[Early postoperative middle-ear ventilation -- risk for the transplant or guarantee for aeration of the tympanic cavity?]. / Frühe postoperative Paukeninsufflation -- Gefahr für das Transplantat oder Garant für ein Paukenlumen?

BACKGROUND: Sufficient ventilation of the tympanic cavity is a decisive factor for the success of the therapy and the prognosis after tympanoplastic surgery. With the postoperative use of the Valsalva- and Politzer-maneuver the patient is able to influence the aeration of the tympanic cavity in a positive way by autoinsufflation. However this implicates the risk of a dislocation of the transplant, which is possibly caused by high middle-ear pressure-peaks during the maneuvers mentioned. METHODS: The actual increase of pressure in the tympanic cavity respectively auditory canal during the Valsalva- and Politzer-maneuver is examined in 22 patients with chronic-mesotympanic Otitis media and additionally by using an experiment with a model of a reconstructed middle-ear. The risk of a transplant-dislocation after tympanoplasty type I is estimated. RESULTS: The increase of pressure in the middle ear respectively auditory canal -- and with that the possibility of a dislocation of the transplant -- is lower after Politzer- compared with Valsalva-maneuver. If the transplant is secured through silicon sheets and packings in the auditory canal, the probability of "blowing away" the newly created cover of the tympanon will be very small. CONCLUSIONS: Because of the benefits for the aeration of the tympanic cavity, an early post-operative insufflation of the middle-ear -- using the Politzer- and/or "cautious" Valsalva-maneuver -- is recommended.

The MAPK kinase kinase TAK1 plays a central role in coupling the interleukin-1 receptor to both transcriptional and RNA-targeted mechanisms of gene regulation.

Mechanisms of fulminant gene induction during an inflammatory response were investigated using expression of the chemoattractant cytokine interleukin-8 (IL-8) as a model. Recently we found that coordinate activation of NF-kappaB and c-Jun N-terminal protein kinase (JNK) is required for strong IL-8 transcription, whereas the p38 MAP kinase (MAPK) pathway stabilizes the IL-8 mRNA. It is unclear how these pathways are coupled to the receptor for IL-1, an important physiological inducer of IL-8. Expression of the MAP kinase kinase kinase (MAPKKK) TAK1 together with its coactivator TAB1 in HeLa cells activated all three pathways and was sufficient to induce IL-8 formation, NF-kappaB + JNK2-mediated transcription from a minimal IL-8 promoter, and p38 MAPK-mediated stabilization of a reporter mRNA containing IL-8-derived regulatory mRNA sequences. Expression of a kinase-inactive mutant of TAK1 largely blocked IL-1-induced transcription and mRNA stabilization, as well as formation of endogenous IL-8. Truncated TAB1, lacking the TAK1 binding domain, or a TAK1-derived peptide containing a TAK1 autoinhibitory domain were also efficient in inhibition. These data indicate that the previously described three-pathway model of IL-8 induction is operative in response to a physiological stimulus, IL-1, and that the MAPKKK TAK1 couples the IL-1 receptor to both transcriptional and RNA-targeted mechanisms mediated by the three pathways.

The NF-kappa b repressing factor is involved in basal repression and interleukin (IL)-1-induced activation of IL-8 transcription by binding to a conserved NF-kappa b-flanking sequence element.

Interleukin (IL)-8, a prototypic chemokine, is rapidly induced by the pro-inflammatory cytokine IL-1 but is barely detectable in noninduced cells. Although there is clear evidence that the transcription factor NF-kappaB plays a central role in inducible IL-8 transcription, very little is known about the cis-elements and trans-acting factors involved in silencing of the IL-8 promoter. By sequence comparison with the interferon-beta promoter, we found a negative regulatory element (NRE) in the IL-8 promoter overlapping partially with the NF-kappaB response element. Here we show that an NF-kappaB-repressing factor (NRF) binds to the IL-8 promoter NF-kappaB-NRE. Reduction of cellular NRF by expressing NRF antisense RNA results in spontaneous IL-8 gene expression. In contrast, IL-1-induced IL-8 secretion is strongly impaired by expressing NRF antisense RNA. Mutation of the NRE site results in loss of NRF binding and increased basal IL-8 transcription. On the other hand IL-1-induced IL-8 transcription is decreased by mutating the NRE. These data provide evidence for a dual role of the NRF in IL-8 transcription. Although in the absence of stimulation it is involved in transcriptional silencing, in IL-1-induced cells it is required for full induction of the IL-8 promoter.