benzofurans and Eosinophilia

Sulfuretin is one of the main flavonoids produced by Rhus verniciflua, which is reported to inhibit the inflammatory response by suppressing the NF-κB pathway. Because NF-κB activation plays a pivotal role in the pathogenesis of allergic airway inflammation, we here examined the effect of sulfuretin on an ovalbumin-induced airway inflammation model in mice. We isolated sulfuretin from R. verniciflua. Sulfuretin was delivered intraperitoneally after the last ovalbumin challenge. Airway hyper-responsiveness, cytokines, mucin, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. A single administration of sulfuretin reduced airway inflammatory cell recruitment and peribronchiolar inflammation and suppressed the production of various cytokines in bronchoalveolar fluid. In addition, sulfuretin suppressed mucin production and prevented the development of airway hyper-responsiveness. The protective effect of sulfuretin was mediated by the inhibition of the NF-κB signaling pathway. Our results suggest that sulfuretin may have therapeutic potential for the treatment of allergic airway inflammation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzofurans; Bronchoalveolar Lavage Fluid; Chemotaxis; Cytokines; Eosinophilia; Flavonoids; Male; Mice; Mice, Inbred BALB C; Mucins; NF-kappa B; Pneumonia; Respiratory Hypersensitivity

The synthesis and pharmacological profile of a novel series of 7-methoxybenzofuran-4-carboxamides is described. Some of these compounds were found to be potent inhibitors of phosphodiesterase type 4 (PDE4).

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Administration, Oral; Animals; Asthma; Benzamides; Benzofurans; Cyclic Nucleotide Phosphodiesterases, Type 4; Eosinophilia; Guinea Pigs; Inhibitory Concentration 50; Phosphodiesterase Inhibitors; Pyridines; Rolipram; Structure-Activity Relationship; Vomiting

Eotaxin, a selective chemoattractant for eosinophils, induces lung eosinophilia and bronchial hyperresponsiveness (BHR) when administered intratracheally to interleukin-5 (IL-5) transgenic mice. We determined whether these effects of eotaxin were mediated through the production of cysteinyl-leukotrienes. IL-5 transgenic mice were administered eotaxin (5 micrograms) intratracheally after pretreatment with either diluent or a selective 5-lipoxygenase inhibitor SB210661 or a cysteinyl-leukotriene receptor antagonist, pranlukast. Twenty-four hours later, bronchial responsiveness to acetylcholine was measured and the degree of eosinophil influx was determined in bronchoalveolar lavage fluid (BALF) or in lung tissue. Both pranlukast and SB210661 significantly attenuated BHR induced by eotaxin with logPC(50), which is the concentration of acetylcholine needed to increase baseline insufflation pressure by 50%, from -0.43 +/- 0.16 to 0.39 +/- 0.10 and from -0.22 +/- 0.10 to 0.53 +/- 0.10, respectively (p < 0.05). There was also a significant attenuation of the eosinophil counts in BALF and in airways. BALF levels of leukotriene C(4) (LTC(4)) showed a significant increase after eotaxin from 23.9 +/- 6.7 to 165.0 +/- 35.0 pg/ml (p < 0.05) but were partially suppressed by both SB210661 (71.2 +/- 21.0) and pranlukast (62.7 +/- 11.5). Concentrations of LTB(4) were not significantly changed. We conclude that eotaxin-induced effects in the airways of IL-5 transgenic mice are partly mediated by the activation of 5-lipoxygenase enzyme leading to the generation of cysteinyl-leukotrienes.

Topics: Acetylcholine; Airway Resistance; Animals; Benzofurans; Bronchial Hyperreactivity; Bronchial Provocation Tests; Chemokine CCL11; Chemokines, CC; Chemotactic Factors, Eosinophil; Chromones; Cysteine; Cytokines; Eosinophilia; Eosinophils; Interleukin-5; Leukocyte Count; Leukotriene Antagonists; Leukotrienes; Lipoxygenase Inhibitors; Mice; Mice, Inbred CBA; Mice, Transgenic; Urea