Distinct Mechanisms for Induction and Tolerance Regulate the Immediate Early Genes Encoding Interleukin 1β and Tumor Necrosis Factor α

Interleukin-1β and Tumor Necrosis Factor α play related, but distinct, roles in immunity and disease. Our study revealed major mechanistic distinctions in the Toll-like receptor (TLR) signaling-dependent induction for the rapidly expressed genes (IL1B and TNF) coding for these two cytokines. Prior to induction, TNF exhibited pre-bound TATA Binding Protein (TBP) and paused RNA Polymerase II (Pol II), hallmarks of poised immediate-early (IE) genes. In contrast, unstimulated IL1B displayed very low levels of both TBP and paused Pol II, requiring the lineage-specific Spi-1/PU.1 (Spi1) transcription factor as an anchor for induction-dependent interaction with two TLR-activated transcription factors, C/EBPβ and NF-κB. Activation and DNA binding of these two pre-expressed factors resulted in de novo recruitment of TBP and Pol II to IL1B in concert with a permissive state for elongation mediated by the recruitment of elongation factor P-TEFb. This Spi1-dependent mechanism for IL1B transcription, which is unique for a rapidly-induced/poised IE gene, was more dependent upon P-TEFb than was the case for the TNF gene. Furthermore, the dependence on phosphoinositide 3-kinase for P-TEFb recruitment to IL1B paralleled a greater sensitivity to the metabolic state of the cell and a lower sensitivity to the phenomenon of endotoxin tolerance than was evident for TNF. Such differences in induction mechanisms argue against the prevailing paradigm that all IE genes possess paused Pol II and may further delineate the specific roles played by each of these rapidly expressed immune modulators. © 2013 Adamik et al

Mini-implants in the palatal slope – a retrospective analysis of implant survival and tissue reaction

<p>Abstract</p> <p>Background</p> <p>To identify insertion procedure and force application related complications in Jet Screw (JS) type mini-implants when inserted in the palatal slope.</p> <p>Methods</p> <p>Setting and Sample Population: The Department of Orthodontics, the University Hospital Münster. Forty-one consecutively started patients treated using mini-implants in the palatal slope. In this retrospective study, 66 JS were evaluated. Patient records were used to obtain data on the mode of utilization and complications. Standardized photographs overlayed with a virtual grid served to test the hypothesis that deviations from the recommended insertion site or the type of mechanics applied might be related to complications regarding bleeding, gingival overgrowth or implant failure.</p> <p>Results</p> <p>Two implants (3%) were lost, and two implants (3%), both loaded with a laterally directed force, exhibited loosening while still serving for anchorage. Complications that required treatment did not occur, the most severe problem observed being gingival proliferation which was attributable neither to patients’ age nor to applied mechanics or deviations from the ideal implant position.</p> <p>Conclusions</p> <p>The JS mini-implant is reliable for sagittal and vertical movements or anchorage purposes. Laterally directed forces might be unfavorable. The selection of implant length as well as the insertion procedure should account for the possibility of gingival overgrowth.</p