RESUMO
Histamine H1 receptor (H1R) gene is upregulated in patients with pollinosis; its expression level is highly correlated with the nasal symptom severity. Antihistamines are widely used as allergy treatments because they inhibit histamine signaling by blocking H1R or suppressing H1R signaling as inverse agonists. However, long-term treatment with antihistamines does not completely resolve toluene-2,4-diisocyanate (TDI)-induced nasal symptoms, although it can decrease H1R gene expression to the basal level, suggesting additional signaling is responsible for the pathogenesis of the allergic symptoms. Here, we show that treatment with suplatast tosilate in combination with antihistamines markedly alleviates nasal symptoms in TDI-sensitized rats. Suplatast suppressed TDI-induced upregulation of IL-9 gene expression. Suplatast also suppressed ionomycin/phorbol-12-myristate-13-acetate-induced upregulation of IL-2 gene expression in Jurkat cells, in which calcineurin (CN)/nuclear factor of activated T-cells (NFAT) signaling is known to be involved. Immunoblot analysis demonstrated that suplatast inhibited binding of NFAT to DNA. Furthermore, suplatast suppressed ionomycin-induced IL-9 mRNA upregulation in RBL-2H3 cells, in which CN/NFAT signaling is also involved. These data suggest that suplatast suppressed NFAT-mediated IL-9 gene expression in TDI-sensitized rats and this might be the underlying mechanism of the therapeutic effects of combined therapy of suplatast with antihistamine.
Assuntos
Antialérgicos/farmacologia , Sulfonatos de Arila/farmacologia , Antagonistas dos Receptores Histamínicos/farmacologia , Hipersensibilidade/tratamento farmacológico , Interleucina-9/genética , Fatores de Transcrição NFATC/genética , Doenças Nasais/tratamento farmacológico , Compostos de Sulfônio/farmacologia , Tolueno 2,4-Di-Isocianato/toxicidade , Animais , Antialérgicos/uso terapêutico , Sulfonatos de Arila/uso terapêutico , Calcineurina/fisiologia , Células Cultivadas , Quimioterapia Combinada , Expressão Gênica/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos/uso terapêutico , Hipersensibilidade/genética , Interleucina-9/metabolismo , Masculino , Fatores de Transcrição NFATC/fisiologia , Doenças Nasais/genética , Ratos , Receptores Histamínicos H1/genética , Receptores Histamínicos H1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Compostos de Sulfônio/uso terapêuticoRESUMO
We report the application of tapping-mode scanning probe electrospray ionization (t-SPESI) to mass spectrometry imaging of industrial materials. The t-SPESI parameters including tapping solvent composition, solvent flow rate, number of tapping at each spot, and step-size were optimized using a quadrupole mass spectrometer to improve mass spectrometry (MS) imaging of thin-layer chromatography (TLC) and additives in polymer films. Spatial resolution of approximately 100 µm was achieved by t-SPESI imaging mass spectrometry using a fused-silica capillary (50 µm i.d., 150 µm o.d.) with the flow rate set at 0.2 µL/min. This allowed us to obtain discriminable MS imaging profiles of three dyes separated by TLC and the additive stripe pattern of a PMMA model film depleted by UV irradiation.
