Benzoxazole derivatives suppress lipopolysaccharide-induced mast cell activation

Abstract

Mast cells are central regulators of allergic inflammation that function by releasing various proallergic inflammatory mediators, including histamine, eicosanoids and proinflammatory cytokines. Occasionally, bacterial infections may initiate or worsen allergic inflammation. A number of studies have indicated that activation of lipoxygenase in mast cells positive regulates allergic inflammatory responses by generating leukotrienes and proinflammatory cytokines. In the present study, the effects of benzoxazole derivatives on the lipopolysaccharide (LPS)‑induced expression of proinflammatory cytokines, production of histamine and surface expression of co‑stimulatory molecules on bone marrow-derived mast cells (BMMCs) were studied. The benzoxazole derivatives significantly reduced the expression of interleukin (IL)‑1β, IL‑6, IL‑13, tumor necrosis factor‑α, perilipin (PLIN) 2, and PLIN3 in BMMCs treated with LPS. Furthermore, histamine production was suppressed in BMMCs treated with LPS, or treated with phorbol-12-myristate-13-acetate/ionomycin. Benzoxazole derivatives marginally affected the surface expression of cluster of differentiation (CD)80 and CD86 on BMMCs in the presence of LPS, although LPS alone did not increase the expression of those proteins. Therefore, benzoxazole derivatives inhibited the secretion of proinflammatory cytokines in mast cells and may be potential candidate anti‑allergic agents to suppress mast cell activation.

Vasoactive intestinal peptide regulates ileal goblet cell production in mice

“…The pathways involved in goblet cell signaling with neurons, immune cells, or both, remain poorly understood. Treatment with the bacterial cell wall component LPS has been shown to increase mast cell activation (Cho, Park, Kim, Choo, & Lee, ). While mast cells have been observed to be involved in enteric neuro‐immune signaling (Buhner et al, ), and are known to have VIP‐receptors (Keita et al, ), there was no direct influence of LPS on the counts of goblet cells incorporating GalNaz ex vivo in any of the present experiments.…”