Premium
Molecular mechanisms for the release of chemokines from human leukemic mast cell line (HMC)‐1 cells activated by SCF and TNF‐ α : roles of ERK, p38 MAPK, and NF‐ κ B
Author(s) -
Wong C. K.,
Tsang C. M.,
Ip W. K.,
Lam C. W. K.
Publication year - 2006
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2006.00972.x
Subject(s) - chemokine , mapk/erk pathway , microbiology and biotechnology , p38 mitogen activated protein kinases , protein kinase a , tumor necrosis factor alpha , signal transduction , mast cell , biology , monocyte , macrophage inflammatory protein , cytokine , kinase , chemistry , inflammation , immunology
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)‐ α . 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)‐ κ B‐DNA binding were quantitatively assessed by ELISA. Results: Either SCF or TNF‐ α 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‐ α induced release of macrophage inflammatory protein (MIP)‐1 β and interferon‐ γ ‐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‐ α ‐activated p38 MAPK, while the induction of IP‐10 by TNF‐ α was mediated by both activated p38 MAPK and NF‐ κ B. The induction of RANTES by SCF or TNF‐ α was mediated by ERK and NF‐ κ B, respectively, and SCF induced MIP‐1 β 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‐ α ‐activated mast cells, thereby shedding light for the immunopathological mechanisms of mast cell‐mediated diseases.