**1. Introduction**

From the 1960s through to the late 1990s, the F. Hoffman-La Roche laboratories in Basal, Switzerland, were the centre of much of the innovative investigation into the role of vitamins in physiology and pathophysiology. At that time, their laboratories were the leaders in exploring newer concepts of biological actions of vitamins. For vitamin K, an exciting potential development was in the analgesic and anti-inflammatory properties of naphthoquinone compounds; an area that had not previously been considered [1, 2].

The explosion in the understanding of several areas since then, such as cytokine and chemokine biology and physiology, molecular biology of signalling pathways and the genetic translation of these signals, has facilitated the ability to explore molecular events in the cell. With these innovations have come newer understandings of the role of vitamin K in physiology that go

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

beyond the gamma-carboxylation of specific protein glutamyl residues in the vitamin K– dependent proteins [3, 4].

protease that is central to the mechanism of limiting microthrombus formation in organ tissue

Anti-Inflammatory Actions of Vitamin K http://dx.doi.org/10.5772/63891 155

Several important chronic diseases with an inflammatory background have been associated with vitamin K deficiency. These include cystic fibrosis, inflammatory bowel disease, pancreatitis, chronic kidney disease and osteoporosis [15–19]. This review will not address the relationship between vitamin K and these diseases, despite our ongoing interests. We have instead focused our attention on the proposed cellular and molecular aspects of vitamin K in regulating inflammation. With respect to this position, a subject that receives continuing interest is the potential role of vitamin K in the amelioration of signal transduction pathways; specifically, how vitamin K may be able to modulate the stimulus received at the surface of a

cell and the message transmission to the cell nucleus for interpretation and response.

Within cells, there are several primary pathways that are important in communicating the exposure to an insult or injury. Early work on avian retroviruses, and in particular reticuloendotheliosis virus strain T (Rev-T), identified an oncogene (v-rel) capable of transforming avian lymphoid cells [20–22]. Once this oncogene had been characterized in avian systems, work progressed quickly to look at mammalian homologues. This research revealed a mouse homologue, c-rel, which was also found to have homologous character to the fruit fly Drosophila gene '*dorsal*' [23–25]. The Drosophila *dorsal* gene is known to play a fundamental role in dorsal-ventral development of the fly larvae, acting as a translocation factor in the cell nucleus to regulate gene expression. Around the same time, another nuclear translocation factor, with sequencing homology to these signalling factors, was discovered, which became known as

We present a greatly simplified overview of NF-κB signalling, and we recommend that interested readers find some of the excellent review literature that has been published [e.g. 27–

NF-κB is present in nearly all cells and participates in a diverse range of biological functions including inflammation, immunity, differentiation, cell growth, tumourigenesis and apoptosis, that is, from birth to death of a cell. This pathway is a central conductor of the molecular orchestra that is important for normal cell function, but it can become over-activated on a more

We now know that NF-κB is a family of proteins that exist as hetero- or homodimers that have been conserved from primitive organisms through to man [30]. The dimers are normally quiescent in the cytosol of cells through the close association with a regulatory inhibitory protein (IκB), first identified through an inspirational series of denaturation-renaturation experiments [38]. NF-κB becomes activated by the removal of IκB from the complex, which requires IκB phosphorylation by cytosolic kinase enzymes (IKK) [39]. The IκB protein is then tagged, by ubiquitination, for degradation in the proteasome [34, 40]. A family of IκBs have

general level [35] or to a greater degree leading to tumourigenesis [36, 37].

**3.1. Introduction to cell-to-nucleus signalling**

nuclear factor kappa-B (NF-κB) [26].

34] in a complex and engrossing story.

*3.1.1. NF-κB*

beds in sepsis [14].
