Bacterial Lipopolysaccharide Activates NF-κB through Toll-like Receptor 4 (TLR-4) in Cultured Human Dermal Endothelial Cells

Faure, Emmanuelle; Equils, Ozlem; Sieling, Peter A.; Thomas, Lisa S.; Zhang, Xiao Hui; Kirschning, Carsten J.; Polentarutti, Nadia; Muzio, Marta; Arditi, Moshe

doi:10.1074/jbc.275.15.11058

Cited by 512 publications

(471 citation statements)

References 34 publications

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“…2C. Of interest, we found that the HMEC endothelial cells expressed surface TLR4 but failed to express TLR2 (data not shown), as has been reported by others (51).…”

Section: Human Cervical and Vaginal Epithelial Cells Express A Distinsupporting

confidence: 82%

Response toNeisseria gonorrhoeaeby Cervicovaginal Epithelial Cells Occurs in the Absence of Toll-Like Receptor 4-Mediated Signaling

Fichorova

Cronin

Lien

et al. 2002

The Journal of Immunology

211

174

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Toll-like receptors (TLRs) have recently been identified as fundamental components of the innate immune response to bacterial pathogens. We investigated the role of TLR signaling in immune defense of the mucosal epithelial cells of the lower female genital tract. This site provides first line defense against microbial pathogens while remaining tolerant to a complex biosystem of resident microbiota. Epithelial cells derived from normal human vagina, ectocervix, and endocervix expressed mRNA for TLR1, -2, -3, -5, and -6. However, they failed to express TLR4 as well as MD2, two essential components of the receptor complex for LPS in phagocytes and endothelial cells. Consistent with this, endocervical epithelial cells were unresponsive to protein-free preparations of lipooligosaccharide from Neisseria gonorrhoeae and LPS from Escherichia coli. However, they were capable of responding to whole Gram-negative bacteria and bacterial lysates, as demonstrated by NF-κB activation and proinflammatory cytokine production. The presence of soluble CD14, a high-affinity receptor for LPS and other bacterial ligands, enhanced the sensitivity of genital tract epithelial cells to both low and high concentrations of bacteria, suggesting that soluble CD14 can act as a coreceptor for non-TLR4 ligands. These data demonstrate that the response to N. gonorrhoeae and other Gram-negative bacteria at the mucosal surface of the female genital tract occurs in the absence of endotoxin recognition and TLR4-mediated signaling.

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“…2C. Of interest, we found that the HMEC endothelial cells expressed surface TLR4 but failed to express TLR2 (data not shown), as has been reported by others (51).…”

Section: Human Cervical and Vaginal Epithelial Cells Express A Distinsupporting

confidence: 82%

Response toNeisseria gonorrhoeaeby Cervicovaginal Epithelial Cells Occurs in the Absence of Toll-Like Receptor 4-Mediated Signaling

Fichorova

Cronin

Lien

et al. 2002

The Journal of Immunology

211

174

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“…Therefore, it can be postulated that the increase of TLR2 depended on the increases of NF-κB. However, several studies have shown a lack of human or murine TLR2 involvement in LPS signaling [15,20,41]. Also, it is possible that the mammary epithelia cells or gland may have its own specific manner of responding to the presence of pathogenic products which may be different from other cell types and organs.…”

Section: Discussionmentioning

confidence: 99%

Bacterial lipopolysaccharide induces increased expression of toll-like receptor (TLR) 4 and downstream TLR signaling molecules in bovine mammary epithelial cells

et al. 2007

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-Bovine mammary epithelial cells contribute to the innate immune response to intramammary infections by recognizing pathogens through specialized pattern recognition receptors. Toll-like receptor 4 (TLR4) is one such receptor that binds and is activated by lipopolysaccharide (LPS), a component of the outer envelope of Gram-negative bacteria. In this study, MAC-T cells (a bovine mammary epithelial cell line) were incubated in the presence or absence of increasing concentrations of LPS for 24 h. Expression of TLR2 and TLR4 were analyzed at both mRNA and protein levels by quantitative real-time PCR (qPCR) and flow cytometry, respectively. The mRNA of both receptors were up-regulated by all concentrations of LPS used (P < 0.01). Similarly, flow cytometry with specific antibodies against TLR2 and TLR4 detected increased surface expression of these proteins. Furthermore, expression of downstream TLR4 signaling molecules was examined by qPCR following varying exposure times to 1 μg/mL of LPS. Results demonstrate that the required adaptor molecules and transcription factors were up-regulated in a time-dependent manner. Both the MyD88 dependent and independent pathways in TLR4 signaling were activated in MAC-T cells. Expression of TOLLIP increased in response to LPS as did the pro-apoptotic protease, CASP8. These results suggest that the bovine mammary epithelium possesses the necessary immune repertoires required to achieve a robust defense against E. coli. The current findings, coupled with previous findings that S. aureus ligands induce up-regulation of TLR4, may indicate a positive adaptation by mammary epithelial cells to effectively respond to different types of mastitis pathogens.lipopolysaccharide / TLR4 and TLR2 / signal transduction / bovine mammary epithelial cells / mastitis

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“…Human umbilical vein EC (HUVEC) express high levels of TLR4 and low amounts of TLR1, TLR2, and TLR6 [47,48]. Increased expression of TLR2 by EC in response to inflammatory mediators such as TNF, LPS, IL-1β, IFNγ and histamine in vivo and in vitro [49][50][51][52], however, provides a mechanism allowing EC to respond to TLR2 ligands under inflammatory conditions.…”

Section: The Role Of Members Of the Tlr Familymentioning

confidence: 99%

Receptors involved in cell activation by antiphospholipid antibodies

Brandt

Kruithof

Moerloose

2013

Thrombosis Research

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The antiphospholipid syndrome (APS) is an autoimmune disease associated with arterial or venous thrombosis and/or recurrent fetal loss and is caused by pathogenic antiphospholipid antibodies (aPLA). The plasma protein β2-glycoprotein 1 (β2GP1) has been identified as a major target of aPLA associated with APS. Cell activation by aPLA appears to be a major pathogenic cause in the pathogenesis of APS. Receptors, co-receptors and accessory molecules are known to assist the pathogenic effects of aPLA. Members of the TLR family and the platelet receptor apolipoprotein E receptor 2' (apoER2'), a receptor belonging to the low-density lipoprotein receptor (LDL-R) family, as well as GPIbα, were identified as putative candidates for aPLA recognition. CD14, a co-receptor for TLR2 and TLR4, and annexin A2, a ubiquitous Ca2+ -binding protein that is essential for actin-dependent vesicle transport, could serve as important accessory molecules in mediating the pathogenic effects of aPLA. Finally, complement activation has been reported in association with the pathogenicity of APS. The relative contribution of these different mechanisms in the pathogenesis of APS is controversial. Here, we review the various in vivo and in vitro models that have been used to investigate the pathogenic mechanisms of aPLA in APS

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Bacterial Lipopolysaccharide Activates NF-κB through Toll-like Receptor 4 (TLR-4) in Cultured Human Dermal Endothelial Cells

Cited by 512 publications

References 34 publications

Response toNeisseria gonorrhoeaeby Cervicovaginal Epithelial Cells Occurs in the Absence of Toll-Like Receptor 4-Mediated Signaling

Response toNeisseria gonorrhoeaeby Cervicovaginal Epithelial Cells Occurs in the Absence of Toll-Like Receptor 4-Mediated Signaling

Bacterial lipopolysaccharide induces increased expression of toll-like receptor (TLR) 4 and downstream TLR signaling molecules in bovine mammary epithelial cells

Receptors involved in cell activation by antiphospholipid antibodies

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