p38 MAP kinase regulates TNFα-, IL-1α- and PAF-induced RANTES and GM-CSF production by human bronchial epithelial cells
Background RANTES and granulocyte macrophage‐colony stimulating factor (GM‐CSF) play an important role in the production of allergic inflammation of the airway through their chemotactic activity for eosinophils. Recent studies have indicated that p38 mitogen‐activated protein (MAP) kinase regulates...
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Published in | Clinical and experimental allergy Vol. 30; no. 1; pp. 48 - 55 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford BSL
Blackwell Science Ltd
01.01.2000
Blackwell |
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Abstract | Background
RANTES and granulocyte macrophage‐colony stimulating factor (GM‐CSF) play an important role in the production of allergic inflammation of the airway through their chemotactic activity for eosinophils. Recent studies have indicated that p38 mitogen‐activated protein (MAP) kinase regulates cytokine expression in various cells; however, the role of p38 MAP kinase in RANTES and GM‐CSF production in human bronchial epithelial cells (BECs) has not yet been determined.
Objective
In the present study, we examined serine phosphorylation of MKK3 and MKK6 which is the upstream regulator of p38 MAP kinase and p38 MAP kinase activation in tumour necrosis factor (TNF)‐α, interleukin (IL)‐1α and platelet‐activating factor (PAF)‐stimulated BECs and the effect of SB 203580 as the specific inhibitor for p38 MAP kinase activity on RANTES and GM‐CSF expression in order to clarify the intracellular signal regulating RANTES and GM‐CSF production by human BECs.
Results
The results showed that TNFα, IL‐1α and PAF induced serine phosphorylation of MKK3 and MKK6, and p38 MAP kinase activation in BECs. SB 203580 inhibited p38 MAP kinase activity and RANTES and GM‐CSF production by TNFα‐, IL‐1α‐ or PAF‐stimulated human BECs.
Conclusions
These results indicate that p38 MAP kinase plays an important role in TNFα‐, IL‐1α‐ or PAF‐activated signalling pathway which regulates RANTES and GM‐CSF production by BECs and that the specific inhibitor for p38 MAP kinase activity might be useful for the treatment of allergic inflammation of the airway. |
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AbstractList | RANTES and granulocyte macrophage-colony stimulating factor (GM-CSF) play an important role in the production of allergic inflammation of the airway through their chemotactic activity for eosinophils. Recent studies have indicated that p38 mitogen-activated protein (MAP) kinase regulates cytokine expression in various cells; however, the role of p38 MAP kinase in RANTES and GM-CSF production in human bronchial epithelial cells (BECs) has not yet been determined.
In the present study, we examined serine phosphorylation of MKK3 and MKK6 which is the upstream regulator of p38 MAP kinase and p38 MAP kinase activation in tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha and platelet-activating factor (PAF)-stimulated BECs and the effect of SB 203580 as the specific inhibitor for p38 MAP kinase activity on RANTES and GM-CSF expression in order to clarify the intracellular signal regulating RANTES and GM-CSF production by human BECs.
The results showed that TNF alpha, IL-1 alpha and PAF induced serine phosphorylation of MKK3 and MKK6, and p38 MAP kinase activation in BECs. SB 203580 inhibited p38 MAP kinase activity and RANTES and GM-CSF production by TNF alpha-, IL-1 alpha- or PAF-stimulated human BECs.
These results indicate that p38 MAP kinase plays an important role in TNF alpha-, IL-1 alpha- or PAF-activated signalling pathway which regulates RANTES and GM-CSF production by BECs and that the specific inhibitor for p38 MAP kinase activity might be useful for the treatment of allergic inflammation of the airway. RANTES and granulocyte macrophage-colony stimulating factor (GM-CSF) play an important role in the production of allergic inflammation of the airway through their chemotactic activity for eosinophils. Recent studies have indicated that p38 mitogen-activated protein (MAP) kinase regulates cytokine expression in various cells; however, the role of p38 MAP kinase in RANTES and GM-CSF production in human bronchial epithelial cells (BECs) has not yet been determined. In the present study, we examined serine phosphorylation of MKK3 and MKK6 which is the upstream regulator of p38 MAP kinase and p38 MAP kinase activation in tumour necrosis factor (TNF)- alpha , interleukin (IL)-1 alpha and platelet-activating factor (PAF)-stimulated BECs and the effect of SB 203580 as the specific inhibitor for p38 MAP kinase activity on RANTES and GM-CSF expression in order to clarify the intracellular signal regulating RANTES and GM-CSF production by human BECs. The results showed that TNF alpha , IL-1 alpha and PAF induced serine phosphorylation of MKK3 and MKK6, and p38 MAP kinase activation in BECs. SB 203580 inhibited p38 MAP kinase activity and RANTES and GM-CSF production by TNF alpha -, IL-1 alpha - or PAF-stimulated human BECs. These results indicate that p38 MAP kinase plays an important role in TNF alpha -, IL-1 alpha - or PAF-activated signalling pathway which regulates RANTES and GM-CSF production by BECs and that the specific inhibitor for p38 MAP kinase activity might be useful for the treatment of allergic inflammation of the airway. Background RANTES and granulocyte macrophage‐colony stimulating factor (GM‐CSF) play an important role in the production of allergic inflammation of the airway through their chemotactic activity for eosinophils. Recent studies have indicated that p38 mitogen‐activated protein (MAP) kinase regulates cytokine expression in various cells; however, the role of p38 MAP kinase in RANTES and GM‐CSF production in human bronchial epithelial cells (BECs) has not yet been determined. Objective In the present study, we examined serine phosphorylation of MKK3 and MKK6 which is the upstream regulator of p38 MAP kinase and p38 MAP kinase activation in tumour necrosis factor (TNF)‐α, interleukin (IL)‐1α and platelet‐activating factor (PAF)‐stimulated BECs and the effect of SB 203580 as the specific inhibitor for p38 MAP kinase activity on RANTES and GM‐CSF expression in order to clarify the intracellular signal regulating RANTES and GM‐CSF production by human BECs. Results The results showed that TNFα, IL‐1α and PAF induced serine phosphorylation of MKK3 and MKK6, and p38 MAP kinase activation in BECs. SB 203580 inhibited p38 MAP kinase activity and RANTES and GM‐CSF production by TNFα‐, IL‐1α‐ or PAF‐stimulated human BECs. Conclusions These results indicate that p38 MAP kinase plays an important role in TNFα‐, IL‐1α‐ or PAF‐activated signalling pathway which regulates RANTES and GM‐CSF production by BECs and that the specific inhibitor for p38 MAP kinase activity might be useful for the treatment of allergic inflammation of the airway. BACKGROUNDRANTES and granulocyte macrophage-colony stimulating factor (GM-CSF) play an important role in the production of allergic inflammation of the airway through their chemotactic activity for eosinophils. Recent studies have indicated that p38 mitogen-activated protein (MAP) kinase regulates cytokine expression in various cells; however, the role of p38 MAP kinase in RANTES and GM-CSF production in human bronchial epithelial cells (BECs) has not yet been determined. OBJECTIVEIn the present study, we examined serine phosphorylation of MKK3 and MKK6 which is the upstream regulator of p38 MAP kinase and p38 MAP kinase activation in tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha and platelet-activating factor (PAF)-stimulated BECs and the effect of SB 203580 as the specific inhibitor for p38 MAP kinase activity on RANTES and GM-CSF expression in order to clarify the intracellular signal regulating RANTES and GM-CSF production by human BECs. RESULTSThe results showed that TNF alpha, IL-1 alpha and PAF induced serine phosphorylation of MKK3 and MKK6, and p38 MAP kinase activation in BECs. SB 203580 inhibited p38 MAP kinase activity and RANTES and GM-CSF production by TNF alpha-, IL-1 alpha- or PAF-stimulated human BECs. CONCLUSIONSThese results indicate that p38 MAP kinase plays an important role in TNF alpha-, IL-1 alpha- or PAF-activated signalling pathway which regulates RANTES and GM-CSF production by BECs and that the specific inhibitor for p38 MAP kinase activity might be useful for the treatment of allergic inflammation of the airway. |
Author | Matsumoto Gon Hashimoto Takeshita Kujime Maruoka Horie Hayashi |
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Keywords | Human Immunopathology Allergy Pathophysiology Respiratory disease Enzyme RANTES Transferases Cytokine Interleukin 1α Inflammation Platelet activating factor Chemokine Respiratory tract Signal transduction Polypeptide Kinase Epithelial cell Tumor necrosis factor α Granulocyte macrophage colony stimulating factor |
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RANTES and granulocyte macrophage‐colony stimulating factor (GM‐CSF) play an important role in the production of allergic inflammation of the airway... RANTES and granulocyte macrophage-colony stimulating factor (GM-CSF) play an important role in the production of allergic inflammation of the airway through... BACKGROUNDRANTES and granulocyte macrophage-colony stimulating factor (GM-CSF) play an important role in the production of allergic inflammation of the airway... |
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SubjectTerms | Allergic diseases Animals Biological and medical sciences Bronchi - cytology Bronchi - drug effects Bronchi - enzymology Bronchi - metabolism bronchial epithelial cells Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors Calcium-Calmodulin-Dependent Protein Kinases - metabolism Calcium-Calmodulin-Dependent Protein Kinases - physiology Cell Line, Transformed Chemokine CCL5 - antagonists & inhibitors Chemokine CCL5 - biosynthesis Enzyme Inhibitors - pharmacology Epithelial Cells - drug effects Epithelial Cells - enzymology Epithelial Cells - metabolism GM-CSF Granulocyte-Macrophage Colony-Stimulating Factor - antagonists & inhibitors Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis Humans Imidazoles - pharmacology Immunopathology interleukin 1^a Interleukin-1 - antagonists & inhibitors Interleukin-1 - physiology MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - immunology Medical sciences Mitogen-Activated Protein Kinases p38 MAP kinase p38 Mitogen-Activated Protein Kinases Platelet Activating Factor - antagonists & inhibitors Platelet Activating Factor - physiology platelet-activating factor Pyridines - pharmacology Rabbits RANTES Respiratory and ent allergic diseases tumor necrosis factor-^a Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor Necrosis Factor-alpha - physiology |
Title | p38 MAP kinase regulates TNFα-, IL-1α- and PAF-induced RANTES and GM-CSF production by human bronchial epithelial cells |
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