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Michael A. Beaven - One of the best experts on this subject based on the ideXlab platform.
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Enhancement of TNF-alpha synthesis by overexpression of G alpha z in a Mast Cell Line.
Journal of immunology (Baltimore Md. : 1950), 1996Co-Authors: Rudolf A. Baumgartner, N Hirasawa, K Ozawa, F Gusovsky, Michael A. BeavenAbstract:Ag stimulation of Mast Cells via the IgE receptor (Fc epsilon RI) elicits production and release of numerous cytokines. This activation of Fc epsilon RI initiates various tyrosine kinase-dependent signaling cascades, which ultimately result in the de novo synthesis of cytokines. To date, no heterotrimeric G proteins have been implicated in this process. Here we report that the alpha subunit of the heterotrimeric G protein, Gz, can regulate production of the cytokine, TNF-alpha. The alpha subunit was overexpressed in a cultured Mast Cell Line (RBL-2H3) known to contain G alpha z. In stimulated Cells, overexpression of G alpha z significantly enhanced the production of TNF-alpha. This effect of G alpha z appeared to be restricted in that constitutive synthesis of the cytokine, TGF-beta, and Ag-stimulation of the phosphoinositide-dependent secretory pathway were not significantly affected. Thus, G alpha z, a heterotrimeric G protein, appeared to modulate the stimulatory pathways for induction of TNF-alpha synthesis in RBL-2H3 Cells.
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Carbachol induces secretion in a Mast Cell Line (RBL‐2H3) transfected with the ml muscarinic receptor gene
FEBS Letters, 1991Co-Authors: S.v.penelope Jones, Oksoon H. Choi, Michael A. BeavenAbstract:The possibility that the ml muscarinic receptor subtype can induce release of intraCellular granules and transmitters was studied by transfecting a cultured Mast Cell Line, RBL-2H3 Cells, with the ml receptor gene. Comparisons were made between carbachol- and antigen-induced activation of various secretory responses. Like antigen, carbachol stimulated inositol phospholipid hydrolysis and release of arachidonic acid with concomitant dose-dependent secretion of granular contents. Carbachol also stimulated a biphasic increase in intraCellular calcium, as measured by single Cell fura-2 measurements. Although the kinetics of the carbachol-induced rise in intraCellular calcium differed from that induced by antigen, they both utilized the same intraCellular pool of calcium, and the second phase of the rise in intraCellular calcium was dependent on extraCellular calcium in both cases. Thus, the ml muscarinic receptor activates release of granules by a mechanism ostensibly similar to that of antigen.
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carbachol induces secretion in a Mast Cell Line rbl 2h3 transfected with the ml muscarinic receptor gene
FEBS Letters, 1991Co-Authors: S Penelope V Jones, Oksoon H. Choi, Michael A. BeavenAbstract:The possibility that the ml muscarinic receptor subtype can induce release of intraCellular granules and transmitters was studied by transfecting a cultured Mast Cell Line, RBL-2H3 Cells, with the ml receptor gene. Comparisons were made between carbachol- and antigen-induced activation of various secretory responses. Like antigen, carbachol stimulated inositol phospholipid hydrolysis and release of arachidonic acid with concomitant dose-dependent secretion of granular contents. Carbachol also stimulated a biphasic increase in intraCellular calcium, as measured by single Cell fura-2 measurements. Although the kinetics of the carbachol-induced rise in intraCellular calcium differed from that induced by antigen, they both utilized the same intraCellular pool of calcium, and the second phase of the rise in intraCellular calcium was dependent on extraCellular calcium in both cases. Thus, the ml muscarinic receptor activates release of granules by a mechanism ostensibly similar to that of antigen.
Joseph H. Butterfield - One of the best experts on this subject based on the ideXlab platform.
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Functional and phenotypic studies of two variants of a human Mast Cell Line with a distinct set of mutations in the c-kit proto-oncogene
Immunology, 2003Co-Authors: Magnus Sundström, Joseph H. Butterfield, Dean D. Metcalfe, Harissios Vliagoftis, Peter Karlberg, Kenneth Nilsson, Gunnar NilssonAbstract:Functional and phenotypic studies of two variants of a human Mast Cell Line with a distinct set ofmutations in the c-kit proto-oncogene
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The HMC-1 human Mast Cell Line expresses the hepatocyte growth factor receptor c-met.
Biochemical and Biophysical Research Communications, 1997Co-Authors: Koji Yano, Joseph H. Butterfield, Kazuhiko Nakao, Koichi Sayama, Keisuke Hamasaki, Yuji Kato, Keisuke Nakata, Nobuko Ishii, Stephen J. GalliAbstract:Abstract Hepatocyte growth factor (HGF) was originally characterized as a strong inducer of liver regeneration. However, it is now clear that HGF and its receptor, the proto-oncogene c-met, can be expressed in many other tissues, and that HGF can mediate diverse biological activities. We investigated the expression and function of c-met in a human Mast Cell Line (HMC-1). We found that HMC-1 Cells express c-met and that c-met expression can be upregulated by treatment of the Cells with phorbol 12-myristate 13-acetate (PMA). Although HGF did not detectably influence the proliferation or morphology of HMC-1 Cells, HGF inhibited the Cells’ ability to release tumor necrosis factor-alpha (TNF-α) in response to stimulation with PMA and the calcium ionophore, A23187. These results add the inhibition of TNF-α production to the other recognized effects of HGF/c-met on Cellular function.
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The Human Mast Cell Line HMC‐1 Expresses C5a Receptors and Responds to C5a but not to C5a(desArg)
Scandinavian Journal of Immunology, 1996Co-Authors: Thomas Werfel, Joseph H. Butterfield, Martin Oppermann, G. Begemann, J. Elsner, Otto Götze, Jörg ZwirnerAbstract:The expression of the receptor for the anaphylatoxin C5a (C5aR, CD88) on the human Mast Cell Line HMC-1 was studied with four anti-C5aR monoclonal antibodies directed to the N-terminal domain of the receptor. All antibodies bound to the human Mast Cell Line HMC-1. The binding could be blocked by recombinant C5a and by peptide EX-1 representing amino residues 1-31 on the N-terminal domain of the C5aR. In addition, FITC-labelled C5a bound to HMC-1, and this binding could be blocked by unlabelled C5a or C5aR antibodies. C5aR-specific mRNA was detected in HMC-1 Cells by RT-PCR which confirmed the expression of the C5aR gene made by these Cells. Lymphocyte-conditioned medium, interferon-gamma or phorbol esters which have been shown to induce a down-regulation of C5aR on myeloid Cells did not influence the expression of C5aR on HMC-1. C5a led to a transient mobilization of intraCellular calcium in HMC-1 which could be inhibited by pre incubation of C5a with a C5a-specific antibody. In contrast to findings with granulocytes, HMC-1 did not respond to C5a(desArg), confirming previous findings with human skin Mast Cells. The findings show that (i) although HMC-1 differ from granulocytes in their responsiveness to C5a(desArg), they express similar C5aR and (ii) HMC-1 Cells resemble skin Mast Cells in the expression and function of C5aR and may therefore serve as a model in future studies addressing the biology of this anaphylatoxin receptor on skin Mast Cells.
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Specific inhibition of beta-tryptase expression in a human Mast Cell Line by granulocyte-macrophage colony-stimulating factor produced by airways structural Cells.
American Journal of Respiratory Cell and Molecular Biology, 1996Co-Authors: Susetta Finotto, Joseph H. Butterfield, Jean S. Marshall, Judah A. DenburgAbstract:The growth and differentiation of Mast Cells are regulated by cytokines produced in tissue microenvironments. We previously reported that Mast Cells isolated from the epithelial compartment of nasal polyp tissue contain significantly less tryptase when compared with Mast Cells isolated from the stroma of the same tissue. In an attempt to explore this finding, we analyzed the ability of supernatants obtained from cultured nasal polyp epithelial Cells (NP-EpCM) or nasal polyp fibroblasts (NP-FbCM) to regulate the tryptase content of the immature human Mast Cell Line HMC-1. HMC-1 Cells were cultured for 7 days in Iscove's modified Dulbecco's medium (IMDM) with 30% of either NP-FbCM or NP-EpCM or 20% MoCM (supernatant of a leukemic T Cell Line). As assessed by radioimmunoassay and test for enzymatic activity, all three conditioned media were shown to significantly decrease tryptase protein expression in HMC-1, when compared with cultures performed with IMDM alone (NP-EpCM P < 0.001; NP-FbCM P < 0.04; MoCM P
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IFN-γ-Stimulated Enhancement of MHC Class II Antigen Expression by the Human Mast Cell Line HMC-1
Cellular Immunology, 1996Co-Authors: Kelley S. Love, Joseph H. Butterfield, Romola R. Lakshmanan, Charity C. FoxAbstract:Abstract The expression of MHC class II molecules by human Mast Cells has been reported in immunohistochemical surveys of inflammatory conditions, such as in tuberculin hypersensitivity. While these data suggest that human Mast Cells may act as antigen-presenting Cells under inflammatory conditions, the induction of class II antigens on human Mast Cells has not been examined. In this study, we determined the effects of the inflammatory cytokines IFN-γ and IL-4 on the expression of class II antigens HLA-DR, -DP, and -DQ by the human Mast Cell Line HMC-1. HMC-1 Cells were incubated with or without 1000 U/ml recombinant human IFN-γ (rhIFN-γ) and IL-4 (rhIL-4) for 72 hr and analyzed for expression of MHC class II antigens by direct immunofluorescence and flow cytometry. HMC-1 Cells expressed significant levels of HLA-DR and moderate levels of HLA-DP and -DQ at baseLine and when cultured without exogenous cytokines. Stimulation by rhIFN-γ for 72 hr significantly increased the levels of HLA-DR and -DP expression but did not affect levels of HLA-DQ. Stimulation by rhIL-4 for 72 hr had minimal effect on expression of class II molecules, but induced a significant difference in levels of ICAM-1 (CD54) expression, indicating that this cytokine is involved instead in the control of certain accessory molecules. Our data showing constitutive expression of MHC class II molecules on HMC-1 Cells and upregulation of that expression by rhIFN-γ suggest that human Mast Cells function as antigen-presenting Cells at sites where inflammatory cytokines are present.
Rudolf A. Baumgartner - One of the best experts on this subject based on the ideXlab platform.
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Enhancement of TNF-alpha synthesis by overexpression of G alpha z in a Mast Cell Line.
Journal of immunology (Baltimore Md. : 1950), 1996Co-Authors: Rudolf A. Baumgartner, N Hirasawa, K Ozawa, F Gusovsky, Michael A. BeavenAbstract:Ag stimulation of Mast Cells via the IgE receptor (Fc epsilon RI) elicits production and release of numerous cytokines. This activation of Fc epsilon RI initiates various tyrosine kinase-dependent signaling cascades, which ultimately result in the de novo synthesis of cytokines. To date, no heterotrimeric G proteins have been implicated in this process. Here we report that the alpha subunit of the heterotrimeric G protein, Gz, can regulate production of the cytokine, TNF-alpha. The alpha subunit was overexpressed in a cultured Mast Cell Line (RBL-2H3) known to contain G alpha z. In stimulated Cells, overexpression of G alpha z significantly enhanced the production of TNF-alpha. This effect of G alpha z appeared to be restricted in that constitutive synthesis of the cytokine, TGF-beta, and Ag-stimulation of the phosphoinositide-dependent secretory pathway were not significantly affected. Thus, G alpha z, a heterotrimeric G protein, appeared to modulate the stimulatory pathways for induction of TNF-alpha synthesis in RBL-2H3 Cells.
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Secretion of TNF from a rat Mast Cell Line is a brefeldin A-sensitive and a calcium/protein kinase C-regulated process.
Journal of immunology (Baltimore Md. : 1950), 1994Co-Authors: Rudolf A. Baumgartner, Koji Yamada, V A Deramo, M A BeavenAbstract:Stimulated Mast Cells and cognate cultured Cell Lines produce and secrete a variety of cytokines including TNF. Because the mechanism by which cytokines are delivered to the external milieu is unknown, the release of TNF was studied in a rat Mast Cell Line (RBL-2H3 Cells). In these Cells, TNF was not constitutively expressed nor incorporated into secretory granules but was generated de novo upon Cell stimulation. It was then released by a process analogous to constitutive secretion in that brefeldin A, an agent known to disrupt Golgi membranes in these Cells, inhibited this release without inhibiting release of secretory granules. Unlike constitutive secretion, however, the secretion of TNF was highly regulated by Ca2+ and protein kinase C. Studies with various stimulants and inhibitors indicated that simultaneous mobilization of Ca2+ and activation of protein kinase C were sufficient signals for secretion although optimal production of TNF may be dependent on additional synergistic signals. Because suppression of Ca2+ mobilization or inhibition of protein kinase C alone abrogated TNF secretion, the process may be amenable to therapeutic intervention.
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secretion of tnf from a rat Mast Cell Line is a brefeldin a sensitive and a calcium protein kinase c regulated process
Journal of Immunology, 1994Co-Authors: Rudolf A. Baumgartner, Koji Yamada, V A Deramo, M A BeavenAbstract:Stimulated Mast Cells and cognate cultured Cell Lines produce and secrete a variety of cytokines including TNF. Because the mechanism by which cytokines are delivered to the external milieu is unknown, the release of TNF was studied in a rat Mast Cell Line (RBL-2H3 Cells). In these Cells, TNF was not constitutively expressed nor incorporated into secretory granules but was generated de novo upon Cell stimulation. It was then released by a process analogous to constitutive secretion in that brefeldin A, an agent known to disrupt Golgi membranes in these Cells, inhibited this release without inhibiting release of secretory granules. Unlike constitutive secretion, however, the secretion of TNF was highly regulated by Ca2+ and protein kinase C. Studies with various stimulants and inhibitors indicated that simultaneous mobilization of Ca2+ and activation of protein kinase C were sufficient signals for secretion although optimal production of TNF may be dependent on additional synergistic signals. Because suppression of Ca2+ mobilization or inhibition of protein kinase C alone abrogated TNF secretion, the process may be amenable to therapeutic intervention.
Chun-kwok Wong - One of the best experts on this subject based on the ideXlab platform.
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molecular mechanisms for the release of chemokines from human leukemic Mast Cell Line hmc 1 Cells activated by scf and tnf alpha roles of erk p38 mapk and nf kappab
Allergy, 2006Co-Authors: Chun-kwok Wong, Chi-man Tsang, W K IpAbstract:BACKGROUND: Mast Cells play pivotal roles in IgE-mediated airway inflammation and other Mast Cell-mediated inflammation by activation and chemoattraction of inflammatory Cells. OBJECTIVE: We investigated the intraCellular signaling mechanisms regulating chemokine release from human Mast Cell Line-1 (HMC-1) Cells activated by stem Cell factor (SCF) or tumor necrosis factor (TNF)-alpha. METHODS: Chemokine gene expressions were assessed by reverse transcription-polymerase chain reaction, while the releases of chemokines were determined by flow cytometry or enzyme-linked immunosorbent assay (ELISA). To elucidate the intraCellular signal transduction regulating the chemokine expression, phosphorylated-extraCellular signal-regulated kinase (ERK), phosphorylated-p38 mitogen-activated protein kinase (MAPK) and nuclear translocated nuclear factor (NF)-kappaB-DNA binding were quantitatively assessed by ELISA. RESULTS: Either SCF or TNF-alpha could induce release from HMC-1 Cells of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, regulated upon activation normal T-Cell expressed and secreted (RANTES), and I-309, while SCF and TNF-alpha induced release of macrophage inflammatory protein (MIP)-1beta and interferon-gamma-inducible protein-10 (IP-10), respectively. Using various selective inhibitors for signaling molecules, we found that the inductions of IL-8, MCP-1, and I-309 were mediated by either SCF-activated ERK or TNF-alpha-activated p38 MAPK, while the induction of IP-10 by TNF-alpha was mediated by both activated p38 MAPK and NF-kappaB. The induction of RANTES by SCF or TNF-alpha was mediated by ERK and NF-kappaB, respectively, and SCF induced MIP-1beta release was mediated by ERK. CONCLUSION: The above results therefore elucidated the different intraCellular signaling pathways regulating the release of different chemokines from SCF and TNF-alpha-activated Mast Cells, thereby shedding light for the immunopathological mechanisms of Mast Cell-mediated diseases.
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synergistic effect of scf and tnf α on the up regulation of Cell surface expression of icam 1 on human leukemic Mast Cell Line hmc 1 Cells
Journal of Leukocyte Biology, 2005Co-Authors: Chi-man Tsang, Chun-kwok Wong, Christopher W.k. LamAbstract:InterCellular adhesion molecule-1 (ICAM-1) has been shown to play crucial roles in Mast Cell interaction with other inflammatory Cells and recruitment into the inflamed tissue. In the present study, human Mast Cell Line-1 (HMC-1) was stimulated with different cytokines including stem Cell factor (SCF), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-13, IL-18, and IL-25. Cell-surface expression of ICAM-1 was assessed by flow cytometry. To elucidate the intraCellular signal transduction regulating the ICAM-1 expression, phosphorylated extraCellular signal-regulated kinase (ERK), phosphorylated p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-kappaB translocation were assessed by enzyme-linked immunosorbent assay. Results showed that SCF, TNF-alpha, and IL-13 but not IL-18 and IL-25 could up-regulate the surface expression of ICAM-1 on HMC-1 Cells. A synergistic effect of SCF and TNF-alpha on ICAM-1 expression was demonstrated. This synergistic effect was shown to be dose-dependently enhanced by SCF but not TNF-alpha. Results indicated that SCF activated ERK, and TNF-alpha activated the p38 MAPK and NF-kappaB pathway. Selective inhibitor of ERK, PD098059, and c-kit inhibitors, STI571 and PP1, suppressed the combined SCF and TNF-alpha-induced ICAM-1 expression. BAY117082 but not SB203580, which are the inhibitors of NF-kappaB and p38 MAPK, respectively, suppressed the TNF-alpha-induced ICAM-1 expression. Therefore, SCF and TNF-alpha acted through ERK and the NF-kappaB pathway to regulate the ICAM-1 expression and elicited the synergistic effect. In conclusion, our results provide insight for cross-talk between different signaling pathways that can help in understanding the fine control of adhesion molecule expression under the concerted effects of cytokines.
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Synergistic effect of SCF and TNF‐α on the up‐regulation of Cell‐surface expression of ICAM‐1 on human leukemic Mast Cell Line (HMC)‐1 Cells
Journal of Leukocyte Biology, 2005Co-Authors: Chi-man Tsang, Chun-kwok Wong, Christopher W.k. LamAbstract:InterCellular adhesion molecule-1 (ICAM-1) has been shown to play crucial roles in Mast Cell interaction with other inflammatory Cells and recruitment into the inflamed tissue. In the present study, human Mast Cell Line-1 (HMC-1) was stimulated with different cytokines including stem Cell factor (SCF), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-13, IL-18, and IL-25. Cell-surface expression of ICAM-1 was assessed by flow cytometry. To elucidate the intraCellular signal transduction regulating the ICAM-1 expression, phosphorylated extraCellular signal-regulated kinase (ERK), phosphorylated p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-kappaB translocation were assessed by enzyme-linked immunosorbent assay. Results showed that SCF, TNF-alpha, and IL-13 but not IL-18 and IL-25 could up-regulate the surface expression of ICAM-1 on HMC-1 Cells. A synergistic effect of SCF and TNF-alpha on ICAM-1 expression was demonstrated. This synergistic effect was shown to be dose-dependently enhanced by SCF but not TNF-alpha. Results indicated that SCF activated ERK, and TNF-alpha activated the p38 MAPK and NF-kappaB pathway. Selective inhibitor of ERK, PD098059, and c-kit inhibitors, STI571 and PP1, suppressed the combined SCF and TNF-alpha-induced ICAM-1 expression. BAY117082 but not SB203580, which are the inhibitors of NF-kappaB and p38 MAPK, respectively, suppressed the TNF-alpha-induced ICAM-1 expression. Therefore, SCF and TNF-alpha acted through ERK and the NF-kappaB pathway to regulate the ICAM-1 expression and elicited the synergistic effect. In conclusion, our results provide insight for cross-talk between different signaling pathways that can help in understanding the fine control of adhesion molecule expression under the concerted effects of cytokines.
Chi-man Tsang - One of the best experts on this subject based on the ideXlab platform.
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molecular mechanisms for the release of chemokines from human leukemic Mast Cell Line hmc 1 Cells activated by scf and tnf alpha roles of erk p38 mapk and nf kappab
Allergy, 2006Co-Authors: Chun-kwok Wong, Chi-man Tsang, W K IpAbstract:BACKGROUND: Mast Cells play pivotal roles in IgE-mediated airway inflammation and other Mast Cell-mediated inflammation by activation and chemoattraction of inflammatory Cells. OBJECTIVE: We investigated the intraCellular signaling mechanisms regulating chemokine release from human Mast Cell Line-1 (HMC-1) Cells activated by stem Cell factor (SCF) or tumor necrosis factor (TNF)-alpha. METHODS: Chemokine gene expressions were assessed by reverse transcription-polymerase chain reaction, while the releases of chemokines were determined by flow cytometry or enzyme-linked immunosorbent assay (ELISA). To elucidate the intraCellular signal transduction regulating the chemokine expression, phosphorylated-extraCellular signal-regulated kinase (ERK), phosphorylated-p38 mitogen-activated protein kinase (MAPK) and nuclear translocated nuclear factor (NF)-kappaB-DNA binding were quantitatively assessed by ELISA. RESULTS: Either SCF or TNF-alpha could induce release from HMC-1 Cells of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, regulated upon activation normal T-Cell expressed and secreted (RANTES), and I-309, while SCF and TNF-alpha induced release of macrophage inflammatory protein (MIP)-1beta and interferon-gamma-inducible protein-10 (IP-10), respectively. Using various selective inhibitors for signaling molecules, we found that the inductions of IL-8, MCP-1, and I-309 were mediated by either SCF-activated ERK or TNF-alpha-activated p38 MAPK, while the induction of IP-10 by TNF-alpha was mediated by both activated p38 MAPK and NF-kappaB. The induction of RANTES by SCF or TNF-alpha was mediated by ERK and NF-kappaB, respectively, and SCF induced MIP-1beta release was mediated by ERK. CONCLUSION: The above results therefore elucidated the different intraCellular signaling pathways regulating the release of different chemokines from SCF and TNF-alpha-activated Mast Cells, thereby shedding light for the immunopathological mechanisms of Mast Cell-mediated diseases.
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synergistic effect of scf and tnf α on the up regulation of Cell surface expression of icam 1 on human leukemic Mast Cell Line hmc 1 Cells
Journal of Leukocyte Biology, 2005Co-Authors: Chi-man Tsang, Chun-kwok Wong, Christopher W.k. LamAbstract:InterCellular adhesion molecule-1 (ICAM-1) has been shown to play crucial roles in Mast Cell interaction with other inflammatory Cells and recruitment into the inflamed tissue. In the present study, human Mast Cell Line-1 (HMC-1) was stimulated with different cytokines including stem Cell factor (SCF), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-13, IL-18, and IL-25. Cell-surface expression of ICAM-1 was assessed by flow cytometry. To elucidate the intraCellular signal transduction regulating the ICAM-1 expression, phosphorylated extraCellular signal-regulated kinase (ERK), phosphorylated p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-kappaB translocation were assessed by enzyme-linked immunosorbent assay. Results showed that SCF, TNF-alpha, and IL-13 but not IL-18 and IL-25 could up-regulate the surface expression of ICAM-1 on HMC-1 Cells. A synergistic effect of SCF and TNF-alpha on ICAM-1 expression was demonstrated. This synergistic effect was shown to be dose-dependently enhanced by SCF but not TNF-alpha. Results indicated that SCF activated ERK, and TNF-alpha activated the p38 MAPK and NF-kappaB pathway. Selective inhibitor of ERK, PD098059, and c-kit inhibitors, STI571 and PP1, suppressed the combined SCF and TNF-alpha-induced ICAM-1 expression. BAY117082 but not SB203580, which are the inhibitors of NF-kappaB and p38 MAPK, respectively, suppressed the TNF-alpha-induced ICAM-1 expression. Therefore, SCF and TNF-alpha acted through ERK and the NF-kappaB pathway to regulate the ICAM-1 expression and elicited the synergistic effect. In conclusion, our results provide insight for cross-talk between different signaling pathways that can help in understanding the fine control of adhesion molecule expression under the concerted effects of cytokines.
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Synergistic effect of SCF and TNF‐α on the up‐regulation of Cell‐surface expression of ICAM‐1 on human leukemic Mast Cell Line (HMC)‐1 Cells
Journal of Leukocyte Biology, 2005Co-Authors: Chi-man Tsang, Chun-kwok Wong, Christopher W.k. LamAbstract:InterCellular adhesion molecule-1 (ICAM-1) has been shown to play crucial roles in Mast Cell interaction with other inflammatory Cells and recruitment into the inflamed tissue. In the present study, human Mast Cell Line-1 (HMC-1) was stimulated with different cytokines including stem Cell factor (SCF), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-13, IL-18, and IL-25. Cell-surface expression of ICAM-1 was assessed by flow cytometry. To elucidate the intraCellular signal transduction regulating the ICAM-1 expression, phosphorylated extraCellular signal-regulated kinase (ERK), phosphorylated p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-kappaB translocation were assessed by enzyme-linked immunosorbent assay. Results showed that SCF, TNF-alpha, and IL-13 but not IL-18 and IL-25 could up-regulate the surface expression of ICAM-1 on HMC-1 Cells. A synergistic effect of SCF and TNF-alpha on ICAM-1 expression was demonstrated. This synergistic effect was shown to be dose-dependently enhanced by SCF but not TNF-alpha. Results indicated that SCF activated ERK, and TNF-alpha activated the p38 MAPK and NF-kappaB pathway. Selective inhibitor of ERK, PD098059, and c-kit inhibitors, STI571 and PP1, suppressed the combined SCF and TNF-alpha-induced ICAM-1 expression. BAY117082 but not SB203580, which are the inhibitors of NF-kappaB and p38 MAPK, respectively, suppressed the TNF-alpha-induced ICAM-1 expression. Therefore, SCF and TNF-alpha acted through ERK and the NF-kappaB pathway to regulate the ICAM-1 expression and elicited the synergistic effect. In conclusion, our results provide insight for cross-talk between different signaling pathways that can help in understanding the fine control of adhesion molecule expression under the concerted effects of cytokines.