Activation of PKC-beta isoforms mediates HNE-induced MCP-1 release by macrophages.
4-Hydroxynonenal (HNE) in the concentration range detectable in many pathophysiologic conditions is able to modulate signal transduction cascades and gene expression. Here, we report the stimulating effect of 1 microM HNE on the release of the monocyte chemotactic protein-1 (MCP-1) by murine macrophages. MCP-1-increased export following 1-h cell treatment with HNE proved to be comparable to that exerted by standard amounts of bacterial lipopolysaccharide (LPS). However, the key molecular event in HNE-induced secretion of MCP-1 appeared to be the increased activity of beta-PKC isoforms, which are recognized as playing a role in the regulation of cell protein transport and secretion. On the other hand, in LPS-stimulated cells, the delta isoform was seen to be involved and was probably related to LPS-mediated effects on MCP-1 expression and synthesis. In conclusion, HNE might interact with other pro-inflammatory stimuli, like LPS, in a concerted amplification of MCP-1 production and secretion.
Nitti
M
M
Department of Experimental Medicine, General Pathology Section, University of Genoa, Via L.B. Alberti, 2, 16132 Genoa, Italy.
Domenicotti
C
C
d'Abramo
C
C
Assereto
S
S
Cottalasso
D
D
Melloni
E
E
Poli
G
G
Biasi
F
F
Marinari
U M
UM
Pronzato
M A
MA
D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D015398:Signal Transduction / Q000187:drug effects
D000447:Aldehydes; D018932:Chemokine CCL2; D015853:Cysteine Proteinase Inhibitors; D007527:Isoenzymes; D011493:Protein Kinase C; D064546:Protein Kinase C beta; C027576:4-hydroxy-2-nonenal