Nerve Growth Factor Induces the Expression of Certain Cytokine Genes and bcl-2 in Mast Cells

Bullock, E D; Johnson, Eugene M.

doi:10.1074/jbc.271.44.27500

Cited by 88 publications

(56 citation statements)

References 65 publications

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“…32 In addition, another group has also observed up-regulation of bcl-2 mRNA, but not bcl-xL mRNA, in rat peritoneal mast cells following incubation with SCF. 26 Our in vitro findings point to the possibility that activating c-kit mutations present in adult sporadic mastocytosis may be associated with bcl-2 overexpression in cutaneous mast cells. However, a similarly enhanced expression of bcl-2 was also observed in pediatric patients who fail to carry these activating mutations.…”

Section: Discussionmentioning

confidence: 82%

“…19,20,24 In vitro studies have demonstrated that survival of murine and human mast cells also depends on bcl-2 and bcl-xL. [25][26][27][28][29][30][31][32] Bcl-2-deficient mice show reduced numbers of mast cells in the stomach mucosa, although numbers of cutaneous mast cells are comparable to wild-type controls. 33 Recently, bone marrow mast cells of patients with systemic mastocytosis have been reported to strongly express bcl-xL.…”

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confidence: 99%

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Expression of Bcl-2 and Bcl-xL in Cutaneous and Bone Marrow Lesions of Mastocytosis

Hartmann

Artuc

Baldus

et al. 2003

The American Journal of Pathology

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Mastocytosis is a rare disease characterized by accumulation of mast cells in tissues.To investigate whether an altered regulation of mast cell apoptosis might be involved in the pathogenesis of mastocytosis, expression of the apoptosis-preventing molecules bcl-2 and bcl-xL was studied by immunohistochemistry in skin and bone marrow lesions of mastocytosis patients. In addition, reverse transcription-polymerase chain reaction was used to investigate levels of bcl-2 and bcl-xL mRNA in cutaneous mastocytosis lesions. Since activating mutations of c-kit are known to be associated with some forms of mastocytosis, human mast cell cultures were also stimulated via c-kit and the expression of bcl-2 and bcl-xL was assessed by immunoblotting. In patients with mastocytosis, the expression of bcl-2 protein but not bcl-xL in cutaneous mast cells was significantly enhanced, compared to healthy controls. Evaluating different subgroups of adult and pediatric mastocytosis patients, all groups were found to express significantly increased levels of bcl-2 protein, and none of the patient groups was found to overexpress bcl-xL, with the exception of solitary mastocytomas that showed a tendency for up-regulated bcl-xL protein. Furthermore, the expression of bcl-2 mRNA was significantly enhanced in cutaneous lesions of adult and pediatric patients, while bcl-xL mRNA levels were only slightly increased in pediatric, but not in adult patients with mastocytosis. In contrast to the skin lesions, bone marrow infiltrates of patients with systemic mastocy- Mastocytosis represents a heterogeneous group of diseases characterized by an increase of mast cells in different organs.

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Section: Discussionmentioning

confidence: 82%

mentioning

confidence: 99%

Expression of Bcl-2 and Bcl-xL in Cutaneous and Bone Marrow Lesions of Mastocytosis

Hartmann

Artuc

Baldus

et al. 2003

The American Journal of Pathology

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“…A total of 1 g of total RNA was reverse-transcribed into cDNA by using Moloney murine leukemia virus reverse transcriptase (Superscript II; Life Technologies) and an oligo(dT) primer. Specific primers for amplification were based on published sequences for IL-3, IL-4, IL-10, TNF-␣, IFN-␥, GM-CSF, and ␤-actin (35,36). A quantitative PCR was performed using a SYBR Green PCR core reagent kit (PE Applied Biosystems, Tokyo, Japan) following the thermal cycling programs: stage 1, 50°C for 3 min; stage 2, 95°C for 10 min; stage 3, 40 cycles of 95°C for 15 s followed by 60°C for 30 s. Fluorescence intensity was measured in real-time during extension steps for a SYBR Green assay by using a Nippon Bio-Rad thermal cycler (iCycler iQ detection system; Nippon Bio-Rad Laboratories, Tokyo, Japan).…”

Section: Real-time Pcr Quantification Of Rat Cytokinesmentioning

confidence: 99%

Nerve Growth Factor Activates Mast Cells Through the Collaborative Interaction with Lysophosphatidylserine Expressed on the Membrane Surface of Activated Platelets

Kawamoto

Aoki

Tanaka

et al. 2002

The Journal of Immunology

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Effect of nerve growth factor (NGF) on platelet-associated mast cell activation was investigated. Although neither NGF alone nor platelets alone induced significant 5-hydroxytriptamine (5-HT) release from rat peritoneal mast cells, marked 5-HT release was detected when costimulated with NGF and calcium ionophore-activated platelets. This response reached maximal levels as early as 5 min after the initiation of the coincubation and was completely blocked by anti-NGF Ab or by an inhibitor for a tyrosine kinase of the trkA NGF receptor. Paraformaldehyde-fixed platelets activated with either calcium ionophore or thrombin exhibited the collaborative ability, suggesting the possible involvement of some membrane molecules expressed on activated platelets in mast cell activation. Because activation of platelets induced expression of phosphatidylserine (PS) and/or lysoPS on membrane surface, and since lysoPS, unlike PS, initiated the NGF-induced 5-HT release, lysoPS expressed on activated platelets may be involved in the mast cell activation. Moreover, intradermal injection of NGF and activated platelets into the rat skin increased local vascular permeability. These findings suggested that NGF collaboratively worked with membrane lysoPS of activated platelets to induce mast cell activation. Thus, NGF released in response to inflammatory stimuli may contribute to mast cell activation in collaboration with locally activated platelets in the process of inflammations and tissue repair.

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“…NGF also has a profound effect on cells of the immune system, many of which are critically important in the development of pulmonary inflammation and asthma-related symptoms. Hence, NGF increases the number of mast cells in peripheral tissue [6] and promotes mast cell differentiation [7] and survival [8]. In addition, NGF stimulates lymphocyte survival, proliferation and differentiation, and it enhances eosinophil survival and cytotoxicity [9].…”

mentioning

confidence: 99%

Human lung fibroblasts secrete nerve growth factor: effect of inflammatory cytokines and glucocorticoids

2001

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Human lung fibroblasts secrete nerve growth factor: effect of inflammatory cytokines and glucocorticoids. C. Olgart, N. Frossard. #ERS Journals Ltd 2001. ABSTRACT: Nerve growth factor (NGF) has recently been suggested to contribute to inflammation and bronchial hyperresponsiveness in asthma. However, the cell types capable of NGF production in the human lung and airways, as well as the regulatory role of pro-inflammatory cytokines and of glucocorticoids on NGF secretion in pulmonary cells, have not been described.Human pulmonary fibroblasts were cultured in the presence or absence of either interleukin-1b (IL-1b), tumour necrosis factor-a (TNF-a) and/or glucocorticoids. NGF secretion was measured by enzyme-linked immunosorbent assay.The human pulmonary fibroblasts constitutively secreted NGF in vitro. The rate of NGF secretion was shown to be cell density-dependent, since higher NGF secretion was detected in preconfluent cells, i.e. ones with less established cell-to-cell contact (41.0¡5.0 pg?10 -6 cells at 80% confluence), than cells in higher densities (8.2¡3.4 pg?10 -6 cells at 100% confluence). Stimulation with the pro-inflammatory cytokines IL-1b (0.3 -30 U?mL -1 ) or TNF-a (0.1 -30 ng?mL -1 ) dose-and timedependently (8 -72 h) elevated the NGF secretion (effective concentration causing 50% of the maximum response (EC50)~2.9 U?mL -1 and 1.0 ng?mL -1 , respectively). Treatment with the glucocorticoid budesonide (10 -7 M) markedly reduced the constitutive secretion of NGF by 42%, and attenuated the cytokine-stimulated NGF secretion to the same level.In conclusion, human lung fibroblasts may serve as a source of nerve growth factor in the lung, positively regulated by the asthma-associated and pro-inflammatory cytokines interleukin-1b and tumour necrosis factor-a, and negatively regulated by the antiinflammatory glucocorticoids.

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Nerve Growth Factor Induces the Expression of Certain Cytokine Genes and bcl-2 in Mast Cells

Cited by 88 publications

References 65 publications

Expression of Bcl-2 and Bcl-xL in Cutaneous and Bone Marrow Lesions of Mastocytosis

Expression of Bcl-2 and Bcl-xL in Cutaneous and Bone Marrow Lesions of Mastocytosis

Nerve Growth Factor Activates Mast Cells Through the Collaborative Interaction with Lysophosphatidylserine Expressed on the Membrane Surface of Activated Platelets

Human lung fibroblasts secrete nerve growth factor: effect of inflammatory cytokines and glucocorticoids

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