Roles of CD14 in LPS-induced liver injury and lethality in mice pretreated with Propionibacterium acnes

Shuto, Yoshihiro; Kataoka, Masashi; Higuchi, Yasunori; Matsuura, Keiko; Hijiya, Naoki; Yamamoto, Shunsuke

doi:10.1016/j.imlet.2004.03.008

Cited by 14 publications

(14 citation statements)

References 33 publications

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“…These results suggested that TLR9 and TLR2 may play a role in sensitization to TLR4 ligand-induced liver injury. While the mechanisms of P. acnes-induced sensitization for LPS-induced liver injury are not fully understood, it has been shown that P. acnes induce granulomas, defined as focal mononuclear cell infiltrates, in the liver and spleen [12][13][14][15][16][17]. We found that similar to P. acnes, TLR9 activation with CpG DNA resulted in granuloma formation in the liver.…”

Section: Tlr9 Ligand Stimulation Results In Sensitization To Lps-indumentioning

confidence: 80%

“…A recent report suggests that TLR9 also plays a role in liver sensitization and inflammatory responses to P. acnes [14]. We and others have previously shown that P. acnes-induced priming to LPS-induced liver injury involves upregulation of the TLR4 co-receptors, CD14 and MD-2 [15][16][17]. IFNc is critical for P. acnes-induced liver injury [12].…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Critical role of Toll-like receptors and the common TLR adaptor, MyD88, in induction of granulomas and liver injury

Velayudham¹,

Hritz²,

Dolganiuc

et al. 2006

Journal of Hepatology

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Section: Tlr9 Ligand Stimulation Results In Sensitization To Lps-indumentioning

confidence: 80%

Section: Introductionmentioning

confidence: 97%

Critical role of Toll-like receptors and the common TLR adaptor, MyD88, in induction of granulomas and liver injury

Velayudham¹,

Hritz²,

Dolganiuc

et al. 2006

Journal of Hepatology

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“…78 Support for an inhibitory role for sCD14 also comes from two in vivo observations: administering recombinant sCD14 can prevent mortality in mice challenged with endotoxin, 79 as can overexpressing sCD14 in transgenic animals. 80 Although the inhibitory mechanism is uncertain, sCD14 promotes LPS efflux from monocytes and diminishes monocyte cytokine production in a dose-dependent fashion. 36 sCD14 thus has the ability to shuttle LPS to cells that express MD-2/TLR4 and from cells that have cellsurface LPS.…”

Section: Modulation Of Target Cell Response Mechanismsmentioning

confidence: 99%

Detoxifying endotoxin: time, place and person

Munford¹

2005

J. Endotoxin Res.

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Animals that cannot sense endotoxin may die if they are infected by Gram-negative bacteria. Animals that sense endotoxin and respond too vigorously may also die, victims of their own inflammatory reactions. The outcome of Gram-negative bacterial infection is thus determined not only by an individual's ability to sense endotoxin and respond to its presence, but also by numerous phenomena that inactivate endotoxin and/or prevent harmful reactions to it. Endotoxin sensing requires the MD-2/TLR4 recognition complex and occurs principally in local tissues and the liver. This review highlights the known detoxification mechanisms, which include: (i) proteins that facilitate LPS sequestration by plasma lipoproteins, prevent interactions between the bioactive lipid A moiety and MD-2/TLR4, or promote cellular uptake via non-signaling pathway(s); (ii) enzymes that deacylate or dephosphorylate lipid A; (iii) mechanisms that remove LPS and Gram-negative bacteria from the bloodstream; and (iv) neuroendocrine adaptations that modulate LPS-induced mediator production or neutralize pro-inflammatory molecules in the circulation. In general, the mechanisms for sensing and detoxifying endotoxin seem to be compartmentalized (local versus systemic), dynamic, and variable between individuals. They may have evolved to confine infection and inflammation to extravascular sites of infection while preventing harmful systemic reactions. Integration of endotoxin sensing and detoxification is essential for successful host defense.

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“…Human hepatocytes were demonstrated to produce CD14 by a mechanism similar to producing acute-phase proteins [10], [11]. In liver tissue, Kupffer cells and sinusoidal endothelial cells express mCD14, while hepatocytes are the main producers of sCD14 in plasma [15]. Billiar et al demonstrated that CD14, TLR4, and MD2 form a multi-receptor complex within the lipid rafts of hepatocytes for LPS uptake and signal activation [16].…”

Section: Introductionmentioning

confidence: 99%

Effects of Hepatocyte CD14 Upregulation during Cholestasis on Endotoxin Sensitivity

et al. 2012

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Cholestasis is frequently related to endotoxemia and inflammatory response. Our previous investigation revealed a significant increase in plasma endotoxin and CD14 levels during biliary atresia. We therefore propose that lipopolysacharides (LPS) may stimulate CD14 production in liver cells and promote the removal of endotoxins. The aims of this study are to test the hypothesis that CD14 is upregulated by LPS and investigate the pathophysiological role of CD14 production during cholestasis. Using Western blotting, qRT-PCR, and promoter activity assay, we demonstrated that LPS was associated with a significant increase in CD14 and MD2 protein and mRNA expression and CD14 promoter activity in C9 rat hepatocytes but not in the HSC-T6 hepatic stellate cell line in vitro . To correlate CD14 expression and endotoxin sensitivity, in vivo biliary LPS administration was performed on rats two weeks after they were subjected to bile duct ligation (BDL) or a sham operation. CD14 expression and endotoxin levels were found to significantly increase after LPS administration in BDL rats. These returned to basal levels after 24 h. In contrast, although endotoxin levels were increased in sham-operated rats given LPS, no increase in CD14 expression was observed. However, mortality within 24 h was more frequent in the BDL animals than in the sham-operated group. In conclusion, cholestasis and LPS stimulation were here found to upregulate hepatic CD14 expression, which may have led to increased endotoxin sensitivity and host proinflammatory reactions, causing organ failure and death in BDL rats.

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Roles of CD14 in LPS-induced liver injury and lethality in mice pretreated with Propionibacterium acnes

Cited by 14 publications

References 33 publications

Critical role of Toll-like receptors and the common TLR adaptor, MyD88, in induction of granulomas and liver injury

Critical role of Toll-like receptors and the common TLR adaptor, MyD88, in induction of granulomas and liver injury

Detoxifying endotoxin: time, place and person

Effects of Hepatocyte CD14 Upregulation during Cholestasis on Endotoxin Sensitivity

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