LPS-mediated NF-kappa beta activation in rat Kupffer cells can be induced independently of CD14

Bellezzo, Joseph M.; Britton, Robert S.; Bacon, Bruce R.; Fox, Eben S.

doi:10.1152/ajpgi.1996.270.6.g956

Cited by 50 publications

(63 citation statements)

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“…3). These findings corroborate the hypothesis that KC are activated by LPS independently of CD14 via an alternative and more sensitive pathway (51).…”

Section: Mechanism Of the Synergistic Action Of C5a And Lps On Il-6 Rsupporting

confidence: 89%

Anaphylatoxin C5a Actions in Rat Liver: Synergistic Enhancement by C5a of Lipopolysaccharide-Dependent α2-Macroglobulin Gene Expression in Hepatocytes Via IL-6 Release from Kupffer Cells

Mack¹,

Jungermann²,

Götze

et al. 2001

The Journal of Immunology

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The effects of the anaphylatoxins C5a and C3a on the liver are only poorly characterized in contrast to their well known systemic actions. Recently, it has been demonstrated that the anaphylatoxin C5a enhanced glucose output from hepatocytes (HC) indirectly via prostanoid release from Kupffer cells (KC). In the present study, it is shown that recombinant rat C5a (rrC5a), together with LPS, activated the gene of the acute phase protein α2-macroglobulin (α2MG) in HC also indirectly via IL-6 release from KC. RrC5a alone increased neither IL-6 mRNA in nor IL-6 release from KC, whereas LPS alone did so. However, rrC5a synergistically enhanced the LPS-dependent increase in IL-6 mRNA and IL-6 release. Only rIL-6, but not TNF-α or IL-1β, enhanced α2MG mRNA in HC. In line with the actions of rrC5a and LPS on KC, conditioned medium of KC stimulated only with rrC5a did not increase α2MG mRNA in HC. However, medium of KC stimulated with rrC5a plus LPS induced α2MG mRNA expression in HC more strongly than medium from cells stimulated only with LPS; thus, C5a acted synergistically with LPS. The stimulatory effects of KC-conditioned medium could partially be inhibited by a neutralizing anti-IL-6 Ab, indicating that KC-derived IL-6 was a major mediator in C5a- plus LPS-elicited α2MG gene expression. These results suggest that C5a, besides enhancing glucose output via prostanoids, is involved in the initiation of the acute phase response in HC via proinflammatory cytokines from KC. This provides evidence for another important function of C5a in the regulation of hepatocellular defense reactions.

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“…3). These findings corroborate the hypothesis that KC are activated by LPS independently of CD14 via an alternative and more sensitive pathway (51).…”

Section: Mechanism Of the Synergistic Action Of C5a And Lps On Il-6 Rsupporting

confidence: 89%

Anaphylatoxin C5a Actions in Rat Liver: Synergistic Enhancement by C5a of Lipopolysaccharide-Dependent α2-Macroglobulin Gene Expression in Hepatocytes Via IL-6 Release from Kupffer Cells

Mack¹,

Jungermann²,

Götze

et al. 2001

The Journal of Immunology

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“…In the presence of LPS as a source of oxidative stress, the activation of NF-jB was markedly enhanced, consistent with previous reports. 28 On the other hand, RAW 264.7 cells treated with LPS and UG extract (100 lg/mL) caused an inhibition of NF-jB. Figure 6 shows the levels of iNOS mRNA expression from HT29 cells treated with LPS (1 lg/mL) and/or UG extract (50±200 lg/mL).…”

Section: Levels Of Nitrite/nitratementioning

confidence: 97%

Antiinflammatory actions of cat’s claw: the role of NF‐κB

Sandoval-Chacon¹,

Thompson²,

Zhang³

et al. 1998

Aliment Pharmacol Ther

112

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Background: Uncaria tomentosa is a vine commonly known as cat’s claw or ‘uña de gato’ (UG) and is used in traditional Peruvian medicine for the treatment of a wide range of health problems, particularly digestive complaints and arthritis. Purpose: The aim of this study was to determine the proposed anti‐inflammatory properties of cat’s claw. Specifically: (i) does a bark extract of cat’s claw protect against oxidant‐induced stress in vitro, and (ii) to determine if UG modifies transcriptionally regulated events. Methods: Cell death was determined in two cell lines, RAW 264.7 and HT29 in response to peroxynitrite (PN, 300 μM). Gene expression of inducible nitric oxide synthase (iNOS) in HT29 cells, direct effects on nitric oxide and peroxynitrite levels, and activation of NF‐κB in RAW 264.7 cells as influenced by UG were assessed. Chronic intestinal inflammation was induced in rats with indomethacin (7.5 mg/kg), with UG administered orally in the drinking water (5 mg/mL). Results: The administration of UG (100 μg/mL) attenuated (P < 0.05) peroxynitrite‐induced apoptosis in HT29 (epithelial) and RAW 264.7 cells (macrophage). Cat’s claw inhibited lipopolysaccharide‐induced iNOS gene expression, nitrite formation, cell death and inhibited the activation of NF‐κB. Cat’s claw markedly attenuated indomethacin‐enteritis as evident by reduced myeloperoxidase activity, morphometric damage and liver metallothionein expression. Conclusions: Cat’s claw protects cells against oxidative stress and negated the activation of NF‐κB. These studies provide a mechanistic evidence for the widely held belief that cat’s claw is an effective anti‐inflammatory agent.

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“…In the intact animal, much of the LPS in the blood is associated with a specific serum protein, LPS binding protein (LBP). 34 In macrophages, the CD14 antigen has been identified as an LPS receptor and binds to the LPS-LBP complex with a high affinity. 35 However, other investigators have reported that LPS can activate KCs in the absence of LBP.…”

Section: Lps-mediated Inos Mrna Formation In Kcs Is Independent Ofmentioning

confidence: 99%

Suppression of lipopolysaccharide-induced nitric oxide synthase expression by platelet-activating factor receptor antagonists in the rat liver and cultured rat kupffer cells

1999

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Excessive nitric oxide (NO) generated by hepatic cells in response to lipopolysaccharide (LPS) and inflammatory substances (e.g., platelet-activating factor [PAF]) is a key contributor to the pathophysiological outcomes observed in the liver during sepsis. In rats subjected to liver-focused endotoxemia, inducible nitric oxide synthase (iNOS) levels in the intact liver were elevated by 6 hours; cell-specific expression of iNOS messenger RNA (

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LPS-mediated NF-kappa beta activation in rat Kupffer cells can be induced independently of CD14

Cited by 50 publications

References 0 publications

Anaphylatoxin C5a Actions in Rat Liver: Synergistic Enhancement by C5a of Lipopolysaccharide-Dependent α2-Macroglobulin Gene Expression in Hepatocytes Via IL-6 Release from Kupffer Cells

Anaphylatoxin C5a Actions in Rat Liver: Synergistic Enhancement by C5a of Lipopolysaccharide-Dependent α2-Macroglobulin Gene Expression in Hepatocytes Via IL-6 Release from Kupffer Cells

Antiinflammatory actions of cat’s claw: the role of NF‐κB

Suppression of lipopolysaccharide-induced nitric oxide synthase expression by platelet-activating factor receptor antagonists in the rat liver and cultured rat kupffer cells

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