Signal transduction in monocytes: the role of zinc ions.
The availability of zinc has a regulatory role in the immune system. It can have either pro- or anti-inflammatory effects, which both seem to be a consequence of a direct interaction of zinc with the cytokine secretion by monocytes. In this review, the molecular basis for this effect, the interaction of zinc with the signal transduction of monocytes, is discussed. In particular, zinc seems to activate or inhibit several signaling pathways that interact with the signal transduction of pathogen sensing receptors, the so-called Toll-like receptors (TLR), which sense pathogen-derived molecular structures and, upon activation, lead to secretion of pro-inflammatory cytokines. The interaction of zinc with protein tyrosine phosphatases and protein kinase C, and a direct modulation of lipopolysaccharide binding to its receptor (TLR-4) all result in enhanced cytokine production. On the other hand, a complex interaction between zinc, NO and cyclic nucleotide signaling, and inhibition of interleukin-1 receptor associated kinase-1, and inhibitor of kappa B kinase all counteract the production of pro-inflammatory cytokines. A role for the zinc binding protein metallothionein as a regulator for intracellular zinc signaling is discussed. By acting on all these signaling molecules, the zinc status of monocytes can have a direct effect on inflammation.
Haase
Hajo
H
Institute of Immunology, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany. hhaase@ukaachen.de
Rink
Lothar
L
D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D007477:Ions / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008668:Metallothionein / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009712:Nucleotides, Cyclic / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D015032:Zinc / Q000737:chemistry / Q000276:immunology*
D007477:Ions; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009712:Nucleotides, Cyclic; D014443:Tyrosine; D008668:Metallothionein; D053592:Interleukin-1 Receptor-Associated Kinases; D011493:Protein Kinase C; D015032:Zinc