TNF Production in Activated RBL-2H3 Cells Requires Munc13-4

Ayo, Tolulope E.; Adhikari, Pratikshya; Sugita, Shuzo; Xu, Hao

doi:10.1007/s10753-019-01161-4

Cited by 6 publications

(1 citation statement)

References 52 publications

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“…Activated mast cells can produce and release various cytokines, including TNF-α [34][35][36]. Therefore, we investigated the effect of Met on cytokine release mediated by DNP-HSA.…”

Section: Suppression Of Ag/ige-induced Cytokine Production By Metmentioning

confidence: 99%

Methiothepin downregulates SNAP‐23 and inhibits degranulation of rat basophilic leukemia cells and mouse bone marrow‐derived mast cells

Kondo,

Suzuki,

Matsumura

et al. 2023

Eur J Immunol

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In the present study, we found that methiothepin (a non‐selective 5‐hydroxytryptamine (5‐HT) receptor antagonist) inhibited antigen‐induced degranulation in rat basophilic leukemia cells and mouse bone marrow‐derived mast cells. Although antigen stimulation induces release of histamine and serotonin (5‐HT) by exocytosis and mast cells express several types of 5‐HT receptor, the detailed role of these receptors remains unclear. Here, pretreatment of cells with methiothepin attenuated increased intracellular Ca2+ concentration, phosphorylated critical upstream signaling components: SFKs, Syk, and PLCγ1, and suppressed TNF‐α secretion via inhibition of Akt and ERK phosphorylation. Furthermore, it inhibited PMA/ionomycin‐induced degranulation; this finding suggested that methiothepin affected downstream signaling. IκB kinase β (IKKβ) phosphorylates synaptosomal associated protein 23 (SNAP23), which regulates the fusion events of the secretory granule/plasma membrane after mast cell activation, resulting in degranulation. We showed that methiothepin blocked PMA/ionomycin‐induced phosphorylation of SNAP23 by inhibiting its interaction with IKKβ. Together with the results of selective 5‐HT antagonists, it is suggested that methiothepin inhibits mast cell degranulation by downregulating upstream signaling pathways and exocytotic fusion machinery through mainly 5‐HT1A receptor. Our findings provide that 5‐HT antagonists may be used to relieve allergic reactions.This article is protected by copyright. All rights reserved

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“…Activated mast cells can produce and release various cytokines, including TNF-α [34][35][36]. Therefore, we investigated the effect of Met on cytokine release mediated by DNP-HSA.…”

Section: Suppression Of Ag/ige-induced Cytokine Production By Metmentioning

confidence: 99%