Induction of TNF-α and MnSOD by endotoxin: role of membrane CD14 and Toll-like receptor-4

Tsan, Min‐Fu; Clark, Robert N.; Goyert, Sanna M.; White, J. E.

doi:10.1152/ajpcell.2001.280.6.c1422

Cited by 57 publications

(42 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, it was suggested that Mn-SOD was associated with mucosal defense against H. pylori infection [37]. TLR-mediated expression of Mn-SOD has been reported in macrophages challenged with different TLR ligands [38,39] and our study is the first to indicate that it is up-regulated in epithelial cells upon TLR2 activation. Our observation that saLP induces the expression of Mn-SOD suggests that TLR activation leads to a protective mechanism to reduce cell damage that might be caused by host inflammatory response.…”

Section: Discussionsupporting

confidence: 61%

Staphylococcus aureus lipoproteins trigger human corneal epithelial innate response through toll-like receptor-2

Kumar

Gui

et al. 2008

Microbial Pathogenesis

View full text Add to dashboard Cite

Bacterial lipoproteins (LP) are a family of cell wall components found in a wide variety of bacteria. In this study, we characterized the response of HUCL, a telomerase-immortalized human corneal epithelial cell (HCEC) line, to LP isolated from Staphylococcus (S) aureus. S. aureus LP (saLP) prepared by Triton X-114 extraction stimulated the activation of NF-kB, JNK, and P38 signaling pathways in HUCL cells. The extracts failed to stimulate NF-kB activation in HUCL cells after lipoprotein lipase treatment and in cell lines expressing TLR4 or TLR9, but not TLR2, indicating lipoprotein nature of the extracts. saLP induced the up-regulation of a variety of inflammatory cytokines and chemokines (IL-6, IL-8, ICAM-1), antimicrobial molecules (hBD-2, LL-37, and iNOS), and homeostasis genes (Mn-SOD) at both the mRNA level and protein level. Similar inflammatory response to saLP was also observed in primarily cultured HCECs using the production of IL-6 as readout. Moreover, TLR2 neutralizing antibody blocked the saLP-induced secretion of IL-6, IL-8 and hBD2 in HUCL cells. Our findings suggest that saLP activates TLR2 and triggers innate immune response in the cornea to S. aureus infection via production of proinflammatory cytokines and defense molecules. r

show abstract

Section: Discussionsupporting

confidence: 61%

Staphylococcus aureus lipoproteins trigger human corneal epithelial innate response through toll-like receptor-2

Kumar

Gui

et al. 2008

Microbial Pathogenesis

View full text Add to dashboard Cite

show abstract

“…These findings suggest that the mutation that shapes LPS susceptibility probably exerts its effect in a cell-specific way (Gibbs et al 1992). Tsan et al (2001) additionally demonstrated that induction of MnSOD by LPS is mediated by mCD14 and TLR4 in murine macrophages.…”

Section: Me Low-grade Inflammation and Oxidative Stressmentioning

confidence: 71%

Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk

Neves¹,

Coelho²,

Couto³

et al. 2013

Journal of Molecular Endocrinology

180

140

View full text Add to dashboard Cite

Obesity is associated with significantly increased cardiovascular (CV) risk and mortality. Several molecular mechanisms underlying this association have been implied, among which the intestinal barrier has gained a growing interest. In experimental models of obesity, significant alterations in the intestinal barrier lead to increased intestinal permeability, favoring translocation of microbiome-derived lipopolysaccharide to the bloodstream. This has been shown to result in a two-to threefold increase in its serum concentrations, a threshold named 'metabolic endotoxemia' (ME). ME may trigger toll-like receptor 4-mediated inflammatory activation, eliciting a chronic low-grade proinflammatory and pro-oxidative stress status, which may result in high CV risk and target-organ damage. In this review, we discuss the potential molecular implications of ME on several CV risk factors, such as obesity, insulin resistance, dyslipidemia, and oxidative stress, as well as its potential impact on the development of CV target-organ disease.

show abstract

“…For example, Tsan et al (49) reported that LPS was unable to induce TNF and manganese superoxide dismutase in isolated, CD14 Ϫ/Ϫ peritoneal macrophages at low concentrations but could induce TNF and manganese superoxide dismutase at higher concentrations of LPS. Similar concentration-dependent findings have been reported in peritoneal macrophages for TNF message and for certain LPS-inducible genes including IL12 (p35 and p40) and COX-2 (50).…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-Induced Leukocyte-Endothelial Cell Interactions: A Role for CD14 Versus Toll-Like Receptor 4 Within Microvessels

Andonegui

Goyert

Kubes

2002

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

The objective of this study was to systematically assess leukocyte-endothelial cell interactions in vivo in response to LPS in CD14-deficient (CD14−/−) and Toll-like receptor 4-deficient (TLR4d; C3H/HeJ) mice. Local injection of LPS (0.05 μg/kg) into muscle at a concentration that did not cause systemic effects produced a significant reduction in the speed with which leukocytes roll and a substantial increase in leukocyte adhesion and emigration 4 h postinjection. There was no response to LPS in the muscle microvasculature of CD14−/− mice or TLR4d animals. Systemic LPS induced leukopenia and significant sequestration of neutrophils in lungs in wild-type mice but not in CD14−/− or TLR4d mice. P-selectin expression was examined in numerous mouse organs using a dual radiolabeling mAb technique. The results revealed a 20- to 50-fold increase in P-selectin expression in response to LPS in all wild-type tissues examined but no response in any TLR4d tissues. Surprisingly, there was consistently a partial, significant increase in P-selectin expression in numerous microvasculatures including skin and pancreas, but no increase in P-selectin was detected in lung, muscle, and other organs in CD14−/− mice in response to LPS. Next, the skin and muscle microcirculation were visualized using intravital microscopy after systemic LPS treatment, and the results confirmed a CD14-independent mechanism of leukocyte sequestration in skin but not muscle. In summary, our results suggest that the LPS-induced leukocyte sequestration to some tissues is entirely dependent on both CD14 and TLR4 but there are CD14-independent, TLR4-dependent endothelial cell responses in some microvascular beds.

show abstract

Induction of TNF-α and MnSOD by endotoxin: role of membrane CD14 and Toll-like receptor-4

Cited by 57 publications

References 36 publications

Staphylococcus aureus lipoproteins trigger human corneal epithelial innate response through toll-like receptor-2

Staphylococcus aureus lipoproteins trigger human corneal epithelial innate response through toll-like receptor-2

Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk

Lipopolysaccharide-Induced Leukocyte-Endothelial Cell Interactions: A Role for CD14 Versus Toll-Like Receptor 4 Within Microvessels

Contact Info

Product

Resources

About