Mast Cell-Mediated Allergic Response Is Suppressed by Sophorae Flos: Inhibition of Src-Family Kinase

2008 ◽  
Vol 233 (10) ◽  
pp. 1271-1279 ◽  
Author(s):  
Jun Ho Lee ◽  
Jie Wan Kim ◽  
Na Young Ko ◽  
Se Hwan Mun ◽  
Do Kyun Kim ◽  
...  
Keyword(s):  
Mast Cells ◽  
Map Kinases ◽  
Herbal Medicines ◽  
Inhibitory Effect ◽  
Allergic Response ◽  
Src Family Kinase ◽  
Potent Effect ◽  
Alternative Medicines ◽  
Ige Mediated

Complementary and alternative medicines are considered as a promising direction for the development of anti-allergic therapies in oriental countries. We screened approximately 100 oriental herbal medicines for anti-allergic activity. Sophorae flos exhibited the most potent effect on degranulation in antigen-stimulated mast cells. We further investigated the effect of Sophorae flos on the IgE-mediated allergic response in vivo and its mechanism of action in mast cells. Sophorae flos exhibited a significant inhibitory effect on degranulation in antigen-stimulated mast cells with IC50 values of ~31.6 μg/mL (RBL-2H3 mast cells) and ~47.8 μg/mL (bone marrow-derived mast cells). Sophorae flos also suppressed the expression and secretion of TNF-α and IL-4 in the cells and IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. Sophorae flos inhibited the activating phosphorylation of Syk and LAT in mast cells. Further downstream, activating phosphorylation of Akt and the prototypic MAP kinases, namely, p38, ERK1/2, and JNK, were also inhibited. These results suggest that Sophorae flos inhibits the Src family kinase-dependent signaling cascades in mast cells and may thus exert anti-allergic activity.

Coupling of M2 muscarinic receptors to ERK MAP kinases and caldesmon phosphorylation in colonic smooth muscle

2000 ◽  
Vol 278 (3) ◽  
pp. G429-G437 ◽  
Author(s):  
Amy K. Cook ◽  
Michael Carty ◽  
Cherie A. Singer ◽  
Ilia A. Yamboliev ◽  
William T. Gerthoffer
Keyword(s):  
Smooth Muscle ◽  
Map Kinase ◽  
Muscarinic Receptors ◽  
Map Kinases ◽  
Kinase Inhibitor ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Subsequent Treatment ◽  
P38 Map Kinase

Coupling of M2 and M3 muscarinic receptors to activation of mitogen-activated protein (MAP) kinases and phosphorylation of caldesmon was studied in canine colonic smooth muscle strips in which M3 receptors were selectively inactivated by N, N-dimethyl-4-piperidinyl diphenylacetate (4-DAMP) mustard (40 nM). ACh elicited activation of extracellular signal-regulated kinase (ERK) 1, ERK2, and p38 MAP kinases in control muscles and increased phosphorylation of caldesmon (Ser789), a putative downstream target of MAP kinases. Alkylation of M3 receptors with 4-DAMP had only a modest inhibitory effect on ERK activation, p38 MAP kinase activation, and caldesmon phosphorylation. Subsequent treatment with 1 μM AF-DX 116 completely prevented activation of ERK and p38 MAP kinase and prevented caldesmon phosphorylation. Caldesmon phosphorylation was blocked by the MAP kinase/ERK kinase inhibitor PD-98509 but not by the p38 MAP kinase inhibitor SB-203580. These results indicate that colonic smooth muscle M2 receptors are coupled to ERK and p38 MAP kinases. Activation of ERK, but not p38 MAP kinases, results in phosphorylation of caldesmon in vivo, which is a novel function for M2receptor activation in smooth muscle.

Morin inhibits Fyn kinase in mast cells and IgE-mediated type I hypersensitivity response in vivo

2009 ◽  
Vol 77 (9) ◽  
pp. 1506-1512 ◽  
Author(s):  
Jie Wan Kim ◽  
Jun Ho Lee ◽  
Bang Yeon Hwang ◽  
Se Hwan Mun ◽  
Na Young Ko ◽  
...  
Keyword(s):  
Mast Cells ◽  
Type I ◽  
Hypersensitivity Response ◽  
Fyn Kinase ◽  
Ige Mediated ◽  
Type I Hypersensitivity

Aqueous Extract of Mosla chinensis Inhibits Mast Cell-Mediated Allergic Inflammation

2012 ◽  
Vol 40 (06) ◽  
pp. 1257-1270 ◽  
Author(s):  
Hui-Hun Kim ◽  
Jin-Su Yoo ◽  
Tae-Yong Shin ◽  
Sang-Hyun Kim
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Histamine Release ◽  
Aqueous Extract ◽  
Proinflammatory Cytokines ◽  
Immunoglobulin E ◽  
Inflammatory Diseases ◽  
Allergic Inflammation ◽  
Inhibitory Effect ◽  
Ige Mediated

Allergic inflammatory diseases such as food allergy, asthma, sinusitis, and atopic dermatitis are increasing worldwide. In this study, we investigated the effects of aqueous extract of Mosla chinensis Max. (AMC) on mast cell-mediated allergic inflammation and studied the possible mechanism of this action. AMC inhibited compound 48/80-induced systemic and immunoglobulin E (IgE)-mediated local anaphylaxis. AMC reduced intracellular calcium levels and downstream histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. In addition, AMC decreased gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 in human mast cells. The inhibitory effect of AMC on cytokine expression was nuclear factor (NF)-κB dependent. Our results indicate that AMC inhibits mast cell-mediated allergic inflammatory reaction by suppressing histamine release and expression of proinflammatory cytokines and the involvement of calcium and NF-κB in these effects. AMC might be a possible therapeutic candidate for allergic inflammatory disorders.

scholarly journals Evolutionary background of allergic reactivity: mast cells, FcεRI, IgE - three components of the effector phase of the allergic response

2018 ◽  
Vol 15 (4) ◽  
pp. 5-16
Author(s):  
I S Gushchin
Keyword(s):  
Mast Cells ◽  
Immunoglobulin E ◽  
The Body ◽  
Allergic Response ◽  
Effector Phase ◽  
Time Regime ◽  
High Affinity Receptor ◽  
Ige Mediated ◽  
Affinity Receptor ◽  
Elimination Function

The literature data on the evolution of the main obligatory participants in the effector phase of the IgE-mediated allergic response are presented: mast cells/basophils, immunoglobulin E, and high affinity receptor for the Fcε fragment (FcεRI). Allergic reactivity is considered as the most recent evolutionary immunologically-mediated acquisition of mammals. It is aimed at recognizing small amounts of allergen entering the body in a certain time regime, and organizing an allergen-specific inflammation that carries features of elimination function. The most biologically justified way to prevent allergies is to restore the function of barrier systems and, accordingly, to prevent the need to develop an allergic response.

Lipopolysaccharide and proinflammatory cytokines stimulate interleukin-6 expression in C2C12 myoblasts: role of the Jun NH2-terminal kinase

2003 ◽  
Vol 285 (5) ◽  
pp. R1153-R1164 ◽  
Author(s):  
Robert A. Frost ◽  
Gerald J. Nystrom ◽  
Charles H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Map Kinases ◽  
Kinase Inhibitors ◽  
Inhibitory Effect ◽  
C2c12 Myoblasts ◽  
Downstream Target ◽  
Tnf Α ◽  
Inflammatory Stimuli

IL-6 is a major inflammatory cytokine that plays a central role in coordinating the acute-phase response to trauma, injury, and infection in vivo. Although IL-6 is synthesized predominantly by macrophages and lymphocytes, skeletal muscle is a newly recognized source of this cytokine. IL-6 from muscle spills into the circulation, and blood-borne IL-6 can be elevated >100-fold due to exercise and injury. The purpose of the present study was to determine whether inflammatory stimuli, such as LPS, TNF-α, and IL-1β, could increase IL-6 expression in skeletal muscle and C2C12 myoblasts. Second, we investigated the role of mitogen-activated protein (MAP) kinases, and the Jun NH2-terminal kinase (JNK) in particular, as a mediator of this response. Intraperitoneal injection of LPS in mice increased the circulating concentration of IL-6 from undetectable levels to 4 ng/ml. LPS also increased IL-6 mRNA 100-fold in mouse fast-twitch skeletal muscle. Addition of LPS, IL-1β, or TNF-α directly to C2C12 myoblasts increased IL-6 protein (6- to 8-fold) and IL-6 mRNA (5- to 10-fold). The response to all three stimuli was completely blocked by the JNK inhibitor SP-600125 but not as effectively by other MAP kinase inhibitors. SP-600125 blocked LPS-stimulated IL-6 synthesis dose dependently at both the RNA and protein level. SP-600125 was as effective as the synthetic glucocorticoid dexamethasone at inhibiting IL-6 expression. SP-600125 inhibited IL-6 synthesis when added to cells up to 60 min after LPS stimulation, but its inhibitory effect waned with time. LPS stimulated IL-6 mRNA in both myoblasts and myotubes, but myoblasts showed a proportionally greater LPS-induced increase in IL-6 protein expression compared with myotubes. SP-600125 and the proteasomal inhibitor MG-132 blocked LPS-induced degradation of IκB-α/ϵ and LPS-stimulated expression of IκB-α mRNA. Yet, only SP-600125 and not MG-132 blocked LPS-induced IL-6 mRNA expression. This suggests that IL-6 gene expression is a downstream target of JNK in C2C12 myoblasts.

scholarly journals Inhibitory effect of fermented Arctium lappa fruit extract on the IgE-mediated allergic response in RBL-2H3 cells

2015 ◽  
Vol 37 (2) ◽  
pp. 501-508 ◽  
Author(s):  
JAE-MYUNG YOO ◽  
JU HYE YANG ◽  
HYE JIN YANG ◽  
WON-KYUNG CHO ◽  
JIN YEUL MA
Keyword(s):  
Inhibitory Effect ◽  
Allergic Response ◽  
Fruit Extract ◽  
Arctium Lappa ◽  
Ige Mediated

Spiraeoside inhibits mast cells activation and IgE-mediated allergic responses by suppressing phospholipase C-γ-mediated signaling

2015 ◽  
Vol 93 (3) ◽  
pp. 227-235 ◽  
Author(s):  
Jung Kuk Kim ◽  
Young-Kyo Seo ◽  
Sehoon Park ◽  
Soo-Ah Park ◽  
Seyoung Lim ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Phospholipase C ◽  
Cell Activation ◽  
Mapk Signaling ◽  
Mast Cell Activation ◽  
Tnf Α ◽  
Ige Mediated ◽  
Subsequent Activation

Mast cells are responsible for IgE-mediated allergic responses through the secretion of various inflammatory cytokines and mediators. Therefore, the pharmacological regulation of mast cell activation is an important goal in the development of novel anti-allergic drugs. In this study, we found that spiraeoside (SP) inhibits mast cell activation and allergic responses in vivo. SP dose-dependently inhibited the degranulation induced by IgE-antigen (Ag) stimulation in RBL-2H3 mast cells without cytotoxic effects. At the molecular level, SP reduced the Ag-induced phosphorylation and subsequent activation of phospholipase C-γ2 (PLC-γ2). Moreover, SP inhibited the phosphorylation of spleen tyrosine kinase (Syk), linker for activation of T cells (LAT), and downstream MAPKs, such as ERK1/2, p38, and JNK, eventually attenuating expression of TNF-α and IL-4. Finally, we found that SP significantly inhibited IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. Taken together, our results strongly suggest that SP suppresses IgE-mediated mast cell activation and allergic responses by inhibiting Lyn-induced PLC-γ2/MAPK signaling in mast cells.

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