivation using anti-CD25 (PC61). As expected, STAT6-/- mice were highly resistant to airway inflammation and remodeling. In contrast, allergic lung inflammation was partially restored in STAT6-/- mice treated with PC61 to levels observed in STAT6xRAG2-/- mice. In some cases, STAT6xRAG2-/- mice were also given nTregs along with Th2 effectors. Adoptive transfer of nTregs caused a substantial reduction in BAL eosinophil composition and suppressed airway remodeling and T-cell migration into the lung in STAT6xRAG2-/- mice to levels comparable to those in STAT6-/- mice. We also analyzed the contribution of another IL-4-activated signaling mediator, insulin receptor substrate 2 (IRS2). In contrast to STAT6, IRS2 suppressed iTreg expansion, but not nTreg expansion in vivo. These results illustrate that two signaling pathways activated by IL-4, STAT6 and IRS2, differentially antagonize Tregs in vivo. STAT6 and IRS2 both suppress iTregs, while only STAT6 suppresses nTregs. Furthermore, we demonstrate that STAT6 suppresses Tregs in vivo thereby promoting allergic airway inflammation.