Specific signaling pathways in the regulation of TNF-α mRNA synthesis and TNF-α secretion in RBL-2H3 mast cells stimulated through the high affinity IgE receptor

Pelletier, Claire; Guérin-Marchand, Claudine; Iannascoli, Bruno; Marchand, Françoise; David, B.; Weyer, A.; Blank, Ulrich

doi:10.1007/s000110050364

Cited by 36 publications

(24 citation statements)

References 30 publications

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“…The supernatants were collected, clarified by centrifugation to remove any detached cells, and TNF-␣ quantified by specific ELISA (BioSource International), according to the manufacturer's instructions. The percentage of cell-associated TNF-␣ was determined by washing the cell monolayer with HBSS and freeze thawing the cells recovered from the wells by trypsinization in HBSS-containing protease inhibitors three times (25).…”

Section: Cell-associated and Secreted Tnf-␣mentioning

confidence: 99%

“…The cytokine TNF-␣ is important in host defense against bacterial infection, and has been reported to be both stored in granules in RBL mast cells and newly synthesized upon IgE receptor crosslinking (25). In two preliminary experiments, we compared TNF-␣ secretion between control PC6 and Lyn unique domain UC3 transfectants after the cells were stimulated for 2.5 h with moderate valency DNP 10 BSA Ag.…”

Section: Cell-associated and Fc⑀ri-induced Tnf-␣ Production In Lyn Unmentioning

confidence: 99%

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Regulation of Rat Basophilic Leukemia-2H3 Mast Cell Secretion by a Constitutive Lyn Kinase Interaction with the High Affinity IgE Receptor (FcεRI)

Vonakis

Gibbons

Rotté

et al. 2005

The Journal of Immunology

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Signaling through the high affinity IgE receptor is initiated by noncovalently associated Lyn kinase, resulting in the secretion of inflammatory mediators from mast cells. A fraction of the total cellular Lyn is associated via its N-terminal unique domain with the cytoplasmic domain of the FcεRI β subunit before receptor aggregation. In the current study, we stably transfected the unique domain of Lyn into rat basophilic leukemia-2H3 mast cells and examined the consequences on FcεRI-induced signal transduction and mediator secretion to further define the role of the unique domain of Lyn in mast cell secretion. Tyrosine phosphorylation of FcεRI β and γ subunits was partially inhibited in the Lyn unique domain transfectants after Ag stimulation. Ag stimulation of Lyn unique domain transfectants was accompanied by enhanced phosphorylation of MEK and ERK-2, which are required for leukotriene C4 (LTC4) release, and production of LTC4 was increased 3- to 5-fold, compared with cells transfected with vector alone. Conversely, tyrosine phosphorylation of the adaptor protein Gab2, which is essential for mast cell degranulation, was inhibited after Ag stimulation of Lyn unique domain transfectants, and Ag-induced release of histamine was inhibited up to 48%. In rat basophilic leukemia-2H3 cells, Lyn thus plays a dual role by positively regulating FcεRI phosphorylation and degranulation while negatively regulating LTC4 production. This study provides further evidence that the constitutive interaction between the unique domain of Lyn and the FcεRI β subunit is a crucial step in the initiation of FcεRI signaling and that Lyn is limiting for FcεRI-induced secretion of inflammatory mediators.

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Section: Cell-associated and Secreted Tnf-␣mentioning

confidence: 99%

Section: Cell-associated and Fc⑀ri-induced Tnf-␣ Production In Lyn Unmentioning

confidence: 99%

Regulation of Rat Basophilic Leukemia-2H3 Mast Cell Secretion by a Constitutive Lyn Kinase Interaction with the High Affinity IgE Receptor (FcεRI)

Vonakis

Gibbons

Rotté

et al. 2005

The Journal of Immunology

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“…Activation of these newly recruited PTKs, in turn, facilitates the translocation and phosphorylation of multiple substrates, including phospholipase C␥ (PLC␥) isozymes and . Although the involvement of PI3K in antigen-induced degranulation is established (7)(8)(9)(10)(11), a clear consensus regarding how lipid products derived from the action of PI3K mediate the cellular responses has yet to emerge. Putative downstream targets for PI(3,4,5)P 3 and PI(3,4)P 2 include SH2-or pleckstrin homology (PH) domain-containing signaling enzymes such as PLC-␥, Akt, and Bruton's tyrosine kinase (Btk) (12,13), which transduce the signal to the respective signaling pathways.…”

mentioning

confidence: 99%

Phosphoinositide 3-Kinase Facilitates Antigen-stimulated Ca2+ Influx in RBL-2H3 Mast Cells via a Phosphatidylinositol 3,4,5-Trisphosphate-sensitive Ca2+Entry Mechanism

Ching

Hsu

Johnson

et al. 2001

Journal of Biological Chemistry

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This study presents evidence that phosphoinositide 3-kinase (PI3K) plays a concerted role with phospholipase C␥ in initiating antigen-mediated Ca 2؉ signaling in mast cells via a phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P 3 )-sensitive Ca 2؉ entry pathway. Exogenous PI(3,4,5)P 3 at concentrations close to its physiological level induces instantaneous Ca 2؉ influx into RBL-2H3 cells. This PI(3,4,5)P 3 -induced intracellular Ca 2؉ increase is independent of phospholipase C activity or the depletion of internal stores. ) and diacylglycerol, which induce the release of Ca 2ϩ from intracellular stores and the activation of protein kinase C, respectively. On the other hand, stimulation of PI3K results in transient accumulation of micromolar levels of phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P 3 ) and phosphatidylinositol 3,4-bisphosphate (PI(3,4)P 2 ). Although the involvement of PI3K in antigen-induced degranulation is established (7-11), a clear consensus regarding how lipid products derived from the action of PI3K mediate the cellular responses has yet to emerge. Putative downstream targets for PI(3,4,5)P 3 and PI(3,4)P 2 include SH2-or pleckstrin homology (PH) domain-containing signaling enzymes such as PLC-␥, Akt, and Bruton's tyrosine kinase (Btk) (12, 13), which transduce the signal to the respective signaling pathways. In addition, data from several laboratories suggest a role of PI3K in the regulation of intracellular Ca 2ϩ ([Ca 2ϩ ] i ) increase in mast cells (9,11,14). Evidence suggests that PI3K may mediate [Ca 2ϩ ] i elevation in mast cells via two distinct mechanisms. First, in vitro data indicate that PI(3,4,5)P 3 stimulates Ins(1,4,5)P 3 production by activating PLC␥ isozymes (15,16). This PLC␥ activation may be attained directly by facilitating membrane translocation (15, 16) or indirectly via Btk (14, 17). Second, PI3K may increase [Ca 2ϩ ] i by facilitating Ca 2ϩ mobilization across plasma membranes (11). This premise was prompted by data showing the inhibitory effect of PI3K inhibitors on antigen-induced Ca 2ϩ response (9,11,14), and is in * This work was supported by National Institutes of Health Grant GM53448. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.‡ To whom correspondence should be addressed: College of Pharmacy, The Ohio State University, 500 West 12th Ave., Columbus, OH 43210-1291. Tel.: 614-688-4008; Fax: 614-688-8556; E-mail: chen@ dendrite.pharmacy.ohio-state.edu.1 The abbreviations used are: Fc⑀RI, the high affinity receptor for IgE; PI3K, phosphoinositide 3-kinase; PLC, phospholipase C; PI(3,4,5)P 3 , phosphatidylinositol 3,4,5-trisphosphate; PI(3,4)P 2 , phosphatidylinositol 3,4-bisphosphate; PI(4,5)P 2 , phosphatidylinositol 4,5-bisphosphate; PI(3)P, phosphatidylinositol 3-monophosphate; Ins(1,4,5)P 3 , D-myo-inositol 1,4,5-trisphosphate; Ins(1,3,4,5)P 4 , Dmyo-inositol 1,3,4...

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“…The role of the mast cell in SLE pathogeny currently represents an interesting issue, due to the enormous potential to synthesize and release inflammatory factors [36]. However, there are no data which correlate the number of mast cells with SLE severity.…”

Section: Mast Cellsmentioning

confidence: 99%

A brief insight into systemic lupus erythematosus pathogenesis

Azoicai¹,

Căruntu²

2016

Arch Clin Cases

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Systemic lupus erythematosus is an autoimmune disease which afflicts many systems. The precise pathogenesis is still unclear, but strong evidences sustain a multifactorial mechanism, based on the interaction of various genetic, epigenetic, environment, hormonal and immune-regulatory factors. Nowadays, the research interest focuses on cellular and molecular alterations, as results of the complexity of apoptotic process and immune responses acting as initiators and leading to tissue injury. The paper points out on key pathogenic cells, molecules and processes involved in SLE pathogenesis, namely B and T lymphocytes, mast cells, apoptosis, complement system and oxidative stress.

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Specific signaling pathways in the regulation of TNF-α mRNA synthesis and TNF-α secretion in RBL-2H3 mast cells stimulated through the high affinity IgE receptor

Abstract: Our results show that in FcepsilonRI-stimulated RBL-2H3 cells calcium mobilization, activation of PKC and PI 3-kinase are necessary for TNF-alpha secretion while for the increased TNF-alpha mRNA expression PKC activity is dispensable and PI 3-kinase activity only partially required.

Cited by 36 publications

References 30 publications

Regulation of Rat Basophilic Leukemia-2H3 Mast Cell Secretion by a Constitutive Lyn Kinase Interaction with the High Affinity IgE Receptor (FcεRI)

Regulation of Rat Basophilic Leukemia-2H3 Mast Cell Secretion by a Constitutive Lyn Kinase Interaction with the High Affinity IgE Receptor (FcεRI)

Phosphoinositide 3-Kinase Facilitates Antigen-stimulated Ca2+ Influx in RBL-2H3 Mast Cells via a Phosphatidylinositol 3,4,5-Trisphosphate-sensitive Ca2+Entry Mechanism

A brief insight into systemic lupus erythematosus pathogenesis

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