Umbilical Cord Derived Mast Cells as Models for the Study of Inflammatory Diseases

Kourelis, Taxiarchis; Kempuraj, Duraisamy; Manola, Akrivi; Theoharides, Theoharis C.

doi:10.1002/9780470480151.ch8

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“…However, these cells vary enormously in their phenotypic characteristics owing to the age of the donor, site of skin used, degree of inflammation, or the presence of adipocytokines. The primary mast cells that we used were isolated from umbilical cord blood collected from healthy donors after uncomplicated deliveries, which have been well characterized (54). At 12 wk, these cells express the major granule mediator tryptase (Fig.…”

Section: Discussionmentioning

confidence: 99%

SP and IL-33 together markedly enhance TNF synthesis and secretion from human mast cells mediated by the interaction of their receptors

Taracanova

Alevizos

Karagkouni

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The peptide substance P (SP) and the cytokine tumor necrosis factor (TNF) have been implicated in inflammatory processes. Mast cells are recognized as important in inflammatory responses. Here, we report that IL-33 (30 ng/mL), a member of the IL-1 family of cytokines, administered in combination with SP (1 μM), markedly increase (by 1,000-fold) TNF gene expression in cultured human LAD2 and primary mast cells derived from umbilical cord blood. SP (0.01-1 μM) and IL-33 (1-100 ng/mL) in combination also greatly stimulate TNF secretion (by 4,500-fold). Pretreatment of LAD2 cells with two different neurokinin-1 (NK-1) receptor antagonists and siRNA inhibits TNF secretion by 50% (P < 0.001) when stimulated by SP and IL-33. Pretreatment of LAD2 cells with a neutralizing antibody for IL-33 receptor, ST2, inhibits TNF secretion by 50% (P < 0.001), and ST2 siRNA decreases TNF secretion by 30% (P < 0.05), when stimulated by SP and IL-33. Surprisingly, NK-1 antagonists also inhibit 50% of TNF secretion (P < 0.001) when stimulated only by IL-33, and ST2 receptor reduction also decreases SP-stimulated TNF secretion by 30% (P < 0.05), suggesting an interaction between NK-1 and ST2 receptors. Moreover, IL-33 increases NK-1 gene and surface protein expression, as well as IKβ-α phosphorylation. Pretreatment of LAD2 cells with 5,7,3′,4′-tetramethoxyflavone (methoxyluteolin) (1-100 μM) inhibits (P < 0.001) TNF gene expression (98%) and secretion (64%) at 50 μM and phosphorylation of p-IKB-α at 1 μM when stimulated by SP and IL-33. These findings identify a unique amplification process of TNF synthesis and secretion via the interaction of NK-1 and ST2 receptors inhibitable by methoxyluteolin. mast cells | substance P | interleukin-33 | tumor necrosis factor | inflammation

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Section: Discussionmentioning

confidence: 99%