P2X7 Receptor Indirectly Regulates the JAM-A Protein Content via Modulation of GSK-3ß.

The alveolar epithelial cells represent an important part of the alveolar barrier, which is maintained by tight junction proteins, particularly JAM-A, occludin, and claudin-18, which regulate paracellular permeability. In this study, we report on a strong increase in epithelial JAM-A expression in P2X7 receptor knockout mice when compared to the wildtype. Precision-cut lung slices of wildtype and knockout lungs and immortal epithelial lung E10 cells were treated with bleomycin, the P2X7 receptor inhibitor oxATP, and the agonist BzATP, respectively, to evaluate early changes in JAM-A expression. Biochemical and immunohistochemical data showed evidence for P2X7 receptor-dependent JAM-A expression in vitro. Inhibition of the P2X7 receptor using oxATP increased JAM-A, whereas activation of the receptor decreased the JAM-A protein level. In order to examine the role of GSK-3ß in the expression of JAM-A in alveolar epithelial cells, we used lithium chloride for GSK-3ß inhibiting experiments, which showed a modulating effect on bleomycin-induced alterations in JAM-A levels. Our data suggest that an increased constitutive JAM-A protein level in P2X7 receptor knockout mice may have a protective effect against bleomycin-induced lung injury. Bleomycin-treated precision-cut lung slices from P2X7 receptor knockout mice responded with a lower increase in mRNA expression of JAM-A than bleomycin-treated precision-cut lung slices from wildtype mice.

Odor deprivation influences human olfactory function.

Odor deprivation leads to anatomical and neurochemical changes in the olfactory system, but its effect on human olfaction has not been systematically explored. The present randomized, controlled study aimed to investigate whether odor deprivation by different methods can affect olfactory function in humans. In the present study, sixty-one healthy participants were randomly assigned into three groups: a nasal device group (wearing an intranasal silicone air diversion system for 6-8 h daily), a mask group (wearing a filtering face piece for 6-8 h daily) and a control group (no special instructions in terms of wearing masks). Before and immediately after a 14-day study phase, all participants underwent assessments of olfactory function, nasal patency and well-being. Following the 2-week observation period, the nasal device group exhibited significantly reduced TDI scores (with especially pronounced reductions for odor threshold scores), and the mask group exhibited a minor increase in odor identification scores compared with the control group. The change in well-being scores was positively associated with changes in odor identification and TDI scores. Olfactory deprivation using an intranasal silicone air diversion device is associated with olfactory impairment (especially for odor thresholds). Highlighting the exposure-driven plasticity of the olfactory system, it may serve as a possible model of hyposmia in future studies. In addition, it may also prove useful in patients with parosmia, possibly reducing the burden of unpleasant odorous sensations.