scholarly journals Role of Lipid Rafts and Flagellin in Invasion of Colonic Epithelial Cells by Shiga-Toxigenic Escherichia coli O113:H21

2012 ◽  
Vol 80 (8) ◽  
pp. 2858-2867 ◽  
Author(s):  
Trisha J. Rogers ◽  
Cheleste M. Thorpe ◽  
Adrienne W. Paton ◽  
James C. Paton
Keyword(s):  
Escherichia Coli ◽  
Lipid Rafts ◽  
Kinase Inhibitor ◽  
Interleukin 1 ◽  
Adaptor Protein ◽  
Primary Response ◽  
Serine Kinase ◽  
Neuraminidase Treatment ◽  
Asialo Gm1

ABSTRACTShiga-toxigenicEscherichia coli(STEC) O113:H21 strains that lack the locus of enterocyte effacement (LEE) efficiently invade eukaryotic cellsin vitro, unlike LEE-positive O157:H7 strains. We used afliCdeletion mutant of the O113:H21 STEC strain 98NK2 (98NK2ΔfliC) to show that invasion of colonic epithelial (HCT-8) cells is heavily dependent on production of flagellin, even though adherence to the cells was actually enhanced in the mutant. Flagellin binds and signals through Toll-like receptor 5 (TLR5), but there was no evidence that either TLR5, the adaptor protein myeloid differentiation primary response gene 88 (MyD88), or the serine kinase interleukin-1 receptor-associated kinase (IRAK) were required for invasion of HCT-8 cells by strain 98NK2, as judged by transfection, RNA knockdown, or inhibitor studies. However, pretreatment of cells with anti-asialo-GM1 significantly decreased 98NK2 invasion (by 40.8%), while neuraminidase treatment (which cleaves terminal sialic acid residues, thus converting GM1 into asialo-GM1) significantly increased invasion (by 70.7%). Pretreatment of HCT-8 cells with either the cholesterol-depleting agent methyl-β-cyclodextrin (MβCD) or the tyrosine kinase inhibitor genistein significantly decreased invasion by 98NK2, indicating a potential role for lipid rafts in the invasion mechanism. Confocal microscopy also showed invading 98NK2 colocalized with lipid raft markers caveolin-1 and GM1. Interestingly, anti-asialo-GM1, neuraminidase, MβCD, and genistein have similar effects on the vestigial level of STEC invasion seen for STEC strain 98NK2ΔfliC, indicating that lipid rafts mediate a common step in flagellin-dependent and flagellin-independent cellular invasion.

OCT-1–mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib

Blood ◽  
2006 ◽  
Vol 108 (2) ◽  
pp. 697-704 ◽  
Author(s):  
Deborah L. White ◽  
Verity A. Saunders ◽  
Phuong Dang ◽  
Jane Engler ◽  
Andrew C. W. Zannettino ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Kinase Inhibitor ◽  
Adaptor Protein ◽  
Molecular Response ◽  
Intracellular Uptake ◽  
Interpatient Variability ◽  
Strongly Correlated ◽  
Patient Response ◽  
Ic50 Values

Intrinsic sensitivity of newly diagnosed chronic myeloid leukemia (CML) patients to imatinib (IC50imatinib) correlates with molecular response. IC50imatinib is defined as the in vitro concentration of drug required to reduce phosphorylation of the adaptor protein Crkl by 50%. We now show that interpatient variability in IC50imatinib is mainly due to differences in the efficiency of imatinib intracellular uptake and retention (IUR). In 25 untreated CML patients, the IC50imatinib strongly correlated (R2 = –0.484, P = .014 at 2 μM imatinib) with the IUR of [14C]imatinib. The addition of prazosin, a potent inhibitor of OCT-1 cellular transporter, reduced the IUR and eliminated interpatient variability. IC50 values for the more potent BCR-ABL inhibitor nilotinib (AMN107) did not correlate with IC50imatinib (R2 =–0.0561, P > .05). There was also no correlation between IC50nilotinib and the IUR for [14C]nilotinib (R2 = 0.457, P > .05). Prazosin had no effect on nilotinib IUR, suggesting that influx of nilotinib is not mediated by OCT-1. In conclusion, whereas OCT-1–mediated influx may be a key determinant of molecular response to imatinib, it is unlikely to impact on cellular uptake and patient response to nilotinib. Determining interpatient and interdrug differences in cellular uptake and retention could allow individual optimization of kinase inhibitor therapy.

scholarly journals Hemolytically Active (Acylated) Alpha-Hemolysin Elicits Interleukin-1β (IL-1β) but Augments the Lethality of Escherichia coli by an IL-1- and Tumor Necrosis Factor-Independent Mechanism

1998 ◽  
Vol 66 (9) ◽  
pp. 4215-4221 ◽  
Author(s):  
Thomas G. Gleason ◽  
C. Webster Houlgrave ◽  
Addison K. May ◽  
Traves D. Crabtree ◽  
Robert G. Sawyer ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
E Coli ◽  
Alpha Hemolysin ◽  
Deficient Mice ◽  
Necrosis Factor

ABSTRACT Many pathogenic Escherichia coli produce the toxin alpha-hemolysin (Hly), and lipopolysaccharide (LPS), interleukin-1 (IL-1), and tumor necrosis factor (TNF) have all been recognized as important effector molecules during infections by gram-negative organisms. Despite the characterization of many in vitro effects of hemolysin, no direct relationship has been established between hemolysin, LPS, proinflammatory cytokine production, and E. coli-induced mortality. Previously, we have shown in vivo that hemolysin elicits a distinct IL-1α spike by 4 h into a lethal hemolytic E. coli infection. Using three transformedE. coli strains, WAF108, WAF270, and WAH540 (which produce no Hly [Hlynull], acylated Hly [Hlyactive], or nonacylated Hly [Hlyinactive], respectively), we sought to determine the specific roles of hemolysin acylation, LPS, IL-1, and TNF in mediating the lethality of E. coli infection in mice. WAF270 was 100% lethal in BALB/c, C3H/HeJ, and C57BL/6 mice; in mice pretreated with antibody to the type 1 IL-1 receptor; in type 1 IL-1 receptor-deficient mice; and in dual (type 1 IL-1 receptor-type 1 TNF receptor)-deficient mice at doses which were nonlethal (0%) with both WAF108 and WAH540. At lethal doses, WAF270 killed by 6 ± 2.3 h while WAF108 and WAH540 killed at 36 ± 9.4 and 36 ± 13.8 h, respectively. These differences in mortality were not due to IL-1 or TNF release, and the enhanced expression of LPS, which corresponded to Hly expression, was not likely the primary factor causing mortality. We demonstrate that bacterial fatty acid acylation of hemolysin is required in order for it to elicit IL-1 release by monocytes and to confer its virulence on E. coli.

scholarly journals Interleukin 1 Beta As a Promising Therapeutic Target in ABL Tyrosine Kinase Inhibitor Resistant Chronic Myeloid Leukemia Cells

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4249-4249
Author(s):  
Seiichi Okabe ◽  
Tetsuzo Tauchi ◽  
Yuko Tanaka ◽  
Kazuma Ohyashiki
Keyword(s):  
Gene Expression ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Kinase Inhibitor ◽  
Interleukin 1 ◽  
K562 Cells ◽  
Abl Tyrosine Kinase ◽  
Abl Tyrosine Kinase Inhibitor ◽  
Resistant Cells

Abstract Introduction: Although ABL tyrosine kinase inhibitor (TKI), imatinib, nilotinib and dasatinib have demonstrated the potency against chronic myeloid leukemia (CML) and Philadelphia chromosome (Ph) positive acute lymphoblastic leukemia (Ph+ALL) patients, resistance to ABL TKI can develop in the many patients. It has already reported that ABL kinase domain mutations have been implicated in the pathogenesis of ABL TKI resistance, however, it is fully not known the molecular mechanism of drug resistance ABL TKIs. Therefore, new approach against ABL TKI resistant cells may improve the outcome of Ph-positive leukemia patients. Interleukin-1 (IL-1) is a proinflammatory cytokine and central mediator of innate immunity. IL-1β also controls essential cell responses. Because enhanced IL-1β signaling is reported in patients of hematological malignancies, IL-1β may be the promising therapeutic value in ABL TKI resistant CML patients. Materials and methods: In this study, we established ABL TKI-resistant in vitro cell line models (K562 imatinib-R, K562 nilotinib-R, K562 dasatinib-R, K562 ponatinib-R). We also investigated whether IL-1β was involved in ABL TKI resistant Ph-positive leukemia cells and cytokines were induced by IL-1β in human umbilical vein endothelial cells (HUVEC). Results: We analyzed the relationship of IL-1β signaling pathways and ABL TKI sensitivity by microarray gene expression data from the online Gene Expression Omnibus (GEO). IL-1β is related to imatinib sensitivity and resistant in CML patients from the public microarray datasets of GSE14671. We next examined ABL TKI resistant cell lines (K562 imatinib-R, K562 nilotinib-R, K562 dasatinib-R, K562 ponatinib-R) in this study. BCR-ABL point mutation was not found in ABL TKI resistant cells. BCR-ABL expression levels were not increased in ABL TKI resistant K562 cells. These cells were highly resistant to ABL TKIs compare to K562 cells (K562 imatinib-R: imatinib 2μM, nilotinib-R: nilotinib 2μM, dasatinib-R: dasatinib 100nM, ponatinib-R: ponatinib 50nM). We investigated gene expression profiles in cultured ABL TKI resistant K562 cells by DNA microarray. We found gene expression of IL-1β and IL-1β mediated signaling pathway was increased ABL TKI resistant K562 cells. IL-1β gene amplification was confirmed by RT-PCR analysis. Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB) acts as a central mediator of inflammatory responses. Because bortezomib is a proteasome inhibitor whose anti-cancer action is partly mediated through inhibition of NF-κB, we examined the bortezomib in ABL TKI resistant cells. Combined treatment of ABL TKI resistant cells with ponatinib or imatinib and bortezomib caused more cytotoxicity than each drug alone. Caspase 3/7 activity and cellular cytotoxicity was also increased. ABL TKIs are also associated with vascular adverse events (VAEs) in CML, we next investigated the in vitro effects of ABL TKIs on cultured HUVEC. We found gene expression of IL-1β was increased after ABL TKI especially dasatinib and ponatinib treatment. IL-1β was increased in the cell culture supernatant after ABL TKIs treatment. In the immunoblot analysis, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation was increased by IL-1β in the time dependent manner. We also found that gene expression of IL-6, IL-8, intercellular adhesion molecule 1 (ICAM1) and monocyte chemotactic protein-1 (MCP-1) was enhanced by IL-1β stimulation. Conclusion: The IL-1β signaling pathway is involved in ABL TKI sensitivity and drug resistant in CML cells and plays a key role in cytokine production of the HUVEC. We also provide the promising clinical relevance as a candidate drug for treatment of ABL TKI resistant leukemia patients. Disclosures Ohyashiki: Asahikase: Research Funding; Taiho Pharmaceutical KK: Honoraria, Research Funding; Dainippon Sumitomo KK,: Honoraria, Research Funding; MSD,: Honoraria, Research Funding; Bristol Meyer Squibb KK,: Honoraria, Research Funding; Ono Pharmaceutical KK,: Honoraria, Research Funding; Celegene KK,: Honoraria, Research Funding; Pfizer KK,: Honoraria, Research Funding; Kyowakko Kirin KK,: Research Funding; Nihon-Seiyaku,: Research Funding; Eizai,: Research Funding; Chugai KK,: Honoraria, Research Funding; Takeda Pharmaceutical KK,: Honoraria, Research Funding; Asteras KK,: Research Funding; Jansen Pharma KK,: Research Funding; Nippon-shinyaku,: Honoraria, Research Funding; Novartis KK,: Honoraria, Research Funding.

scholarly journals Role of MyD88 in IL-1β and Ethanol Modulation of GABAergic Transmission in the Central Amygdala

2019 ◽  
Vol 9 (12) ◽  
pp. 361 ◽  
Author(s):  
Michal Bajo ◽  
Reesha R. Patel ◽  
David M. Hedges ◽  
Florence P. Varodayan ◽  
Roman Vlkolinsky ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Motor Coordination ◽  
Interleukin 1 ◽  
Adaptor Protein ◽  
Gaba Release ◽  
Primary Response ◽  
Central Amygdala ◽  
Gabaergic Transmission ◽  
Whole Cell Patch Clamp

Myeloid differentiation primary response protein (MyD88) is a critical neuroimmune adaptor protein in TLR (Toll-like receptor) and IL-1R (Interleukin-1 receptor) signaling complexes. These two pro-inflammatory families play an important role in the neurobiology of alcohol use disorder, specifically MyD88 regulates ethanol drinking, ethanol-induced sedation, and ethanol-induced deficits in motor coordination. In this study, we examined the role of MyD88 in mediating the effects of IL-1β and ethanol on GABAergic transmission in the central amygdala (CeA) of male mice using whole-cell patch-clamp recordings in combination with pharmacological (AS-1, a mimetic that prevents MyD88 recruitment by IL-1R) and genetic (Myd88 knockout mice) approaches. We demonstrate through both approaches that IL-1β and ethanol’s modulatory effects at CeA GABA synapses are not dependent on MyD88. Myd88 knockout potentiated IL-1β’s actions in reducing postsynaptic GABAA receptor function. Pharmacological inhibition of MyD88 modulates IL-1β’s action at CeA GABA synapses similar to Myd88 knockout mice. Additionally, ethanol-induced CeA GABA release was greater in Myd88 knockout mice compared to wildtype controls. Thus, MyD88 is not essential to IL-1β or ethanol regulation of CeA GABA synapses but plays a role in modulating the magnitude of their effects, which may be a potential mechanism by which it regulates ethanol-related behaviors.

scholarly journals The Identification of Raptor as a Substrate for p44/42 MAPK

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1264-1273 ◽  
Author(s):  
Paul Langlais ◽  
Zhengping Yi ◽  
Lawrence J. Mandarino
Keyword(s):  
Kinase Inhibitor ◽  
Mammalian Target Of Rapamycin ◽  
Adaptor Protein ◽  
Phosphorylation Sites ◽  
Phosphatidylinositol 3 Kinase ◽  
Mtor Inhibition ◽  
Mtor Complex 1 ◽  
Mapk Inhibitor ◽  
Phosphatidylinositol 3

Abstract The adaptor protein raptor is the functional identifier for mammalian target of rapamycin (mTOR) complex 1 (mTORC1), acting to target mTOR to specific substrates for phosphorylation and regulation. Using HPLC-electrospray ionization tandem mass spectrometry, we confirmed the phosphorylation of raptor at Ser696, Thr706, Ser721, Ser722, Ser855, Ser859, Ser863, Thr865, Ser877, Ser881, Ser883, and Ser884 and identified Tyr692, Ser699, Thr700, Ser704, Ser854, Ser857, Ser882, Ser886, Ser887, and Thr889 as new, previously unidentified raptor phosphorylation sites. Treatment of cells with insulin increased the phosphorylation of raptor at Ser696, Ser855, Ser863, and Thr865 and suppressed the phosphorylation of Ser722. Ser696 phosphorylation was insensitive to mTOR inhibition with rapamycin, whereas treatment of cells with the MAPK inhibitor PD98059 inhibited the insulin-stimulated phosphorylation of raptor at Ser696. In vitro incubation of raptor with p42 MAPK significantly increased raptor phosphorylation (P < 0.01), whereas phosphorylation of a Ser696Ala mutant was decreased (P < 0.05), suggesting MAPK is capable of directly phosphorylating raptor at Ser696. Mutation of Ser696 to alanine interfered with insulin-stimulated phosphorylation of the mTOR downstream substrate p70S6 kinase. Incubation of cells with the MAPK inhibitor PD98059 and the phosphatidylinositol 3-kinase inhibitor wortmannin decreased the insulin stimulated phosphorylation of raptor, suggesting that the MAPK and phosphatidylinositol 3-kinase pathways may merge at mTORC1.

scholarly journals Interleukin-1 (IL-1) Signaling in Intestinal Stromal Cells Controls KC/CXCL1 Secretion, Which Correlates with Recruitment of IL-22-Secreting Neutrophils at Early Stages of Citrobacter rodentium Infection

2015 ◽  
Vol 83 (8) ◽  
pp. 3257-3267 ◽  
Author(s):  
Yong-Soo Lee ◽  
Hyungjun Yang ◽  
Jin-Young Yang ◽  
Yeji Kim ◽  
Su-Hyun Lee ◽  
...  
Keyword(s):  
Public Health ◽  
Escherichia Coli ◽  
Bacterial Infection ◽  
Stromal Cells ◽  
Interleukin 1 ◽  
Citrobacter Rodentium ◽  
Wild Type ◽  
Content Type ◽  
Health Concerns

Attaching and effacing pathogens, including enterohemorrhagicEscherichia coliin humans andCitrobacter rodentiumin mice, raise serious public health concerns. Here we demonstrate that interleukin-1 receptor (IL-1R) signaling is indispensable for protection againstC. rodentiuminfection in mice. Four days after infection withC. rodentium, there were significantly fewer neutrophils (CD11b+Ly6C+Ly6G+) in the colons of IL-1R−/−mice than in wild-type mice. Levels of mRNA and protein of KC/CXCL1 were also significantly reduced in colon homogenates of infected IL-1R−/−mice relative to wild-type mice. Of note, infiltrated CD11b+Ly6C+Ly6G+neutrophils were the main source of IL-22 secretion afterC. rodentiuminfection. Interestingly, intestinal stromal cells isolated from IL-1R−/−mice secreted lower levels of KC/CXCL1 than stromal cells from wild-type mice duringC. rodentiuminfection. Similar effects were found when mouse intestinal stromal cells and human nasal polyp stromal cells were treated with IL-1R antagonists (i.e., anakinra)in vitro. These results suggest that IL-1 signaling plays a pivotal role in activating mucosal stromal cells to secrete KC/CXCL1, which is essential for infiltration of IL-22-secreting neutrophils upon bacterial infection.

scholarly journals Phycocyanin Exerts Anti-Proliferative Effects through Down-Regulating TIRAP/NF-κB Activity in Human Non-Small Cell Lung Cancer Cells

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 588 ◽  
Author(s):  
Shuai Hao ◽  
Shuang Li ◽  
Jing Wang ◽  
Yan Yan ◽  
Xin Ai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Interleukin 1 ◽  
Adaptor Protein ◽  
Small Cell ◽  
Small Cell Lung ◽  
Sirna Knockdown ◽  
First Time

Phycocyanin is a type of marine functional food additive, exerting a health care efficacy with no side effects. It has been shown that phycocyanin possesses anticancer function in non-small cell lung cancer (NSCLC) cells, but the underlying regulatory mechanism still remains unclear. Further investigation on the antineoplastic mechanism of phycocyanin would provide useful information on NSCLC treatment. In this study, we explored the in vitro function and mechanism of phycocyanin in three typical NSCLC cell lines, H1975, H1650, and LTEP-a2, for the first time. Phenotypic experiments showed that phycocyanin significantly induced the apoptosis as well as suppressed the growth of NSCLC cells. Transcriptome analysis suggested that toll/interleukin 1 receptor domain-containing adaptor protein (TIRAP) was significantly down-regulated by phycocyanin. Strikingly, similar to phycocyanin-treated assays, siRNA knockdown of TIRAP expression also resulted in the anti-proliferative phenomenon in NSCLC cells. In addition, the activity of NF-κB signaling was also suppressed after silencing TIRAP expression, revealing that phycocyanin exerted anti-proliferative function through down-regulating TIRAP/NF-κB activity in NSCLC cells. Collectively, this study has laid a theoretical basis on the treatment of NSCLC and the potential utilization of marine functional products.

scholarly journals Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression

2017 ◽  
Vol 49 (5) ◽  
pp. 1602006 ◽  
Author(s):  
Antonino Di Stefano ◽  
Fabio L.M. Ricciardolo ◽  
Gaetano Caramori ◽  
Ian M. Adcock ◽  
Kian Fan Chung ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Bacterial Load ◽  
Airflow Obstruction ◽  
Adaptor Protein ◽  
Inflammatory Cells ◽  
Primary Response ◽  
Chronic Obstructive ◽  
Bronchial Mucosa ◽  
Bronchial Epithelial ◽  
Bronchial Inflammation

Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial mucosa of subjects with stable COPD of different severity (n=34), control smokers (n=12) and nonsmokers (n=12). The bronchial bacterial load of Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was measured by quantitative real-time PCR.TLR4 and NOD1 expression was increased in the bronchial mucosa of patients with severe/very severe stable COPD compared with control subjects. TLR4 bronchial epithelial expression correlated positively with CD4+ and CD8+ cells and airflow obstruction. NOD1 expression correlated with CD8+ cells. The bronchial load of P. aeruginosa was directly correlated, but H. influenzae inversely correlated, with the degree of airflow obstruction. Bacterial load did not correlate with inflammatory cells.Bronchial epithelial overexpression of TLR4 and NOD1 in severe/very severe stable COPD, associated with increased bronchial inflammation and P. aeruginosa bacterial load, may play a role in the pathogenesis of COPD.

scholarly journals Characterization of Receptor-Mediated Signal Transduction by Escherichia coli Type IIa Heat-Labile Enterotoxin in the Polarized Human Intestinal Cell Line T84

2001 ◽  
Vol 69 (12) ◽  
pp. 7205-7212 ◽  
Author(s):  
Susan Wimer-Mackin ◽  
Randall K. Holmes ◽  
Anne A. Wolf ◽  
Wayne I. Lencer ◽  
Michael G. Jobling
Keyword(s):  
Escherichia Coli ◽  
Signal Transduction ◽  
Lipid Rafts ◽  
Secretory Response ◽  
Ganglioside Gm1 ◽  
T84 Cells ◽  
B Subunit ◽  
Heat Labile ◽  
Functional Receptor

ABSTRACT Escherichia coli type IIa heat-labile enterotoxin (LTIIa) binds in vitro with highest affinity to ganglioside GD1b. It also binds in vitro with lower affinity to several other oligosialogangliosides and to ganglioside GM1, the functional receptor for cholera toxin (CT). In the present study, we characterized receptor-mediated signal transduction by LTIIa in the cultured T84 cell model of human intestinal epithelium. Wild-type LTIIa bound tightly to the apical surface of polarized T84 cell monolayers and elicited a Cl− secretory response. LTIIa activity, unlike CT activity, was not blocked by the B subunit of CT. Furthermore, an LTIIa variant with a T14I substitution in its B subunit, which binds in vitro to ganglioside GM1 but not to ganglioside GD1b, was unable to bind to intact T84 cells and did not elicit a Cl− secretory response. These findings show that ganglioside GM1 on T84 cells is not a functional receptor for LTIIa. The LTIIa receptor on T84 cells was inactivated by treatment with neuraminidase. Furthermore, LTIIa binding was blocked by tetanus toxin C fragment, which binds to gangliosides GD1b and GT1b. These findings support the hypothesis that ganglioside GD1b, or possibly a glycoconjugate with a GD1b-like oligosaccharide, is the functional receptor for LTIIa on T84 cells. The LTIIa-receptor complexes from T84 cells were associated with detergent-insoluble membrane microdomains (lipid rafts), extending the correlation between toxin binding to lipid rafts and toxin function that was previously established for CT. However, the extent of association with lipid rafts and the magnitude of the Cl− secretory response in T84 cells were less for LTIIa than for CT. These properties of LTIIa and the previous finding that enterotoxin LTIIb binds to T84 cells but does not associate with lipid rafts or elicit a Cl− secretory response may explain the low pathogenicity for humans of type II enterotoxin-producing isolates of E. coli.

Sign in / Sign up

Export Citation Format

Share Document