Resveratrol suppresses TH2 cytokine production linked to MAPK activation in IgE‐antigen complex‐exposed basophilic mast cells (1045.31)

Background: Microbial infection or exposure to endotoxin later in life exacerbates established asthma. Mast cells are involved in the exacerbation of asthma. This exacerbation involves a toll-like receptor (TLR)–mediated response of mast cells. In the clinical practice of otolaryngology, otolaryngologists experience an exacerbation of nasal congestion when infectious rhinitis develops in patients with allergic rhinitis, but the mechanisms are unknown. Therefore, this study investigated the effect of lipopolysaccharide (LPS) on allergic rhinitis using a mouse allergic rhinitis model. Methods: Female BALB/c mice, TLR4 gene mutant C3H/HeJ mice or mast cell–deficient WBB6F1-W/Wv mice were sensitized intraperitoneally with ovalbumin (OVA)/alum, and were intranasal challenged with OVA and/or LPS. Nasal symptoms and histologic changes were examined. Cytokines in nasal tissue were examined by Western blot. The effects of LPS on degranulation and cytokine production of bone marrow–derived mast cells (BMMCs) were investigated. Results: Nasal administration of LPS together with the antigen exacerbated nasal symptoms, eosinophil infiltration of the nasal mucosa, and increased IL-5 production in the nasal mucosa. It was not observed in C3H/HeJ mice and WBB6F1-W/Wv mice. The addition of LPS increased the production of IL-5 from BMMCs in a dose-dependent manner, but no effect on degranulation was observed. Conclusions: Intranasal administration of LPS exacerbates allergic rhinitis through Th2 cytokine production from mast cells. This observation provides clues to the mechanism of exacerbation of allergic rhinitis caused by an infection in daily clinical practice.

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TIM-1 and TIM-3 enhancement of Th2 cytokine production by mast cells

Blood ◽

10.1182/blood-2006-11-058800 ◽

2007 ◽

Vol 110 (7) ◽

pp. 2565-2568 ◽

Cited By ~ 106

Author(s):

Susumu Nakae ◽

Motoyasu Iikura ◽

Hajime Suto ◽

Hisaya Akiba ◽

Dale T. Umetsu ◽

...

Keyword(s):

T Cell ◽

Mast Cells ◽

Immune Responses ◽

Cytokine Production ◽

Interleukin 4 ◽

Th2 Cells ◽

T Helper ◽

Th2 Cytokine ◽

Peritoneal Mast Cells

Members of the T-cell immunoglobulin– and mucin-domain–containing molecule (TIM) family have roles in T-cell–mediated immune responses. TIM-1 and TIM-2 are predominantly expressed on T helper type 2 (Th2) cells, whereas TIM-3 is preferentially expressed on Th1 and Th17 cells. We found that TIM-1 and TIM-3, but neither TIM-2 nor TIM-4, were constitutively expressed on mouse peritoneal mast cells and bone marrow–derived cultured mast cells (BMCMCs). After IgE + Ag stimulation, TIM-1 expression was down-regulated on BMCMCs, whereas TIM-3 expression was up-regulated. We also found that recombinant mouse TIM-4 (rmTIM-4), which is a ligand for TIM-1, as well as an anti–TIM-3 polyclonal Ab, can promote interleukin-4 (IL-4), IL-6, and IL-13 production without enhancing degranulation in BMCMCs stimulated with IgE + Ag. Moreover, the anti–TIM-3 Ab, but neither anti–TIM-1 Ab nor rmTIM-4, suppressed mast-cell apoptosis. These observations suggest that TIM-1 and TIM-3 may be able to influence T-cell–mediated immune responses in part through effects on mast cells.

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Inhibition of the Stem Cell Factor-Induced Migration of Mast Cells by Dexamethasone

Endocrinology ◽

10.1210/en.2003-0115 ◽

2003 ◽

Vol 144 (9) ◽

pp. 4080-4086 ◽

Cited By ~ 50

Author(s):

Hyun-Ja Jeong ◽

Ho-Jeong Na ◽

Seung-Heon Hong ◽

Hyung-Min Kim

Keyword(s):

Mast Cell ◽

Stem Cell ◽

Mast Cells ◽

P38 Mapk ◽

Stem Cell Factor ◽

Inflammatory Cytokine ◽

Cytokine Production ◽

Morphological Alteration ◽

Mapk Activation ◽

Inflammatory Cytokine Production

Abstract Mast cell accumulation can be causally related to several allergic inflammations. Previous work has demonstrated that glucocorticoids decreased tissue mast cell number, and stem cell factor (SCF)-induced migration of mast cells required p38 MAPK activation. In the present study we investigated the effects of dexamethasone on SCF-induced migration of rat peritoneal mast cells (RPMCs). SCF significantly induced the migration of RPMCs at 4 h. Dexamethasone dose-dependently inhibited SCF-induced migration of RPMCs (∼90.1% at 100 nm; P < 0.05). The MAPK p38 inhibitor SB203580 (20 μm) also inhibited the SCF-induced migration. The ability of SCF to enhance morphological alteration and filamentous actin formation was also abolished by treatment with dexamethasone. Dexamethasone inhibited SCF-induced p38 MAPK activation to near-basal levels and induced MAPK phosphatase-1 expression. In addition, SCF-induced inflammatory cytokine production was significantly inhibited by treatment with dexamethasone or SB203580 (P < 0.01). Our results show that dexamethasone potently regulates SCF-induced migration, p38 MAPK activation, and inflammatory cytokine production through the expression of MKP-1 protein in RPMCs. Such modulation may have functional consequences during dexamethasone treatment, especially mast cell-mediated allergic inflammation disorders.

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