An indoxyl compound 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, suppresses activation of Fyn kinase in mast cells and IgE-mediated allergic responses in mice

Lee, Jun Ho; Kim, Tae Hyung; Kim, Hyuk Soon; Kim, Aram; Kim, Do Kyun; Nam, Seung Taek; Park, Young Hwan; Her, Erk; Park, Yeong Min; Kim, Hyung Sik; Kim, Young Mi; Choi, Wahn Soo

doi:10.1016/j.taap.2015.04.009

Cited by 6 publications

(3 citation statements)

References 49 publications

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“…It is speculated that while Fyn may be useful for implantation, later in gestation it is detrimental for the maintenance of normal pregnancy. Based on previously reported proinflammatory roles of Fyn, and combining with the positive correlation, we observed in expression levels between Fyn and ROR‐γt, a indicative transcription factor of Th17 cell differentiation, the involvement of Fyn in Th17 cell regulation may be responsible for its low expression during pregnancy. The role of Fyn in implantation requires further investigation and may be associated with inflammation, cell adhesion and migration …”

Section: Discussionsupporting

confidence: 69%

Fyn Plays a Pivotal Role in Fetomaternal Tolerance Through Regulation of Th17 Cells

Liu

Tian

Xie

et al. 2016

American J Rep Immunol

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Section: Discussionsupporting

confidence: 69%

Fyn Plays a Pivotal Role in Fetomaternal Tolerance Through Regulation of Th17 Cells

Liu

Tian

Xie

et al. 2016

American J Rep Immunol

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“…The candidate drugs targeting MC maturation, development and homing to the gut as well as MC activation and major mediators are under development, some of which show benefit to IBS symptoms improvement (Table 2). [92][93][94][95][96][97][98][99][100][101][102] Disodium cromoglycate (DSCG) and ketotifen are 2 kinds of classical MC stabilizers and are available for IBS. Preliminary clinical data indicated that a 6 month of DSCG treatment significantly reduced release of tryptase from jejunal biopsies, and increased clinical improvement of bowel function in D-IBS.…”

Section: Mast Cells As Potential Therapeutic Target For Irritable Bowmentioning

confidence: 99%

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Zhang

Song

Hou

2016

J Neurogastroenterol Motil

111

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Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder since it lacks demonstrable pathological abnormalities. However, in recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel, has been observed in some patients with IBS. The close association of mast cells with major intestinal functions, such as epithelial secretion and permeability, neuroimmune interactions, visceral sensation, and peristalsis, makes researchers and gastroenterologists to focus attention on the key roles of mast cells in the pathogenesis of IBS. Numerous studies have been carried out to identify the mechanisms in the development, infiltration, activation, and degranulation of intestinal mast cells, as well as the actions of mast cells in the processes of mucosal barrier disruption, mucosal immune dysregulation, visceral hypersensitivity, dysmotility, and local and central stress in IBS. Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients, and have partially exhibited considerable efficacy. This review focuses on recent advances in the role of mast cells in IBS, with particular emphasis on bridging experimental data with clinical therapeutics for IBS patients.

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“…Fyn is a crucial signaling molecule for activation of mast cells stimulated by various antigens. Increasing reports have demonstrated that Gab2/PI3-K/Akt and Fyn/Syk pathway plays an essential role in the development of allergic diseases [ 21 , 22 ]. Interestingly, in our present study, we also found that AP could downregulate phosphorylated Fyn in anti-DNP IgE stimulated RBL-2H3 cells.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Angelica Polysaccharide on Activation of Mast Cells

Mao

Sun

Mao

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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This study was designed to investigate the inhibitory effects of Angelica polysaccharide (AP) on activation of mast cells and its possible molecular mechanism. In our study, we determined the proinflammatory cytokines and allergic mediators in anti-DNP IgE stimulated RBL-2H3 cells and found that AP (50, 100, and 200 μg/mL) significantly decreased the release of histamine, β-hexosaminidase, leukotrienes C4 (LTC4), IL-1, IL-4, TNF-α, IL-6, and human monocyte chemotactic protein-1 (MCP-1/CCL2) (p < 0.05). In addition, Ca2+ entry was inhibited by treatment with AP. AP also downregulated the protein expressions of p-Fyn, p-Akt, p-P38, IL-4, TNF-α, and NF-κB p65 in both Fyn gene upregulated and normal RBL-2H3 cells (p < 0.05). Collectively, our results showed that AP could inhibit the activation of mast cells via suppressing the releases of proinflammatory cytokines allergic mediators, Gab2/PI3-K/Akt and Fyn/Syk pathways.

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An indoxyl compound 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, suppresses activation of Fyn kinase in mast cells and IgE-mediated allergic responses in mice

Cited by 6 publications

References 49 publications

Fyn Plays a Pivotal Role in Fetomaternal Tolerance Through Regulation of Th17 Cells

Fyn Plays a Pivotal Role in Fetomaternal Tolerance Through Regulation of Th17 Cells

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Inhibitory Effects of Angelica Polysaccharide on Activation of Mast Cells

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