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Mitogen-activated protein kinase modulation of nuclear factor-kappaB-induced granulocyte macrophage-colony-stimulating factor release from human alveolar macrophages.
Am J Respir Cell Mol Biol. 2004 Mar; 30(3):342-9.AJ

Abstract

Granulocyte macrophage-colony-stimulating factor (GM-CSF), released from alveolar macrophages (AM), is an important regulator of eosinophil, T cell, and macrophage function and survival. We determined the mechanisms of GM-CSF regulation in AM from normal volunteers activated by lipopolysaccharide (LPS) by examining the role of nuclear factor-kappaB (NF-kappaB), and of p38 mitogen-activated protein (MAP) kinase and MAP kinase kinase (MKK-1). PD 098059 (10 microM), an inhibitor of upstream activator of MKK-1, inhibited GM-CSF expression, but the expression of GM-CSF was not inhibited by SB 203580 (10 microM), an inhibitor of p38-MAP kinase. Phosphorylation of extracellular signal-regulated kinase-1 (ERK-1), ERK-2, and p38 MAP kinase by LPS were demonstrated on Western blot analysis. LPS increased NF-kappaB:DNA binding as examined by electrophoretic mobility shift assay, but this was not suppressed by PD 098059 or by SB 203580. LPS induced an increase in NF-kappaB activation as examined by p50 translocation assay without suppression by PD 098059 or by SB 203580. SN50 (100 microM), an inhibitor of NF-kappaB translocation and the specific IKK-2-Inhibitor (AS602868; 10 microM), also prevented GM-CSF expression and release induced by LPS, indicating that GM-CSF release is NF-kappaB-dependent. PD 098059, but not SB 203580, inhibited LPS-induced histone acetyltransferase (HAT) activity, indicating chromatin modification. Furthermore, AS602868 and SN 50 suppressed LPS-induced HAT activity. TSA (10 ng/ml), an inhibitor of histone deacetylase (HDAC), reversed the inhibitory effect of PD 098059, SB 203580, SN 50 and AS602868 on GM-CSF release. GM-CSF expression and release in AM is controlled by NF-kappaB activation, and this is modulated by phosphorylation of MKK-1 and p38 MAP kinase acting on histone acetylation.

Authors+Show Affiliations

University of Cologne, Medizinische Klinik III, Department of Pneumology, Joseph-Stelzmann-Str. 9, 50924 Köln (Cologne), Germany. andrea.koch@uni-koeln.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12871851

Citation

Koch, Andrea, et al. "Mitogen-activated Protein Kinase Modulation of Nuclear factor-kappaB-induced Granulocyte Macrophage-colony-stimulating Factor Release From Human Alveolar Macrophages." American Journal of Respiratory Cell and Molecular Biology, vol. 30, no. 3, 2004, pp. 342-9.
Koch A, Giembycz M, Ito K, et al. Mitogen-activated protein kinase modulation of nuclear factor-kappaB-induced granulocyte macrophage-colony-stimulating factor release from human alveolar macrophages. Am J Respir Cell Mol Biol. 2004;30(3):342-9.
Koch, A., Giembycz, M., Ito, K., Lim, S., Jazrawi, E., Barnes, P. J., Adcock, I., Erdmann, E., & Chung, K. F. (2004). Mitogen-activated protein kinase modulation of nuclear factor-kappaB-induced granulocyte macrophage-colony-stimulating factor release from human alveolar macrophages. American Journal of Respiratory Cell and Molecular Biology, 30(3), 342-9.
Koch A, et al. Mitogen-activated Protein Kinase Modulation of Nuclear factor-kappaB-induced Granulocyte Macrophage-colony-stimulating Factor Release From Human Alveolar Macrophages. Am J Respir Cell Mol Biol. 2004;30(3):342-9. PubMed PMID: 12871851.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitogen-activated protein kinase modulation of nuclear factor-kappaB-induced granulocyte macrophage-colony-stimulating factor release from human alveolar macrophages. AU - Koch,Andrea, AU - Giembycz,Mark, AU - Ito,Kazuhiro, AU - Lim,Sam, AU - Jazrawi,Elen, AU - Barnes,Peter J, AU - Adcock,Ian, AU - Erdmann,Erland, AU - Chung,K Fan, Y1 - 2003/07/18/ PY - 2003/7/23/pubmed PY - 2004/3/31/medline PY - 2003/7/23/entrez SP - 342 EP - 9 JF - American journal of respiratory cell and molecular biology JO - Am J Respir Cell Mol Biol VL - 30 IS - 3 N2 - Granulocyte macrophage-colony-stimulating factor (GM-CSF), released from alveolar macrophages (AM), is an important regulator of eosinophil, T cell, and macrophage function and survival. We determined the mechanisms of GM-CSF regulation in AM from normal volunteers activated by lipopolysaccharide (LPS) by examining the role of nuclear factor-kappaB (NF-kappaB), and of p38 mitogen-activated protein (MAP) kinase and MAP kinase kinase (MKK-1). PD 098059 (10 microM), an inhibitor of upstream activator of MKK-1, inhibited GM-CSF expression, but the expression of GM-CSF was not inhibited by SB 203580 (10 microM), an inhibitor of p38-MAP kinase. Phosphorylation of extracellular signal-regulated kinase-1 (ERK-1), ERK-2, and p38 MAP kinase by LPS were demonstrated on Western blot analysis. LPS increased NF-kappaB:DNA binding as examined by electrophoretic mobility shift assay, but this was not suppressed by PD 098059 or by SB 203580. LPS induced an increase in NF-kappaB activation as examined by p50 translocation assay without suppression by PD 098059 or by SB 203580. SN50 (100 microM), an inhibitor of NF-kappaB translocation and the specific IKK-2-Inhibitor (AS602868; 10 microM), also prevented GM-CSF expression and release induced by LPS, indicating that GM-CSF release is NF-kappaB-dependent. PD 098059, but not SB 203580, inhibited LPS-induced histone acetyltransferase (HAT) activity, indicating chromatin modification. Furthermore, AS602868 and SN 50 suppressed LPS-induced HAT activity. TSA (10 ng/ml), an inhibitor of histone deacetylase (HDAC), reversed the inhibitory effect of PD 098059, SB 203580, SN 50 and AS602868 on GM-CSF release. GM-CSF expression and release in AM is controlled by NF-kappaB activation, and this is modulated by phosphorylation of MKK-1 and p38 MAP kinase acting on histone acetylation. SN - 1044-1549 UR - https://www.unboundmedicine.com/medline/citation/12871851/Mitogen_activated_protein_kinase_modulation_of_nuclear_factor_kappaB_induced_granulocyte_macrophage_colony_stimulating_factor_release_from_human_alveolar_macrophages_ L2 - https://www.atsjournals.org/doi/10.1165/rcmb.2003-0122OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -