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I came across this new study that was so good that I thought I should start a new thread for it. I'll quote a good passage below:
QUOTE: ...Liver sinusoidal endothelial cells constitute the lining or wall of the hepatic sinusoid. They perform important filtration function due to the presence of small fenestrations that allow free diffusion of many substances, but not of particles of the size of chylomicrons, between the blood and the hepatocyte surface. SEC show huge endocytic capacity for many ligands including glycoproteins, components of the extracellular matrix (ECM; such as hyaluronate, collagen fragments, fibronectin, or chondroitin sulphate proteoglycan), immune complexes, transferrin and ceruloplasmin. SEC may function as antigen-presenting cells (APC) in the context of both MHC-I and MHC-II restriction with the resulting development of antigen-specific T-cell tolerance. They are also active in the secretion of cytokines, eicosanoids (i.e., prostanoids and leukotrienes), endothelin-1, nitric oxide, and some ECM components. Kupffer cells are intrasinusoidally located tissue macrophages with a pronounced endocytic and phagocytic capacity. They are in constant contact with gut-derived particulate materials and soluble bacterial products so that a subthreshold level of their activation in the normal liver may be anticipated. Hepatic macrophages secrete potent mediators of the inflammatory response (reactive oxygen species, eicosanoids, nitric oxide, carbon monoxide, TNF-alpha, and other cytokines), and thus control the early phase of liver inflammation, playing an important part in innate immune defense. High exposure of Kupffer cells to bacterial products, especially endotoxin (lipopolysaccharide, LPS), can lead to the intensive production of inflammatory mediators, and ultimately to liver injury. Besides typical macrophage activities, Kupffer cells play an important role in the clearance of senescent and damaged erythrocytes. Liver macrophages modulate immune responses via antigen presentation, suppression of T-cell activation by antigen-presenting sinusoidal endothelial cells via paracrine actions of IL-10, prostanoids, and TNF-alpha, and participation in the development of oral tolerance to bacterial superantigens. Moreover, during liver injury and inflammation, Kupffer cells secrete enzymes and cytokines that may damage hepatocytes, and are active in the remodeling of extracellular matrix... UNQUOTE.
Source: Adv Anat Embryol Cell Biol. 2001;161:III-XIII, 1-151.
Title: Cooperation of liver cells in health and disease. |
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Here's another good passage:
QUOTE: ...In the liver, prostaglandins synthesized from arachidonic acid mainly in Kupffer cells in a response to various inflammatory stimuli, modulate hepatic glucose metabolism by increasing glycogenolysis in adjacent hepatocytes. The release of glucose from glycogen supports the increased demand for energetic fuel by the inflammatory cells such as leukocytes, and additionally enables enhanced glucose turnover in sinusoidal endothelial cells and Kupffer cells which is necessary for effective defense of these cells against invading microorganisms and oxidative stress in the liver. Leukotrienes, another oxidation product of arachidonic acid, have vasoconstrictive, cholestatic, and metabolic effects in the liver. A transcellular synthesis of cysteinyl leukotrienes (LTC4, LTD4, and LTE4) functions in the liver: LTA4, an important intermediate, is synthesized in Kupffer cells, taken up by hepatocytes, converted into the potent LTC4, and then released into extracellular space, acting in a paracrine way on Kupffer and sinusoidal endothelial cells. Thus, hepatocytes are target cells for the action of eicosanoids and the site of their transformation and degradation, but can not directly oxidate arachidonic acid to eicosanoids. UNQUOTE. |
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I think that I have read something interesting in this article : http://www.liversupport.com/wordpress/2008/03/sulfasalazine%e2%80%99s-potential-for-reversing-fibrosi/
QUOTE :
The Signals Responsible
A well-known protein that controls the activity of over 200 genes, nuclear factor-kappa B (NF-κB) emerged as the agent responsible for instructing cells to resist death. Mann explained that the activation of hepatic stellate cells into myofibroblasts was accompanied by an increase in their NF-κB activity. The presence of this protein is believed to be the primary reason why hepatic stellate cells are able to resist death, their demise of which could allow liver tissue to heal. The NF-κB activity is a key player in how much scarring a liver incurs. As hepatic stellate cells resist death, scar formation persists and the liver progresses towards cirrhosis.
UNQUOTE
And they say also that sulfasalazine could be very useful against cirrhosis.
And I have read that sulfasalazine inhibits the arachidonic acid metabolizing enzymes.
See for instance here : http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20(General%20Monographs-%20S)/SALAZOPYRIN.html
QUOTE :
On the lipoxygenase side of the arachidonic acid cascade, sulfasalazine has been shown to exert an inhibitory activity on several enzymes including 5-LO and LTC4 synthetase. In line with this effect sulfasalazine has been shown to inhibit the release of lipoxygenase product from inflammatory cells and tissue.
Taken together, these effects of sulfasalazine on arachidonic acid metabolizing enzymes would lead to a decrease in pro-inflammatory lipoxygenase products with a simultaneous increase in immunosuppressive, anti-inflammatory prostaglandins, which may have a bearing on the clinical activity.
UNQUOTE
Therefore I think more and more that if we haven't arachidonic acid in the cells, it would be possible to cure hepatitis, for instance hepatitis C.
Any thought ? |
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| We are again at the lipoxygenase (5-LOX) here. 5-LOX and its metabolite LTB4 look the worst of all AA stuff - I haven't seen any citation yet showing its benefits. Pretty much responsible for cancer metastasis and allergies (the LTC series). On the other hand there are some "benefits" of the COX-1,2 (cyclooxygenase) class AA metabolites such as for reproduction, stem cell, immune tolerance and muscle growth. That's why the selective 5-LOX inhibitors such as AKBA have so positive effects and COX inhibitors such as aspirin/NSAIDS always come with side negative effects. The most interesting thing is that the best natural 5-LOX inhibitor is Mead acid ... |
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