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Allergy 2006, PMID: 16436136

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.

Wong, C K; Tsang, C M; Ip, W K; Lam, C W K

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.

CONCLUSIONS

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.

Document information provided by NCBI PubMed

Text Mining Data

interferon-gamma-inducible protein-10 (IP-10) → TNF-alpha: " 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 "

interferon-gamma-inducible protein-10 (IP-10) → SCF: " 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 "

SCF → interferon-gamma-inducible protein-10 (IP-10): " 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 "

SCF → TNF-alpha: " 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 "

SCF → (MIP)-1beta: " 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 "

SCF → interferon-gamma-inducible: " 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 "

SCF → SCF: " 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 "

SCF → macrophage inflammatory protein (MIP)-1beta: " 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 "

TNF-alpha → (MIP)-1beta: " 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 "

TNF-alpha → interferon-gamma-inducible: " 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 "

TNF-alpha → SCF: " 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 "

TNF-alpha → macrophage inflammatory protein (MIP)-1beta: " 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 "

(MIP)-1beta → SCF: " 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 "

interferon-gamma-inducible → SCF: " 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 "

SCF → macrophage inflammatory protein (MIP)-1beta: " 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 "

MCP-1 → ERK: " 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 "

MCP-1 → p38: " 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 "

IP-10 → TNF-alpha: " 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 "

IP-10 → MAPK: " 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 "

IP-10 → NF-kappaB: " 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 "

IL-8 → ERK: " 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 "

IL-8 → p38: " 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 "

MCP-1 → ERK: " 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 "

MCP-1 → p38: " 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 "

MIP-1beta → SCF: " 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 "

MIP-1beta → TNF-alpha: " 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 "

MIP-1beta → ERK: " 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 "

MIP-1beta → 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 "

SCF → TNF-alpha: " 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 "

SCF → ERK: " 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 "

SCF → 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 "

Manually curated Databases

No curated data.