TNFalpha-induced macrophage chemokine secretion is more dependent on NF-kappaB expression than lipopolysaccharides-induced macrophage chemokine secretion.

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, th...

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Main Authors: Ciesielski, C, Andreakos, E, Foxwell, B, Feldmann, M
Format: Journal article
Language:English
Published: 2002
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author Ciesielski, C
Andreakos, E
Foxwell, B
Feldmann, M
author_facet Ciesielski, C
Andreakos, E
Foxwell, B
Feldmann, M
author_sort Ciesielski, C
collection OXFORD
description 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.
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spelling oxford-uuid:5940c69e-30da-4921-a0c1-b03c1f9d987c2022-03-26T17:08:46ZTNFalpha-induced macrophage chemokine secretion is more dependent on NF-kappaB expression than lipopolysaccharides-induced macrophage chemokine secretion.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5940c69e-30da-4921-a0c1-b03c1f9d987cEnglishSymplectic Elements at Oxford2002Ciesielski, CAndreakos, EFoxwell, BFeldmann, MThe 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.
spellingShingle Ciesielski, C
Andreakos, E
Foxwell, B
Feldmann, M
TNFalpha-induced macrophage chemokine secretion is more dependent on NF-kappaB expression than lipopolysaccharides-induced macrophage chemokine secretion.
title TNFalpha-induced macrophage chemokine secretion is more dependent on NF-kappaB expression than lipopolysaccharides-induced macrophage chemokine secretion.
title_full TNFalpha-induced macrophage chemokine secretion is more dependent on NF-kappaB expression than lipopolysaccharides-induced macrophage chemokine secretion.
title_fullStr TNFalpha-induced macrophage chemokine secretion is more dependent on NF-kappaB expression than lipopolysaccharides-induced macrophage chemokine secretion.
title_full_unstemmed TNFalpha-induced macrophage chemokine secretion is more dependent on NF-kappaB expression than lipopolysaccharides-induced macrophage chemokine secretion.
title_short TNFalpha-induced macrophage chemokine secretion is more dependent on NF-kappaB expression than lipopolysaccharides-induced macrophage chemokine secretion.
title_sort tnfalpha induced macrophage chemokine secretion is more dependent on nf kappab expression than lipopolysaccharides induced macrophage chemokine secretion
work_keys_str_mv AT ciesielskic tnfalphainducedmacrophagechemokinesecretionismoredependentonnfkappabexpressionthanlipopolysaccharidesinducedmacrophagechemokinesecretion
AT andreakose tnfalphainducedmacrophagechemokinesecretionismoredependentonnfkappabexpressionthanlipopolysaccharidesinducedmacrophagechemokinesecretion
AT foxwellb tnfalphainducedmacrophagechemokinesecretionismoredependentonnfkappabexpressionthanlipopolysaccharidesinducedmacrophagechemokinesecretion
AT feldmannm tnfalphainducedmacrophagechemokinesecretionismoredependentonnfkappabexpressionthanlipopolysaccharidesinducedmacrophagechemokinesecretion