Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TLR4”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed2006

Common polymorphisms of toll-like receptors 4 and 9 are associated with the clinical manifestation of malaria during pregnancy.

Toll-like receptors (TLRs) are involved in recognition of and response to Plasmodium falciparum. In 304 primiparous Ghanaian women, we examined whether common TLR4 and TLR9 polymorphisms influence susceptibility to and manifestation of malaria during pregnancy. The TLR variants did not affect P. falciparum prevalence or parasite density. However, in P. falciparum-infected women, both the TLR4 Asp299Gly and the TLR9 T-1486C polymorphisms increased the risk of low birth weight in term infants 6-fold, and, additionally, TLR4 Asp299Gly increased the risk of maternal anemia 5-fold; preterm delivery was not associated with these TLR variants. These findings suggest that TLR4 and TLR9 play a role in the manifestation of malaria during pregnancy.

Adolescent↗
PubMed2005

Generation of a monoclonal antibody agonist to toll-like receptor 4.

Toll-Like Receptor 4 (TLR4) has recently been identified as the lipopolysaccharide (LPS) receptor. Upon stimulation of TLR4 with LPS, a Th1 type cytokine response is observed. This immune modulation is thought to have a potential benefit in anti-tumor therapy. We have generated a TLR4 antibody agonist (5D24.D4) that mimics the action of the natural ligand. 5D24.D4 and LPS stimulation of TLR4 leads to a similar response, including IL-8 secretion, activation of NF-kB-mediated transcription, and the induced expression of an overlapping set of target genes. 5D24.D4 may be beneficial as an adjuvant anti-tumor therapy.

Analysis of Variance↗
PubMed2000

Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades.

MyD88 is an adaptor molecule essential for signaling via the Toll-like receptor (TLR)/IL-1 receptor family. TLR4 is a member of the TLR family and a point mutation in the Tlr4 gene causes hyporesponsiveness to lipopolysaccharide (LPS) in C3H/HeJ mice. We have previously shown that both TLR4- and MyD88-deficient mice are hyporesponsive to LPS. In this study we examined the responsiveness of these two knockout mice to various bacterial cell wall components. Cells from TLR4-deficient mice responded to several kinds of LPS, peptidoglycan and crude cell wall preparation from Gram-positive bacteria and mycobacterial lysates. In contrast, macrophages and splenocytes from MyD88-deficient mice did not respond to any of the bacterial components we tested. These results show that MyD88 is essential for the cellular response to bacterial cell wall components.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Expression and function of Toll-like receptors 2 and 4 in human keratinocytes.

Keratinocytes have the ability to kill pathogenic fungi and bacteria by producing antimicrobial substances. Recent studies suggest that microbial components use signaling molecules of the human Toll-like receptor (TLR) family to transduce signals in various cells. Here we provide evidence that keratinocytes express both TLR2 and TLR4 at the mRNA and protein levels, and show that TLR2 and TLR4 are present in the normal human epidermis in vivo and that their expression is regulated by microbial components. The expression of myeloid differentiation protein gene (MyD88), which is involved in the signaling pathway of many TLR, was also demonstrated in keratinocytes. LPS + IFN-gamma increased the expression of TLR2 and TLR4 50- and 5-fold respectively. Treatment of keratinocytes with Candida albicans, mannan, Mycobacterium tuberculosis or LPS with IFN-gamma resulted in the activation and nuclear translocation of NF-kappaB. Inhibition of NF-kappaB blocked the Candida-killing activity of keratinocytes, suggesting that the antimicrobial effect of keratinocytes requires NF-kappaB activation. LPS + IFN-gamma, C. albicans (4 Candida/KC), peptidoglycan (1 micro g/ml) or M. tuberculosis extract significantly increased IL-8 gene expression after 3 h of treatment (P < 0.05). The increases over the 0-h level were 15-, 8-, 10.8- and 7-fold, respectively. The microbial compound-induced increase in IL-8 gene expression could be inhibited by anti-TLR2 and anti-TLR4 neutralizing antibodies, suggesting that TLRs are involved in the pathogen-induced expression of this pro-inflammatory cytokine. Our findings stress the importance of the role of keratinocytes as a component of innate immunity.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Genetic polymorphisms of CD14, toll-like receptor 4, and caspase-recruitment domain 15 are not associated with necrotizing enterocolitis in very low birth weight infants.

OBJECTIVES: Inadequate response of the innate immune system to bacterial antigens present in the intestinal flora may play a role in the development of necrotizing enterocolitis (NEC). Pattern recognition receptors such as CD14, toll-like receptor (TLR) 4, and caspase-recruitment domain (CARD) 15 bind bacterial lipopolysaccharide and peptidoglycan, and their activation leads to production of inflammatory cytokines. Our aim was to evaluate whether single nucleotide polymorphisms (SNPs) of CD14, TLR4, and CARD15 are associated with the risk of NEC in very low birth weight (VLBW) infants. PATIENTS AND METHODS: We determined the CD14 C-260T, TLR4 A +896G, C +1196T, and CARD15 G +2722C, C +2104T, 3020insC functional SNPs in dried blood samples from 118 VLBW infants (of those, 41 developed NEC) and from 146 healthy term newborns using polymerase chain reaction and restriction fragment length polymorphism methods. We tested the association between genotype and risk of NEC. RESULTS: No significant differences were found in the prevalence of CD14 -260T, TLR4 +896G, +1196T, and CARD15 +2722C, +2104T, 3020insC alleles between VLBW infants and healthy term newborns (P = NS). The frequencies of investigated genotypes were similar in infants with and without NEC (P = NS). Furthermore, we did not find any association between genotype and prematurity or sepsis, which are important risk factors of NEC. CONCLUSIONS: Carrier state of the tested CD14, TLR4, and CARD15 SNPs is not associated with NEC risk in VLBW infants.

Enterocolitis, Necrotizing↗
PubMed2005

Dehydroepiandrosterone modulates toll-like receptor expression on splenic macrophages of mice after severe polymicrobial sepsis.

Toll-like receptors (TLRs) play a pivotal role in the induction of innate immunity after the transactivation of proinflammatory cytokine genes. However, the responses of TLRs during severe polymicrobial sepsis have not been thoroughly examined. Although dehydroepiandrosterone (DHEA), a steroid hormone, is reported to have an immunomodulatory effect after sepsis, the mechanism responsible for its salutary is not known. To investigate this, male ICR/Jcl mice (5-8 weeks old) were subjected to sepsis by cecal ligation and puncture (CLP) or sham operation. The mice received vehicle or DHEA (40 mg/kg body weight) subcutaneously immediately after the surgery. Plasma IL-10 levels and splenic macrophage TNF-alpha production, as well as the expression levels of CD14, TLR2, and TLR4 mRNAs on splenic macrophages, were assessed 6 h after the surgery. The results indicate that mice with sepsis show a marked increase in the plasma IL-10 levels and a decrease in TNF-alpha production by splenic macrophages. TLR2 and TLR4 mRNA expression levels after CLP were significantly lower compared with those after the sham operation. TNF-alpha production and TLR2 and TLR4 mRNA expression on splenic macrophages are restored with DHEA administration. Furthermore, administration of DHEA after CLP delayed the mortality of animals. These results indicate that the anti-inflammatory phase of sepsis induces a marked down-regulation of TLR expression on splenic macrophages; however, administration of DHEA resulted in the restoration of TLR2 and TLR4 mRNA expression.

Adjuvants, Immunologic↗
PubMed2004

Evidence for a role of toll-like receptor 4 in development of chronic allograft rejection after cardiac transplantation.

BACKGROUND: Long-term success of cardiac transplantation is limited by various forms of graft rejection. The specific mechanisms initiating and controlling these highly specialized immune processes remain unclear so far. METHODS: To investigate the role of innate immunity in the development of allograft rejection, we assessed toll-like receptor (TLR)4 expression and typical downstream effects of TLR signaling (B7-1, interleukin [IL]-12, tumor necrosis factor [TNF]-alpha) in circulating CD14+ monocytes in 38 transplant recipients 1 to 3 years and in 10 transplant recipients 6 to 10 years after transplantation and compared them with 20 healthy controls using reverse transcription polymerase chain reaction, flow cytometry, and enzyme-linked immunoadsorbent assay. The results were matched with endothelial function testing as an early clinical indicator of transplant vasculopathy early after transplantation. RESULTS: Allograft endothelial dysfunction (ED) was defined as a compromised coronary flow reserve (CFVR) to acetylcholine (CFVR<2 in 13 of 38 transplant recipients). In these patients, mRNA transcript levels for TLR4 (P<0.05) and surface expression of TLR4 (P<0.005) and B7-1 (P<0.05) on circulating monocytes as well as secretion of IL-12 (P<0.02) and TNF-alpha (P<0.05) were significantly higher than in the remaining 25 patients without ED. Compared with the controls, recipients late after transplantation did not show significantly elevated levels of TLR4 or dependent mediators. These results were compared with mRNA levels in a mice model of acute and chronic rejection. Rejecting mice exhibited elevated mRNA levels for mTLR4 and mB7-1. CONCLUSIONS: Our results suggest activation of innate immunity in heart-transplant recipients through TLR4 contributes to the development of chronic rejection after cardiac transplantation.

Adult↗
PubMed2004

The role of IFN-gamma and Toll-like receptors in nephropathy induced by Toxoplasma gondii infection.

The pathologic links between Toxoplasma gondii infections and renal diseases have not yet been established. Gamma interferon (IFN-gamma) and Toll-like receptors (TLRs) are involved in the host defense mechanism against T. gondii infection. The role of IFN-gamma and TLRs in renal function of T. gondii -infected mice was studied using wild type (WT), TLR2-deficient and TLR4-deficient mice perorally infected with cysts of an avirulent cyst-forming Fukaya strain of T. gondii. T. gondii was abundant in kidneys in IFN-gamma KO (GKO) mice as determined by a quantitative competitive-polymerase chain reaction (QC-PCR). But, T. gondii was not detected in kidneys in WT, TLR2-deficient and TLR4-deficient mice. Interestingly, renal function of TLR2-deficient and TLR4-deficient mice was damaged as evaluated by serum creatinine, serum blood urea nitrogen (BUN), and urine albumin/creatinine ratio (ACR), whereas renal function of GKO and WT mice was not damaged. Histopathology of TLR2-deficient mice exhibited glomerular and extracellular matrix swelling with advancing glomerular tissue proliferation, thickened Bowman's capsules and vacuolization of tubules. Renal immunofluorescence study of T. gondii -infected TLR2-deficient mice displayed positive staining of the glomerular basement membrane, mesangial areas and peritubular capillaries. The damage of kidney from TLR4-deficient mice was less severe compared to TLR2-deficient mice, and histopathological damage of kidney was not observed in WT and GKO mice. These results indicate that TLR2, but not IFN-gamma, plays a role in the protection of the renal function against T. gondii infection.

Animals↗
PubMed2006

Toll-like receptor (TLR) 4 polymorphisms are associated with a chronic course of sarcoidosis.

The aetiology of sarcoidosis, an inflammatory granulomatous multi-system disorder, is unclear. It is thought to be the product of an unknown exogenous antigenic stimulus and an endogenous genetic susceptibility. Toll-like receptors (TLR) are signal molecules essential for the cellular response to bacterial cell wall components. Lipopolysaccharide (LPS), for example, binds to TLR 4. Two different polymorphisms for the TLR4 gene (Asp299Gly and Thr399Ile) have been described recently. This leads to a change in the extracellular matrix function of TLR4 and to impaired LPS signal transduction. We genotyped a total of 141 Caucasian patients with sarcoidosis and 141 healthy unrelated controls for the Asp299Gly and Thr399Ile polymorphisms in the TLR4 gene. The mutations were identified with polymerase chain reaction followed by restriction fragment length polymorphism (RFLP) analysis. Among sarcoidosis patients the prevalence for each Asp299Gly and Thr399Ile mutant allele was 15.6% (22/141). In the control group the prevalence was 5.67% (8/141) (P = 0.07). In the subgroup of patients with acute sarcoidosis there was no difference in the control group (P = 0.93), but there was a highly significant association between patients with a chronic course of sarcoidosis and TLR4 gene polymorphisms (P = 0.01).

Acute Disease↗
PubMed2006

Lipopolysaccharide hyporesponsiveness as a risk factor for intensive care unit hospitalization in infants with respiratory syncitial virus bronchiolitis.

Factors such as genetic heterogeneity in the immune response contribute to respiratory syncytial virus (RSV) bronchiolitis severity. Such heterogeneity may manifest by an aberrant proliferation of phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) in response to lipopolysaccharide (LPS). The proliferation of PBMC was analysed in 52 infants: 21 ambulatory infants with mild RSV bronchiolitis (group I), 26 hospitalized infants with RSV bronchiolitis on ward (group II) and five intensive care unit (ICU) hospitalized infants (group III). Proliferation was analysed in response to negative control, PHA (LPS) and LPS/PHA. The TLR4 mutations were genotyped using reverse-transcriptase-polymerase chain reaction. The optical density (OD) post-LPS/PHA of group II (1.27 +/- 0.63) was significantly higher than group II (0.65 +/- 0.38, P = 0.005) or group I (0.63 +/- 0.33, P = 0.003), suggesting hyporesponsiveness to the LPS attenuation effect. None of the ICU hospitalized infants demonstrated OD readings post-LPS/PHA under the 0.75 threshold as opposed to group I (67% under 0.75) and group II (69%) (P < 0.05). The responses to negative-control, LPS and PHA stimulation alone were similar across groups. The presence of TLR4 mutations (Asp299Gly and Thr399Ile) were associated with severe RSV bronchiolitis and were significantly over-represented in groups II and III. These findings suggest that impairments of PBMC function manifested by hyporesponsiveness to LPS as well as the presence of TLR4 mutations are associated with an increased risk for more severe RSV bronchiolitis in previously healthy infants. A certain threshold of LPS hyporesponsiveness may have a very high negative predictive value for ICU hospitalization, even better than the determination of known TLR4 mutations for this purpose.

Ambulatory Care↗
PubMed2004

Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4.

An understanding of lipopolysaccharide (LPS) signal transduction is a key goal in the effort to provide a molecular basis for the lethal effect of LPS during septic shock and point the way to novel therapies. Rapid progress in this field during the last 6 years has resulted in the discovery of not only the receptor for LPS - Toll-like receptor 4 (TLR4) - but also in a better appreciation of the complexity of the signalling pathways activated by LPS. Soon after the discovery of TLR4, the formation of a receptor complex in response to LPS, consisting of dimerized TLR4 and MD-2, was described. Intracellular events following the formation of this receptor complex depend on different sets of adapters. An early response, which is dependent on MyD88 and MyD88-like adapter (Mal), leads to the activation of nuclear factor-kappaB (NF-kappaB). A later response to LPS makes use of TIR-domain-containing adapter-inducing interferon-beta (TRIF) and TRIF-related adapter molecule (TRAM), and leads to the late activation of NF-kappaB and IRF3, and to the induction of cytokines, chemokines, and other transcription factors. As LPS signal transduction is an area of intense research and rapid progress, this review is intended to sum up our present understanding of the events following LPS binding to TLR4, and we also attempt to create a model of the signalling pathways activated by LPS.

Acute-Phase Proteins↗
PubMed2006

Toll-like receptor interactions: tolerance of MyD88-dependent cytokines but enhancement of MyD88-independent interferon-beta production.

Toll-like receptors (TLRs) signal through two main pathways: a myeloid differentiation factor (MyD)88-dependent pathway that acts via nuclear factor kappaB (NF-kappaB) to induce proinflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha) and a MyD88-independent pathway that acts via type I interferons to increase the expression of interferon-inducible genes. Repeated signalling through TLR4 and a number of other TLRs has been reported to result in a reduction in the subsequent proinflammatory cytokine response, a phenomenon known as TLR tolerance. In this study we have shown that, whilst NF-kappaB activation and production of TNF-alpha and interleukin-12 by murine RAW264.7 and J774.2 cells in response to stimulation by TLR4, -5, -7 or -9, was reduced by prior stimulation with TLR4, -5, -7 or -9 ligands, the primary stimulation of TLR3, which does not use the MyD88 pathway, did not reduce the TNF-alpha or interleukin-12 responses to subsequent TLR stimulation. The response to TLR3 stimulation was not diminished by prior TLR ligand exposure. Furthermore, the production of interferon-beta (IFN-beta) following stimulation of TLR3 or -4, which is MyD88-independent, was increased by prior activation of TLR4, -5, -7 or -9. In contrast, TLR9 ligand-induced IFN-beta production, which is MyD88-dependent, was tolerized by prior TLR stimulation. These results are consistent with differential regulation of MyD88-dependent and MyD88-independent cytokine production following serial activation of TLRs.

Animals↗
PubMed2005

The innate immune response to Entamoeba histolytica lipopeptidophosphoglycan is mediated by toll-like receptors 2 and 4.

Entamoeba histolytica is a human pathogen that may invade the intestinal mucosa, causing amoebic colitis or hepatic abscesses when the trophozoites travel through the portal circulation to the liver. Lipopeptidophosphoglycan (LPPG) is a molecular pattern of E. histolytica recognized by the human immune system. Here we report that LPPG is exposed on the cell surface of E. histolytica trophozoites, and is recognized by the host through toll-like receptor (TLR) 2 and TLR4. Correspondingly, human embryonic kidney (HEK)-293 cells were rendered LPPG responsive through overexpression of TLR2 or TLR4/MD2. Moreover, co-expression of CD14 enhanced LPPG signal transmission through TLR2 and TLR4. The interaction of LPPG with TLR2 and TLR4 resulted in activation of NF-kappaB and release of interleukin (IL)-10, IL-12p40, tumour necrosis factor (TNF)-alpha, and IL-8 from human monocytes. Consistent with these findings, responsiveness of mouse macrophages lacking TLR2 expression (TLR2-/-) or functional TLR4 (TLR4d/d) to E. histolytica LPPG challenge was impaired while double deficient macrophages were unresponsive. In contrast to wild-type control and TLR2-/- animals succumbing to lethal shock syndrome, TLR4d/d mice were resistant to systemic LPPG challenge-induced pathology.

Animals↗
PubMed2005

Cytokine responses to fungal pathogens in Kupffer Cells are Toll-like receptor 4 independent and mediated by tyrosine kinases.

Disseminated fungal infections are increasing. However, the interactions between the body's largest population of tissue macrophages, the Kupffer cells and the fungal pathogens are scarcely understood. The aim of this study was to examine the involvement of Toll-like receptor 4 (TLR4) signalling in cytokine production, using primary cultures of rat and murine Kupffer cells exposed to Aspergillus fumigatus and Candida albicans hyphae and conidia. All fungal components induced the release of tumour necrosis factor-alpha (TNF-alpha), but with delayed kinetics compared with lipopolysaccharide (LPS). Candida albicans was the most potent inducer of TNF-alpha protein and mRNA and the only inducer of interleukin-10 (IL-10) in rat Kupffer cells. All fungal components induced enhanced mRNA levels of macrophage inhibitory protein-2 (MIP-2) in the cells, similar to LPS. Inhibitors of Src tyrosine kinases added to cells prior to stimulation led to attenuation in the release of both TNF-alpha (60%, P < 0.05) and IL-10 (70%, P < 0.05) induced by C. albicans conidia but did not influence the LPS-mediated cytokine release. Murine Kupffer cells (C57BL/10J) also released TNF-alpha as well as the chemokines keratinocyte-derived chemokine (KC) and MIP-2 in response to fungal component. Surprisingly, Kupffer cells from TLR4-deficient C57BL/ScCr mice exhibited significantly enhanced production of KC and MIP-2 upon stimulation by fungal components compared with control littermates (P < 0.05). Our study demonstrates that Aspergillus and Candida components induce cytokine production in rat Kupffer cells and that the response to C. albicans conidia involves Src tyrosine kinases. The experiments with TLR4-deficient Kupffer cells suggest that the cytokine response in these cells to fungal component is not mediated by TLR4.

Animals↗
PubMed2004

Gamma-interferon enhances expression of CD14/MyD88 and subsequent responsiveness to lipopolysaccharide from Actinobacillus actinomycetemcomitans in human gingival fibroblasts.

OBJECTIVES: CD14, toll-like receptor 4 (TLR4) and MyD88 have been shown to mediate responsiveness in host cells to lipopolysaccharide. We investigated here the regulatory effects of inflammatory cytokines on the expression of membrane CD14 (mCD14), TLR4 and MyD88, and on subsequent responsiveness to lipopolysaccharide from Actinobacillus actinomycetemcomitans in human gingival fibroblasts. MATERIALS AND METHODS: Following treatment with either interleukin-1beta, tumor necrosis factor-alpha (TNF-alpha) or gamma-interferon (IFN-gamma), expression of mCD14/TLR4 and MyD88 was determined by flow cytometry and western blotting, respectively. After pretreatment with IFN-gamma, cells were pre-incubated with either anti-CD14 antibody MY4 or anti-TLR4 antibody HTA125 and subsequently treated with A. actinomycetemcomitans lipopolysaccharide. Then, phosphorylation of mitogen-activated protein (MAP) kinases and IkappaBalpha was examined by western blotting, and production of interleukin-6 and interleukin-8 was measured by their respective enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: IFN-gamma stimulated expression of mCD14, whereas -1beta and TNF-alpha did not. Expression of MyD88 but not TLR4 was also enhanced by IFN-gamma. The lipopolysaccharide activated MAP kinases, such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38, and IkappaBalpha and stimulated production of interleukin-6 and interleukin-8. The lipopolysaccharide-stimulated interleukin-6 and interleukin-8 production was markedly inhibited by MY4 or HTA125. Pretreatment with IFN-gamma augmented the following activation of MAP kinases and IkappaBalpha and production of interleukin-6 and interleukin-8 in response to the lipopolysaccharide. CONCLUSIONS: These results suggest that the augmentation by IFN-gamma of the responsiveness to A. actinomycetemcomitans lipopolysaccharide, such as activation of MAP kinases and IkappaBalpha and terminal cytokine production in human gingival fibroblasts, may be partially mediated by up-regulation of CD14 and MyD88 expression.

Adaptor Proteins, Signal Transducing↗
PubMed2007

Potential role for Toll-like receptor 4 in mediating Escherichia coli maltose-binding protein activation of dendritic cells.

The Escherichia coli maltose-binding protein (MBP) is used to increase the stability and solubility of proteins in bacterial protein expression systems and is increasingly being used to facilitate the production and delivery of subunit vaccines against various pathogenic bacteria and viruses. The MBP tag is presumed inert, with minimum effects on the bioactivity of the tagged protein or its biodistribution. However, few studies have characterized the immunological attributes of MBP. Here, we analyze the phenotypic and functional outcomes of MBP-treated dendritic cells (DCs) and show that MBP induces DC activation and production of proinflammatory cytokines (interleukin-1beta [IL-1beta], IL-6, IL-8, tumor necrosis factor alpha, and IL-12p70) within 24 h and strongly increases Ikappabeta phosphorylation in treated cells. Interestingly, phosphorylation of Ikappabeta was largely abrogated by the addition of anti-human Toll-like receptor 4 (TLR4) antibodies, indicating that MBP activates signaling for DC maturation via TLR4. Consistent with this hypothesis, MBP activated the TLR4-expressing cell line 293-hTLR4A but not control cultures to secrete IL-8. The observed data were independent of lipopolysaccharide contamination and support a role for TLR4 in mediating the effects of MBP. These results provide insight into a mechanism by which MBP might enhance immune responses to vaccine fusion proteins.

Adjuvants, Immunologic↗
PubMed2001

Signaling by toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages.

Lipopolysaccharide (LPS) derived from the periodontal pathogen Porphyromonas gingivalis has been reported to differ structurally and functionally from enterobacterial LPS. These studies demonstrate that in contrast to protein-free enterobacterial LPS, a similarly purified preparation of P. gingivalis LPS exhibited potent Toll-like receptor 2 (TLR2), rather than TLR4, agonist activity to elicit gene expression and cytokine secretion in murine macrophages and transfectants. More importantly, TLR2 stimulation by this P. gingivalis LPS preparation resulted in differential expression of a panel of genes that are normally induced in murine macrophages by Escherichia coli LPS. These data suggest that (i) P. gingivalis LPS does not signal through TLR4 and (ii) signaling through TLR2 and through TLR4 differs quantitatively and qualitatively. Our data support the hypothesis that the shared signaling pathways elicited by TLR2 and by TLR4 agonists must diverge in order to account for the distinct patterns of inflammatory gene expression.

Animals↗