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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. 2006 Mar; 61(3):289-97.A

Abstract

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.

Authors+Show Affiliations

Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16436136

Citation

Wong, C K., et al. "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, vol. 61, no. 3, 2006, pp. 289-97.
Wong CK, Tsang CM, Ip WK, et al. 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. 2006;61(3):289-97.
Wong, C. K., Tsang, C. M., Ip, W. K., & Lam, C. W. (2006). 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, 61(3), 289-97.
Wong CK, et al. 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. 2006;61(3):289-97. PubMed PMID: 16436136.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Wong,C K, AU - Tsang,C M, AU - Ip,W K, AU - Lam,C W K, PY - 2006/1/27/pubmed PY - 2006/7/11/medline PY - 2006/1/27/entrez SP - 289 EP - 97 JF - Allergy JO - Allergy VL - 61 IS - 3 N2 - 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. SN - 0105-4538 UR - https://www.unboundmedicine.com/medline/citation/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_ L2 - https://doi.org/10.1111/j.1398-9995.2006.00972.x DB - PRIME DP - Unbound Medicine ER -