Imidacloprid exposure suppresses cytokine production and neutrophil infiltration in TLR2-dependent activation of RBL-2H3 cells and skin inflammation of BALB/c mice

2020 ◽  
Vol 44 (45) ◽  
pp. 19489-19498
Author(s):  
Linbo Shi ◽  
Huaping Xu ◽  
Fangfang Min ◽  
Xin Li ◽  
Xiaoyun Shi ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cytokine Production ◽  
Neutrophil Infiltration ◽  
Skin Inflammation ◽  
Mast Cell Degranulation ◽  
Tnf Α

Imidacloprid suppressed TNF-α and IL-6 production and neutrophil infiltration, without altering mast cell degranulation.

scholarly journals TLR2 Regulates Mast Cell IL-6 and IL-13 Production During Listeria monocytogenes Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Rodolfo Soria-Castro ◽  
Ángel R. Alfaro-Doblado ◽  
Gloria Rodríguez-López ◽  
Marcia Campillo-Navarro ◽  
Yatsiri G. Meneses-Preza ◽  
...  
Keyword(s):  
Mast Cell ◽  
Listeria Monocytogenes ◽  
Cytokine Production ◽  
Bacterial Load ◽  
Mast Cell Degranulation ◽  
Signaling Proteins ◽  
Ros Production ◽  
Tnf Α ◽  
Listeria Monocytogenes Infection ◽  
Activation Pathways

Listeria monocytogenes (L.m) is efficiently controlled by several cells of the innate immunity, including the Mast Cell (MC). MC is activated by L.m inducing its degranulation, cytokine production and microbicidal mechanisms. TLR2 is required for the optimal control of L.m infection by different cells of the immune system. However, little is known about the MC receptors involved in recognizing this bacterium and whether these interactions mediate MC activation. In this study, we analyzed whether TLR2 is involved in mediating different MC activation responses during L.m infection. We found that despite MC were infected with L.m, they were able to clear the bacterial load. In addition, MC degranulated and produced ROS, TNF-α, IL-1β, IL-6, IL-13 and MCP-1 in response to bacterial infection. Interestingly, L.m induced the activation of signaling proteins: ERK, p38 and NF-κB. When TLR2 was blocked, L.m endocytosis, bactericidal activity, ROS production and mast cell degranulation were not affected. Interestingly, only IL-6 and IL-13 production were affected when TLR2 was inhibited in response to L.m infection. Furthermore, p38 activation depended on TLR2, but not ERK or NF-κB activation. These results indicate that TLR2 mediates only some MC activation pathways during L.m infection, mainly those related to IL-6 and IL-13 production.

P-21 Activated Kinase 1 (Pak1) Is Critical for Normal Mast Cell Degranulation and Cytokine Production in Response to Antigen Stimulation of the High Affinity IgE Receptor.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 647-647
Author(s):  
Jayme D. Allen ◽  
Clemens Hoffman ◽  
Ethel Derr-Yellin ◽  
Waylan Bessler ◽  
Fen-Chun Yang ◽  
...  
Keyword(s):  
Mast Cell ◽  
Transcription Factors ◽  
Cytokine Production ◽  
De Novo ◽  
Mast Cell Degranulation ◽  
Ige Receptor ◽  
High Affinity ◽  
Cytokine Synthesis ◽  
High Affinity Ige Receptor ◽  
Stimulation Of

Abstract Mast cells participate in normal and pathogenic inflammatory processes, including innate host defense, allergy, and asthma. Stimulation of the mast cell high-affinity IgE receptor (FcεR) by receptor cross-linking activates multiple downstream signaling pathways resulting in degranulation and de novo synthesis of multiple cytokines. However, the molecular mechanisms underlying these processes are incompletely defined. It is known that Rac2 deficient murine bone marrow derived mast cells (BMMCs) have impaired degranulation, but the downstream effectors that modulate this function are unknown. We hypothesized that p-21 activated kinase 1 (Pak1), a downstream effector of Rac proteins, is important in degranulation and de novo cytokine synthesis. Mature BMMCs from wild-type (WT) and Pak1 KO mice were sensitized with anti-DNP IgE then stimulated with DNP-HSA to stimulate FcεR. Interestingly, Pak1 KO BMMCs showed significant impairment in degranulation, as demonstrated by a 3-fold reduction in the percent of B-hexosaminidase released upon IgE stimulation. IgE stimulation of mast cell results not only in degranulation, but also in the production of TNFα, which is critical in the early recruitment of neutrophils to sites of acute inflammation. TNFαsynthesis is influenced by a number of transcription factors, many which are regulated by Erk. Since Pak1 has been shown, in overexpression systems, to phosphorylate Raf and Mek to activate Erk, we examined Erk activation in WT and Pak1 KO BMMCs in response to IgE stimulation. Pak1 KO BMMCs have a 50% reduction in phospho-Erk as compared to controls. We then tested another MAPK member important in mast cell cytokine synthesis, p38, and found phospho-p38 to be decreased in Pak1 KO BMMCs as well. Further, IgE-stimulated Pak1 KO BMMCs produce only 20–30% as much TNFαas controls. To define the role of Pak1 in cytokine production as specific for TNFαversus a more global defect, we also studied IL-6 synthesis and are able to report a 50% reduction in IL-6 production by Pak1 KO BMMCs. Our results indicate that Pak1 is important in BMMC degranulation, cytokine production, and MAPK activation in response to FcεR stimulation. These studies identify Pak1 as a potential therapeutic target in pathologic inflammation. Mechanisms by which Pak1 may be influencing mast cell degranulation as well as further study of transcription factors important in mast cell cytokine production are under current investigation.

scholarly journals Allergic Airway-Induced Hypersensitivity Is Attenuated by Bergapten in Murine Models of Inflammation

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Douglas B. Aidoo ◽  
David D. Obiri ◽  
Newman Osafo ◽  
Aaron O. Antwi ◽  
Leslie B. Essel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mast Cell ◽  
Protein Concentration ◽  
Allergic Inflammation ◽  
Neutrophil Infiltration ◽  
Lavage Fluid ◽  
Mast Cell Degranulation ◽  
Murine Models

Bergapten (5-methoxypsoralen, 5-MOP) is a plant-derived furocoumarin with demonstrated anti-inflammatory action. The present study investigated its effects on allergic inflammation in two related pathways of mast cell degranulation. Compound 48/80 and lipopolysaccharide (LPS) were used to activate the IgE-independent pathway while bovine serum albumin (BSA) was used as allergen for the IgE-dependent pathway. The modulatory effect of bergapten on mast cell degranulation, neutrophil extravasation, protein concentration, lung histopathology, and oxidative stress was assessed. Bergapten at 10, 30, and 100 μg/ml for 15 min stabilized mast cells in rat mesenteric tissue from disruption in vitro and when administered in vivo at 3, 10, and 30 mg kg−1 for 1 h protected mice from fatal anaphylaxis induced by compound 48/80. Similarly, treatment of LPS-challenged mice with bergapten (3, 10, and 30 mg kg−1) for 24 h significantly decreased neutrophil infiltration into bronchoalveolar lavage fluid, mean protein concentration, and inflammatory cell infiltration of pulmonary tissues when compared to the saline-treated LPS-challenged control. In addition, lung histology of the bergapten-treated LPS-challenged mice showed significantly less oedema, congestion, and alveolar septa thickening when compared to the saline-treated LPS-challenged disease control. LPS-induced oxidative stress was significantly reduced through increased tissue activities of catalase and superoxide dismutase and reduced malondialdehyde levels on treatment with bergapten. In the triple antigen-induced active anaphylaxis, daily administration of bergapten at 3, 10, and 30 mg kg−1 for 10 days, respectively, protected previously sensitized and challenged mice against anaphylactic shock. Overall, our study demonstrates the ability of bergapten to attenuate allergic airway-induced hypersensitivity in murine models of inflammation, suggesting its possible therapeutic benefit in this condition.

scholarly journals Regulation of mast cell survival and function by tuberous sclerosis complex 1

Blood ◽  
2012 ◽  
Vol 119 (14) ◽  
pp. 3306-3314 ◽  
Author(s):  
Jinwook Shin ◽  
Hongjie Pan ◽  
Xiao-Ping Zhong
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Survival ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Cell Activation ◽  
Cytokine Production ◽  
Mast Cell Degranulation ◽  
Mtor Signaling ◽  
Mast Cell Activation

Abstract Mast cells play critical roles in allergic disorders and asthma. The importance of tuberous sclerosis complex 1/2-mammalian target of rapamycin (TSC1/2-mTOR) signaling in mast cells is unknown. Here, we report that TSC1 is a critical regulator for mTOR signaling in mast cells downstream of FcεRI and c-Kit, and differentially controls mast cell degranulation and cytokine production. TSC1-deficiency results in impaired mast cell degranulation, but enhanced cytokine production in vitro and in vivo after FcεRI engagement. Furthermore, TSC1 is critical for mast cell survival through multiple pathways of apoptosis including the down-regulation of p53, miR-34a, reactive oxygen species, and the up-regulation of Bcl-2. Together, these findings reveal that TSC1 is a critical regulator of mast cell activation and survival, suggesting the manipulation of the TSC1/2-mTOR pathway as a therapeutic strategy for mast cell-mediated diseases.

scholarly journals The Bcl10–Malt1 complex segregates FcεRI-mediated nuclear factor κB activation and cytokine production from mast cell degranulation

2006 ◽  
Vol 172 (4) ◽  
pp. i7-i7
Author(s):  
Stefanie Klemm ◽  
Jan Gutermuth ◽  
Lothar Hültner ◽  
Tim Sparwasser ◽  
Heidrun Behrendt ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cytokine Production ◽  
Nuclear Factor Κb ◽  
Mast Cell Degranulation ◽  
Nuclear Factor

scholarly journals Immune Response to Snake Envenoming and Treatment with Antivenom; Complement Activation, Cytokine Production and Mast Cell Degranulation

2013 ◽  
Vol 7 (7) ◽  
pp. e2326 ◽  
Author(s):  
Shelley F. Stone ◽  
Geoffrey K. Isbister ◽  
Seyed Shahmy ◽  
Fahim Mohamed ◽  
Chandana Abeysinghe ◽  
...  
Keyword(s):  
Immune Response ◽  
Mast Cell ◽  
Complement Activation ◽  
Cytokine Production ◽  
Mast Cell Degranulation

scholarly journals ELKS1 controls mast cell degranulation by regulating the transcription of Stxbp2 and Syntaxin 4 via Kdm2b stabilization

2020 ◽  
Vol 6 (31) ◽  
pp. eabb2497
Author(s):  
Hiu Yan Lam ◽  
Surendar Arumugam ◽  
Han Gyu Bae ◽  
Cheng Chun Wang ◽  
Sangyong Jung ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cytokine Production ◽  
Nuclear Factor Κb ◽  
Mast Cell Degranulation ◽  
Nuclear Factor ◽  
Regulated Exocytosis ◽  
Lysine Specific Demethylase ◽  
Syntaxin 4

ELKS1 is a protein with proposed roles in regulated exocytosis in neurons and nuclear factor κB (NF-κB) signaling in cancer cells. However, how these two potential roles come together under physiological settings remain unknown. Since both regulated exocytosis and NF-κB signaling are determinants of mast cell (MC) functions, we generated mice lacking ELKS1 in connective tissue MCs (Elks1f/f Mcpt5-Cre) and found that while ELKS1 is dispensable for NF-κB–mediated cytokine production, it is essential for MC degranulation both in vivo and in vitro. Impaired degranulation was caused by reduced transcription of Syntaxin 4 (STX4) and Syntaxin binding protein 2 (Stxpb2), resulting from a lack of ELKS1-mediated stabilization of lysine-specific demethylase 2B (Kdm2b), which is an essential regulator of STX4 and Stxbp2 transcription. These results suggest a transcriptional role for active-zone proteins like ELKS1 and suggest that they may regulate exocytosis through a novel mechanism involving transcription of key exocytosis proteins.

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