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The transcription factor NF-kappaB is a pivotal intracellular regulator of many inflammatory responses and it has been proposed that it represents a potential therapeutic target. As chemokines are important for the progress of an inflammatory response by the recruitment of immuno-competent cells, the role NF-kappaB plays in TNFalpha- or lipopolysaccharides (LPS)-induced chemokine secretion by human monocyte-derived macrophages was examined. Secretion of the CXC chemokines IL-8, GROalpha and ENA-78, induced by TNFalpha, was significantly suppressed by inhibiting NF-kappaB, using overexpression of IkappaBalpha. However, when induced by LPS the expression of these chemokines was unaffected. In contrast, expression of the CC chemokines MIP-1alpha, MCP-1 and RANTES inducedby TNFalpha or LPS was significantly inhibited by the overexpression of IkappaBalpha. Therefore, there appear to be different mechanisms regulating CC and CXC chemokine secretion by macrophages, depending on the stimulus and that TNFalpha and LPS can use different signaling mechanisms in macrophages to regulate chemokine synthesis.

Type

Journal article

Journal

European journal of immunology

Publication Date

07/2002

Volume

32

Pages

2037 - 2045

Addresses

Kennedy Institute of Rheumatology Division, Imperial College Faculty of Medicine, London, GB.

Keywords

Cells, Cultured, Macrophages, Humans, Lipopolysaccharides, Growth Substances, Intercellular Signaling Peptides and Proteins, Tumor Necrosis Factor-alpha, DNA-Binding Proteins, NF-kappa B, Chemokines, CC, Chemokines, CXC, Interleukin-8, Macrophage Inflammatory Proteins, Chemotactic Factors, Gene Expression, I-kappa B Proteins, Chemokine CCL2, Chemokine CCL5, Chemokine CXCL10, Chemokine CXCL1, Chemokine CXCL5, Chemokine CCL3, Chemokine CCL4