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Biomedical subjects

K Chadee

Publications and source records attributed to K Chadee.

At least 19 recordsLinked to original sources

Prostaglandin E2 receptor distribution and function in the gastrointestinal tract.

Prostaglandin E2 (PGE2) is one of the most important biologically active prostanoids found throughout the gastrointestinal tract. Despite the fact that PGE2 regulates many physiological functions of the gut including mucosal protection, gastrointestinal secretion and motility, it is implicated in the pathophysiology of inflammatory bowel diseases (IBD) and colorectal neoplasia. The varied biological functions exerted by PGE2 are through the pharmacologically distinct, G-protein coupled plasma membrane receptors termed EP receptors. Disruptions of various prostanoid receptor genes have helped in unravelling the physiological functions of these receptors. To date, all four subtypes of EP receptors have been individually knocked out in mice and various phenotypes have been reported for each subtype. Similarly, in vitro and in vivo studies using EP receptor agonists and antagonists have helped in uncoupling the diverse functions of PGE2 signalling involving distinct EP receptors in the gut. In this review, we will summarize and conceptualize the salient features of EP receptor subtypes, their regional functions in the gut and how expressions of EP receptors are altered during disease states.

Animals↗

The VSL#3 probiotic formula induces mucin gene expression and secretion in colonic epithelial cells.

Several studies have stressed the importance of the microbiota in the maintenance of the gastrointestinal epithelium. Administration of probiotic bacteria, supplements composed of microbiota constituents, was previously shown to diminish symptoms in patients suffering from inflammatory bowel diseases. This raises the possibility that probiotics may play an active role in enhancing the intestinal barrier at the mucosal surface. In this study, we investigated whether the clinically tested VSL#3 probiotic formula and/or its secreted components can augment the protective mucus layer in vivo and in vitro. For in vivo studies, Wistar rats were orally administered the probiotic mixture VSL#3 on a daily basis for seven days. After treatment, basal luminal mucin content increased by 60%. In addition, we exposed isolated rat colonic loops to the VSL#3 probiotic formula, which significantly stimulated colonic mucin (MUC) secretion and MUC2 gene expression; however, MUC1 and MUC3 gene expression were only slightly elevated. The effect of the VSL#3 mucin secretagogue was also tested in vitro by use of LS 174T colonic epithelial cells. In contrast to the animal studies, cultured cells incubated with VSL#3 bacteria did not exhibit increased mucin secretion. However, the bacterial secreted products contained in the conditioned media stimulated a remarkable mucin secretion effect. Among the three bacterial groups (Lactobacilli, Bifidobacteria, and Streptococci) contained in VSL#3, the Lactobacillus species were the strongest potentiator of mucin secretion in vitro. A preliminary characterization of the putative mucin secretagogue suggested that it was a heat-resistant soluble compound, which is not sensitive to protease and DNase treatment. These findings contribute to a better understanding of the complex and beneficial interaction between colonic epithelial cells and intestinal bacteria.

Animals↗

Molecular cloning of gerbil interleukin 12 and its expression as a bioactive single-chain protein.

Complementary DNAs coding for gerbil interleukin 12 (IL-12) p40/p35 subunits were cloned by a combination of cross species reverse transcriptase-polymerase chain reaction (RT-PCR) and 3' rapid amplification of cDNA ends (RACE) techniques. IL-12 p40/p35 had 79% nucleotide identity and 81% amino acid homology to mouse IL-12 p40/p35. The p40/p35 subunits were expressed as a single polypeptide separated by a short hinge sequence that allowed for proper folding and assembly. COS-7 cells transfected with DNA encoding the single-chain gerbil IL-12 (pSCjIL12) secreted high levels of the protein which stimulated proliferation of ConA-activated gerbil spleen lymphoblasts in a dose-dependent manner.

Amino Acid Sequence↗

Calcium-dependent interleukin-8 gene expression in T84 human colonic epithelial cells.

OBJECTIVE AND DESIGN: IL-8 is a chemokine that activates and recruits neutrophils and plays a major role in intestinal inflammation. Signal transduction pathways mediated by protein kinases are central in regulating IL-8 gene expression, however, little is known about the role of Ca2+ in this event. In this study, we characterize the effect of intracellular Ca2+ on interleukin-8 gene expression in T84 human colonic epithelial cells. MATERIALS AND METHODS: Cells were stimulated with Ca2+ ionophore, A23187 or thapsigargin, a Ca2+-ATPase inhibitor. Semi-quantitative RT-PCR was used to examine IL-8 mRNA and ELISA for protein quantification. Reporter gene techniques were used to determine transcription rate. RESULTS: A23187 and thapsigargin caused a dose- and time-dependent accumulation of IL-8 mRNA and protein production which was dependent on the release of Ca2+ from intracellular stores. FK506, a specific inhibitor of calcineurin, inhibited A23187- and thapsigargin-induced IL-8 mRNA expression in a dose dependent manner. Reporter gene studies and actinomycin D chase experiments showed that A23187 and thapsigargin enhanced IL-8 gene transcription and stabilized IL-8 mRNA transcripts, respectively. CONCLUSION: Intracellular Ca2+ plays an important role in regulating IL-8 transcriptionally and posttranscriptionally through calcium/calmodulin-dependent calcineurin.

Adenocarcinoma↗

The 3'-untranslated region of human interleukin-8 mRNA suppresses IL-8 gene expression.

Although adenosine/uridine (AU)-rich sequences in the 3'-untranslated region (UTR) of the interleukin-8 (IL-8) gene have been suggested to contribute to its post-transcriptional regulation, the molecular basis whereby this occurs still needs to be understood. To investigate the role of the 3'-UTR on human IL-8 gene regulation, chimeric reporter genes were generated by adding full length or differentially deleted 3'-UTR of the IL-8 gene to chloramphenicol acetyltransferase (CAT). Addition of the entire IL-8 3'-UTR markedly reduced CAT mRNA and protein expression in COS 7 cells. In a reporter gene study, IL-8 3'-UTR destabilized CAT mRNA, which was dependent on active transcription in COS 7 cells. A 357-base sequence (nucleotides (nt) 2387-2743 of genomic DNA) within 3'-UTR, designated e, suppressed CAT gene expression by accelerating CAT mRNA turnover. A 26-base AU-rich sequence (nt 2552-2577) within e, containing four AUUUA pentamers that form two UAUUUAUU and one UUAUUUAU octamers, did not suppress CAT gene expression. However, deletion of the AU-rich sequences attenuated the inhibitory effect of e on CAT gene expression. Elimination of the first 100 bases (nt 2386-2486) attenuated the potency of fragment e, but much weaker than elimination of the first 146 bases (nt 2387-2533). This study gives new insights in unravelling the molecular mechanisms involved in the post-transcriptional regulation of the IL-8 gene.

3' Untranslated Regions↗

Persistent epithelial dysfunction and bacterial translocation after resolution of intestinal inflammation.

Epithelial secretion may play an important role in reducing bacterial colonization and translocation in intestine. If so, secretory dysfunction could result in increased susceptibility to infection and inflammation. We investigated whether long-term colonic secretory dysfunction occurs after a bout of colitis and if this is accompanied by an increase in bacterial colonization and translocation. Rats were studied 6 wk after induction of colitis with trinitrobenzene sulfonic acid when inflammation had completely resolved, and epithelial permeability was normal. Intestinal loops were stimulated with either Clostridium difficile toxin A or a phosphodiesterase inhibitor. In vitro, colonic tissue from previously sensitized rats was exposed to antigen (ovalbumin). Secretory responses to all three stimuli were suppressed in rats that had previously had colitis. These rats exhibited increased (16-fold) numbers of colonic aerobic bacteria and increased (>3-fold) bacterial translocation, similar to results in rats studied after resolution of enteritis. Postcolitis bacterial translocation was prevented by daily treatment with an inhibitor of inducible nitric oxide synthase. This study demonstrates that intestinal inflammation results in prolonged impairment of colonic epithelial secretion, which may contribute to increases in bacterial load and bacterial translocation. Epithelial dysfunction of this type could underlie an increased propensity for further bouts of inflammation, a hallmark of diseases such as inflammatory bowel disease.

1-Methyl-3-isobutylxanthine↗

A subunit vaccine candidate region of the Entamoeba histolytica galactose-adherence lectin promotes interleukin-12 gene transcription and protein production in human macrophages.

The cysteine-rich region of the 170-kDa subunit galactose-adherence lectin (Gal-lectin) of Entamoeba histolytica is a subunit vaccine candidate and a protective antigen in the gerbil model of amebiasis. Macrophage-mediated immunity is important for protection against E. histolytica and is activated by Th1 cytokines. As Th1 differentiation is promoted by IL-12, we investigated what portion of the Gal-lectin could stimulate IL-12 in human THP-1 macrophages. Native Gal-lactin stimulated IL-12 p40 / p35 mRNA expression in a dose- and time-dependent manner as measured by reverse transcriptase-PCR. Human immune serum and Gal-lectin mAb inhibition studies identified amino acids (aa) 596 - 998 as immunogenic and containing the IL-12 inducing domain. IFN-gamma priming augmented Gal-lectin-induced IL-12 mRNA expression independent of TNF-alpha and IL-1beta, and was required for IL-12 p70 protein production from macrophages and human peripheral blood mononuclear cells. Gal-lectin plus IFN-gamma stimulated IL-12 p40 and p35 gene transcription with stable mRNA transcripts and a differential requirement for protein synthesis. These results suggest that aa 596 - 998 of the Gal-lectin can confer Th1-mediated protection against amebiasis through IL-12 induction.

Animals↗

The human prostanoid DP receptor stimulates mucin secretion in LS174T cells.

This study demonstrates the localization of the prostaglandin (PG)D(2) receptor (DP) within the mucous-secreting globlet cells of the human colon by in situ hybridization, which suggests a role for DP in mucous secretion. Selective high affinity ligands were used, therefore, to evaluate DP regulation of mucous secretion in LS174T human colonic adenocarcinoma cells. The expression of hDP in LS174T cells was confirmed at the mRNA level by reverse transcriptase-polymerase chain reaction, and at the protein level by radioligand binding assays and signal transduction (cyclic AMP accumulation) assays. PGD(2) and the highly selective DP-specific agonist L-644,698 ((4-(3-(3-(3-hydroxyoctyl)-4-oxo-2-thiazolidinyl) propyl) benzoic acid) (racemate)), but not PGE(2) competed for [(3)H]-PGD(2)-specific binding to LS174T cell membranes (K:(i) values of 0.4 nM and 7 nM, respectively). The DP-specific agonists PGD(2), PGJ(2), BW245C (5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropylhydantoin)), and L-644,698 showed similar potencies in stimulating cyclic AMP accumulation (EC(50) values: 45 - 90 nM) and demonstrated the expected rank order of potency. PGE(2) also elicited cyclic AMP production in this cell line (EC(50) value: 162 nM). The activation of cyclic AMP production by PGD(2) and L-644,698, but not PGE(2), was inhibited by the selective DP antagonist BW A868C. Thus, PGD(2) and L-644,698 act through hDP in LS174T cells. PGD(2), L-644,698 and PGE(2) (an established mucin secretagogue) potently stimulated mucin secretion in LS174T cells in a concentration-dependent manner (EC(50)<50 nM). However, BW A868C effectively antagonized only the mucin secretion mediated by PGD(2) and L-644,698 and not PGE(2). These data support a role for the DP receptor in the regulation of mucous secretion.

Benzoates↗

Lipopolysaccharide modulates cyclooxygenase-2 transcriptionally and posttranscriptionally in human macrophages independently from endogenous IL-1 beta and TNF-alpha.

The pathogenesis of septicemia can be triggered by LPS, a potent stimulus for PG synthesis. The enzyme cyclooxygenase (COX) is a rate-limiting step in PG production. COX exists as two isoforms: COX-1, which is constitutively expressed in most cell types, and COX-2, which is inducible by LPS and cytokines in a variety of cells. In this study we determined the role of the proinflammatory cytokines IL-1 beta and TNF-alpha released by LPS-stimulated U937 human macrophages in the regulation of COX-2. Macrophages exposed to LPS showed a rapid and sustained expression of COX-2 mRNA and protein for up to 48 h, whereas PGE2 production was notably enhanced only after 12 h. LPS increased COX-2 gene transcription and activation of the transcription factor NF-kappa B in a transient manner. LPS-treated macrophages produced high levels of TNF-alpha and moderate amounts of IL-1 beta protein. However, neutralizing Abs against these cytokines had no effect on COX-2 mRNA and protein expression, nor did they affect the stability of COX-2 mRNA. Interestingly, in the presence of LPS or exogenous IL-1 beta, COX-2 transcripts were stabilized, and actinomycin D inhibited their degradation. Only when LPS or IL-1 beta was removed did COX-2 mRNA decay with a t1/2 of >/=5 h. In contrast, dexamethasone promoted a faster decay of the LPS-induced COX-2 transcripts (t1/2 = 2.5 h). These results clearly demonstrate that LPS can regulate COX-2 at both transcriptional and posttranscriptional levels independently from endogenous IL-1 beta and TNF-alpha in human macrophages.

Cyclooxygenase 2↗

Prostaglandin E(2) stimulates rat and human colonic mucin exocytosis via the EP(4) receptor.

BACKGROUND & AIMS: Mucins form an integral part of innate host defenses against intestinal pathogens and irritants. However, the mechanisms whereby mucin secretion is regulated during inflammation are poorly understood. Because prostaglandin E(2) (PGE(2)) is prominent during intestinal inflammation, we investigated its receptor-signaling pathway coupled to mucin exocytosis in the colonic epithelial cell line LS174T and rat colon. METHODS: Reverse-transcription polymerase chain reaction (RT-PCR) and [(3)H]PGE(2) binding assays were used to identify the PGE(2) receptors (EP). Intracellular cyclic adenosine monophosphate ([cAMP](i)) was quantified by enzyme immunoassay. Mucins were metabolically labeled with [(3)H]glucosamine, and mucin secretion was quantified by Sepharose 4B column chromatography, immunoblot analysis, and cesium chloride density gradient centrifugation. RESULTS: RT-PCR and DNA sequence analysis identified EP(2), EP(3), and EP(4) receptors. Mucin secretion and [cAMP](i) production by LS174T cells were stimulated dose-dependently by PGE(2), the EP(4)-receptor agonist 1-OH-PGE(1), and the EP(3)/EP(4) agonist M&B28767 and were inhibited with the adenylate cyclase inhibitor SQ22536. The EP(1), EP(2), and EP(3)/EP(1)-receptor agonists iloprost, butaprost, and sulprostone, respectively, had no effect. Similar results were obtained in rat colonic loop studies confirming that the EP(4) receptor is linked to mucin exocytosis in vivo. [(3)H]PGE(2) binding to cell membranes identified a high-affinity binding site that was competitively inhibited by M&B28767 (EP(3)/EP(4)) > 1-OH-PGE(1) (EP(4)) > sulprostone (EP(3)/EP(1)) > butaprost (EP(2)). CONCLUSIONS: PGE(2) coupling to the EP(4) receptor stimulates [cAMP](i)-dependent mucin exocytosis.

Alprostadil↗

Serum from Entamoeba histolytica-infected gerbils selectively suppresses T cell proliferation by inhibiting interleukin-2 production.

Suppression of T and B cell responses during invasive amebiasis may be serum mediated. The mechanism of serum-mediated suppression of spleen cell lymphoproliferation from gerbils with amebic liver abscess was examined. Compared with uninfected gerbil serum (10%), serum samples collected at days 10, 30, and 60, but not at day 20 after infection, augmented both concanavalin A (Con A; T cell mitogen)- and lipopolysaccharide (LPS; B cell mitogen)-induced proliferation of homologous spleen cells. Only day 20 serum (>5%) inhibited Con A- but not LPS-induced proliferation of spleen cells from uninfected gerbils. The suppressive mechanism was independent of nitric oxide and prostaglandin but involved reduced interleukin (IL)-2 production. Addition of exogenous IL-2 reversed the suppressive effect of day 20 serum on Con A-stimulated proliferation. These results identify a mechanism whereby serum may contribute to transient suppression of T cell responses during Entamoeba histolytica infections.

Animals↗

Intestinal mucins in colonization and host defense against pathogens.

Intestinal mucins are key components of the first line of host defense against intestinal pathogens. These large glycoconjugates secreted by specialized exocrine goblet cells form viscous gels that trap microorganisms and irritants and limit their diffusion to the intestinal epithelium. Moreover, they allow for colonization by indigenous bacterial flora that prevents attachment of pathogenic microbes. The interaction between microbes and mucins involves mucin carbohydrate side chains and microbial adhesin molecules. Certain microorganisms and disease states may alter mucin biochemistry or expression. Although these alterations most likely contribute to disease processes, the full impact of these phenomena are still unclear. The development of mucin-secreting cell lines has facilitated the study of mucin biology and aided our understanding of mucin-microbial interactions.

Animals↗

Prostaglandin E2 stimulates IL-8 gene expression in human colonic epithelial cells by a posttranscriptional mechanism.

Intestinal mucosal epithelial cells produce IL-8, a neutrophil chemoattractant that contributes to mucosal inflammation in various infectious and inflammatory diseases. However, the mediators involved and the molecular regulation of IL-8 production are poorly understood. As PGE2 is central in gut inflammation and modulates a variety of mucosal epithelial cell functions, we determined whether PGE2 can affect the expression of IL-8. Exogenous PGE2 induced the accumulation of IL-8 mRNA and protein production in a dose- and time-dependent manner in T84 human colonic epithelial cells. Forskolin and dibutyryl cAMP, which increase intracellular cAMP, stimulated IL-8 in a fashion similar to that of PGE2. PGE2 and PGE2 receptor agonists coupling through EP4 receptors elevated intracellular cAMP and up-regulated IL-8 mRNA expression by activating protein kinase A. Unlike PMA, PGE2 and forskolin did not increase IL-8 gene transcription. However, PGE2, forskolin, and PMA enhanced the stability of IL-8 mRNA transcripts, suggesting the involvement of posttranscriptional regulation. Chloramphenicol acetyltransferase reporter gene transfection studies confirmed the presence of a PGE2 responsive cis-element(s) in the IL-8 3' untranslated region. Furthermore, dexamethasone inhibited PGE2-, forskolin-, and dibutyryl cAMP-induced, but not PMA-induced, IL-8 protein production. These results highlight a novel role for PGE2 in up-regulating IL-8 gene expression by colonic epithelial cells, which may contribute to exacerbation of inflammation in the gastrointestinal tract.

Adenocarcinoma↗

Novel regulation of cyclooxygenase-2 expression and prostaglandin E2 production by IFN-gamma in human macrophages.

Cyclooxygenase-2 (COX-2) is the inducible enzyme in macrophages responsible for high output PG production during inflammation and immune responses. Although several stimuli are known to regulate COX-2, the molecular mechanisms modulating its expression by the cytokine network are poorly understood. As IFN-gamma priming is essential for macrophage accessory and effector cell functions, we investigated the effect of IFN-gamma on COX-2 expression in U937 human macrophages stimulated with IL-1beta. A dose- and time-dependent increase in COX-2 mRNA and protein expression was evoked by IL-1beta, whereas the levels of COX-1, the constitutively expressed isoform, remained unaltered. Interestingly, IFN-gamma-primed cells showed 40 to 60% lower levels of COX-2 mRNA, protein expression, and PGE2 production as compared with nonprimed cells. IFN-gamma-priming (50-500 U/ml) down-regulated COX-2 expression in a time- and dose-dependent fashion. Furthermore, IFN-gamma inhibited COX-2 gene transcription in response to IL-1beta but not to LPS. In contrast, the rate of decay of COX-2 transcripts in nonprimed and primed macrophages was similar (t1/2 = 3.2 h). The down-regulatory effect of IFN-gamma on IL-1beta-induced COX-2 expression was abrogated with cycloheximide. These results highlight a novel mechanism of COX-2 regulation by IFN-gamma at the transcriptional level, which may affect the outcome of inflammatory and immune conditions.

Cell Line↗

Entamoeba histolytica stimulates interleukin 8 from human colonic epithelial cells without parasite-enterocyte contact.

BACKGROUND & AIMS: The mechanisms involved in the initiation of host mucosal inflammation in amebiasis are not fully understood. This study characterized the effect of Entamoeba histolytica components on interleukin 8 (IL-8) gene expression in human colonic cells. METHODS: Colonic cells were stimulated with amebic proteins, secretory components, or live trophozoites (separated with 0.45-microm pores), and the levels of IL-8 messenger RNA (mRNA) and protein were detected. RESULTS: Live amebae or their components enhanced IL-8 mRNA levels in the colonic cells (T84, LS174T, and Caco-2). In T84 cells, the accumulation of IL-8 mRNA induced by amebic components occurred in a dose- and time-dependent fashion. Increased secretion of IL-8 was noted after 12-hour stimulation; neutralizing antibodies against IL-15 or tumor necrosis factor alpha did not inhibit IL-8 production. Nuclear run-on assays showed that amebae-induced IL-8 gene occurred by a posttranscriptional mechanism. Cycloheximide treatment resulted in superinduction of IL-8 mRNA; however, dexamethasone inhibited E. histolytica-induced IL-8 gene expression. CONCLUSIONS: E. histolytica can directly stimulate the induction of IL-8 by colonic cells in the absence of cell-cell contact or injury.

Animals↗

Survival strategies of Entamoeba histolytica: Modulation of cell-mediated immune responses.

Tissue invasion and disease associated with the protozoan Entamoeba histolytica has long been connected with suppression of host cellular immunity. Dampening of the host's defences may facilitate survival of amoebae in extraintestinal sites and development of the characteristic amoebic abscesses. In recent years, several studies have begun to clarify, at the cellular level, the specific effects E. histolytica has on immune cell accessory and effector cell functions. Here, Darren Campbell and Kris Chadee discuss the parasite's multiple modulatory effects on macrophages and T cells and how this manipulation of immune defences may enable the parasite to remain viable in the host. They suggest the putative amoebic molecules involved and potential modulation by the cytokines: interleukins IL-4 and IL-10 and transforming growth factor-beta.

Journal Article↗

Interleukin (IL)-2, IL-4, and tumor necrosis factor-alpha responses during Entamoeba histolytica liver abscess development in gerbils.

To determine cytokine production patterns during hepatic amebiasis, gerbils were infected with Entamoeba histolytica in the liver. Then spleen and hepatic lymph node cell proliferation and interleukin (IL)-2 (a Th1 marker), IL-4 (a Th2 marker), and tumor necrosis factor-alpha (TNF-alpha) production in response to concanavalin A and amebic antigen in vitro were quantified. Early abscess development (day 5 after inoculation) coincided with IL-2, IL-4, and low TNF-alpha production and strong lymphoproliferative responses, whereas suppression of IL production and lymphoproliferation occurred during acute disease (day 20). Proliferative responses and IL-2 production increased at days 30 and 60 after inoculation, but IL-4 levels remained low. Animals drug-treated at day 20 after inoculation demonstrated high IL-2 and low IL-4 production and resistance to reinfection. While acute hepatic amebiasis in gerbils is accompanied by transient immunosuppression, late infection and resistance to reinfection are associated with IL-2 production but low IL-4 and TNF-alpha production (Th-1-like response).

Animals↗

The tumor necrosis factor alpha-stimulating region of galactose-inhibitable lectin of Entamoeba histolytica activates gamma interferon-primed macrophages for amebicidal activity mediated by nitric oxide.

Entamoeba histolytica adheres via galactose-lectin (Gal-lectin) to human colonic mucins and intestinal epithelial cells as a prerequisite to amebic invasion. Native Gal-lectin is a protective antigen in the gerbil model of amebiasis. Amino acids 596 to 1082 of Gal-lectin mediate E. histolytica adherence to target cells and stimulate tumor necrosis factor alpha (TNF-alpha) production by naive murine bone marrow macrophages (BMM). Resistance to amebiasis requires an effective cell-mediated immune response against E. histolytica trophozoites mediated by nitric oxide (NO) released from activated macrophages. Herein, we determine whether the TNF-alpha-stimulating region of Gal-lectin can activate gamma interferon (IFN-gamma)-primed BMM for NO production and amebicidal activity. Native Gal-lectin (100 to 500 ng/ml) stimulated TNF-alpha and inducible nitric oxide synthase (iNOS) mRNA expression in IFN-gamma-primed BMM as did lipopolysaccharide (100 ng/ml). Primed BMM produced TNF-alpha and NO in response to Gal-lectin in a dose-dependent manner. Antilectin monoclonal antibody IG7, which recognizes a domain (amino acids 596 to 818) of the TNF-alpha mRNA-stimulating region of Gal-lectin, specifically inhibited TNF-alpha and iNOS mRNA induction and TNF-alpha and NO production by primed BMM in response to Gal-lectin (100 ng/ml). Simultaneous treatment of BMM with IFN-gamma and Gal-lectin (100 ng/ml) activated the cells to kill E. histolytica trophozoites, whereas IFN-gamma treatment alone had no effect. In the presence of monoclonal antibody 1G7 or aminoguanidine (an iNOS inhibitor), NO production and amebicidal activity were inhibited >80%. These results suggest that the TNF-alpha-stimulating region of native Gal-lectin is a potent stimulus of IFN-gamma-primed BMM for NO production, which is essential for host defense against amebiasis.

Animals↗