p38 MAP kinase regulates TNFα-, IL-1α- and PAF-induced RANTES and GM-CSF production by human bronchial epithelial cells

• Published in: Clinical and experimental allergy Vol. 30; no. 1; pp. 48 - 55
• Main Authors: HASHIMOTO, S, MATSUMOTO, K, GON, Y, MARUOKA, S, KUJIME, K, HAYASHI, S, TAKESHITA, I, HORIE, T
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.01.2000; Blackwell
• Subjects: 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; 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
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1046/j.1365-2222.2000.00641.x

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.