Sphingosine-1-phosphate and its receptors have emerged as important modulators of the immune response. The sphingosine-1-phosphate prodrug 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol (FTY720) can alleviate experimental allergic airway inflammation. Nevertheless, the role of individual sphingosine-1-phosphate receptors in the regulation of allergic airway inflammation remains undefined. Using a newly characterized potent and selective sphingosine-1-phosphate receptor 1 (S1P 1 ) agonist with physical properties allowing airway delivery, we studied the contribution of S1P 1 signaling to eosinophilic airway inflammation induced in ovalbumin-immunized mice by airway challenges with ovalbumin. Airway delivery of receptornonselective sphingosine-1-phosphate prodrug significantly inhibits the sequential accumulation of antigen-presenting dendritic cells and CD4 ϩ T cells in draining lymph nodes. This in turn suppressed by Ͼ80% the accumulation of CD4 ϩ T cells and eosinophils in the airways. Systemic delivery of sphingosine-1-phosphate prodrug or of an S1P 1 -specific agonist at doses sufficient to induce lymphopenia did not inhibit eosinophil accumulation in the airways. In contrast, local airway delivery of S1P 1 -specific agonist inhibited airways release of endogenous CCL5 and CCL17 chemokines, and significantly suppressed accumulation of activated T cells and eosinophils in the lungs. Specific S1P 1 agonism in lungs contributes significantly to anti-inflammatory activities of sphingosine-1-phosphate therapeutics by suppressing chemokine release in the airways, and may be of clinical relevance.
Swallowing is a reflex that receives sensory information from the peripheral nerves and from the cerebral cortex. The aim of the present study was to investigate whether the sensory input from anterior teeth affects the functional characteristics of tongue pressure applied against the hard palate during swallowing. Subjects were eight healthy volunteers. Tongue pressure against the hard palate during swallowing 10 ml of water was measured under two conditions: preanesthesia and postanesthesia of anterior teeth. The sensory deprivation of anterior teeth was performed by periodontal anesthesia. Tongue pressure was measured using a multiple tactile array sensor (MTAS) with eight sensor channels arranged in tandem. The duration of the tongue pressure production during swallowing was increased under periodontal anesthesia. In addition, the maximum tongue pressure and the pressure integral during swallowing were decreased under periodontal anesthesia, in particular at the anterior region of the palate. These findings indicate that sensory input from anterior teeth, including periodontal mechanoreceptor, affects the deglutitive tongue pressure and duration and provides peripheral feedback to modulate some aspects of the neurophysiologic control of deglutitive tongue movement.
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