Expression of Organic Anion Transporting Polypeptides in an H-Ras 12V Transgenic Mouse Model of Spontaneous Hepatocellular Carcinoma

Purpose@#Expression of organic anion transporting polypeptides (OATPs) 1B1/1B3 in hepatocellular carcinoma (HCC) induces a paradoxical enhancement of gadoxetic acid on liver magnetic resonance imaging (MRI). We examined the expression profile of OATPs with regard to tumor differentiation in a genetically modified H-Ras 12V mouse model of spontaneous HCC that undergoes multistep hepatocarcinogenesis with minimal inter-individual variation. @*Materials and Methods@#Tumor nodules were harvested from transgenic H-Ras 12V mice. Hematoxylin and eosin-stained slides were examined for tumor differentiation and high-grade pathological components (tumor necrosis, thickened trabeculae, or vascular invasion). Immunohistochemistry of OATP 1B1/1B3 was performed, and OATP expression was assessed. @*Results@#We examined well-differentiated HCCs (n=59) in which high-grade pathological components were absent (n=49) or present (n=10). Among the well-differentiated HCCs without high-grade pathological components (n=49), OATP expression was negative, weak positive, and moderate positive in 23, 17, and nine cases, respectively. Among the well-differentiated HCCs with highgrade pathological components (n=10), OATP expression was negative, weak positive, and moderate positive in one, two, and seven cases, respectively. The ratio of positive OATP 1B1/1B3 expressing tumors was higher in HCCs with high-grade pathological components than in those without high-grade pathological components (p=0.004). @*Conclusion@#Our findings support those of previous clinical studies that have reported the frequent appearance of gadoxetic acidenhanced MRI in moderately differentiated HCC.

Expression of Organic Anion Transporting Polypeptides in an H-Ras 12V Transgenic Mouse Model of Spontaneous Hepatocellular Carcinoma

Purpose@#Expression of organic anion transporting polypeptides (OATPs) 1B1/1B3 in hepatocellular carcinoma (HCC) induces a paradoxical enhancement of gadoxetic acid on liver magnetic resonance imaging (MRI). We examined the expression profile of OATPs with regard to tumor differentiation in a genetically modified H-Ras 12V mouse model of spontaneous HCC that undergoes multistep hepatocarcinogenesis with minimal inter-individual variation. @*Materials and Methods@#Tumor nodules were harvested from transgenic H-Ras 12V mice. Hematoxylin and eosin-stained slides were examined for tumor differentiation and high-grade pathological components (tumor necrosis, thickened trabeculae, or vascular invasion). Immunohistochemistry of OATP 1B1/1B3 was performed, and OATP expression was assessed. @*Results@#We examined well-differentiated HCCs (n=59) in which high-grade pathological components were absent (n=49) or present (n=10). Among the well-differentiated HCCs without high-grade pathological components (n=49), OATP expression was negative, weak positive, and moderate positive in 23, 17, and nine cases, respectively. Among the well-differentiated HCCs with highgrade pathological components (n=10), OATP expression was negative, weak positive, and moderate positive in one, two, and seven cases, respectively. The ratio of positive OATP 1B1/1B3 expressing tumors was higher in HCCs with high-grade pathological components than in those without high-grade pathological components (p=0.004). @*Conclusion@#Our findings support those of previous clinical studies that have reported the frequent appearance of gadoxetic acidenhanced MRI in moderately differentiated HCC.

Two base pair deletion in IL2 receptor γ gene in NOD/SCID mice induces a highly severe immunodeficiency / 한국실험동물학회지

Genome editing has recently emerged as a powerful tool for generating mutant mice. Small deletions of nucleotides in the target genes are frequently found in CRISPR/Cas9 mediated mutant mice. However, there are very few reports analyzing the phenotypes in small deleted mutant mice generated by CRISPR/Cas9. In this study, we generated a mutant by microinjecting sgRNAs targeting the IL2 receptor γ gene and Cas9 protein, into the cytoplasm of IVF-derived NOD.CB17/Prkdcscid/JKrb (NOD/SCID) mice embryos, and further investigated whether a 2 bp deletion of the IL2 receptor γ gene affects severe deficiency of immune cells as seen in NOD/LtSz-scid IL2 receptor γ−/− (NSG) mice. Our results show that the thymus weight of mutant mice is significantly less than that of NOD/SCID mice, whereas the spleen weight was marginally less. T and B cells in the mutant mice were severely deficient, and NK cells were almost absent. In addition, tumor growth was exceedingly increased in the mutant mice transplanted with HepG2, Raji and A549 cells, but not in nude and NOD/SCID mice. These results suggest that the NOD/SCID mice with deletion of 2 bp in the IL2 receptor γ gene shows same phenotype as NSG mice. Taken together, our data indicates that small deletions by genome editing is sufficient to generate null mutant mice.

Relevance of reactive oxygen species in liver disease observed in transgenic mice expressing the hepatitis B virus X protein / 한국실험동물학회지

The hepatitis B virus (HBV) infects approximately 240 million people worldwide, causing chronic liver disease (CLD) and liver cancer. Although numerous studies have been performed to date, unfortunately there is no conclusive drug or treatment for HBV induced liver disease. The hepatitis B virus X (HBx) is considered a key player in inducing CLD and hepatocellular carcinoma (HCC). We generated transgenic (Tg) mice expressing HBx protein, inducing HCC at the age of 11–18 months. The incidence of histological phenotype, including liver tumor, differed depending on the genetic background of HBx Tg mice. Fatty change and tumor generation were observed much earlier in livers of HBx Tg hybrid (C57BL/6 and CBA) (HBx-Tg hybrid) mice than in HBx Tg C57BL/6 (HBx-Tg B6) mice. Inflammation was also enhanced in the HBx-Tg B6 mice as compared to HBx-Tg hybrid mice. HBx may be involved in inducing and promoting hepatic steatosis, glycemia, hepatic fibrosis, and liver cancer. Reactive oxygen species (ROS) generation was remarkably increased in livers of HBx Tg young mice compared to young wild type control mice.Previous studies on HBx Tg mice indicate that the HBx-induced ROS plays a role in inducing and promoting CLD and HCC.

Relevance of reactive oxygen species in liver disease observed in transgenic mice expressing the hepatitis B virus X protein / 한국실험동물학회지

The hepatitis B virus (HBV) infects approximately 240 million people worldwide, causing chronic liver disease (CLD) and liver cancer. Although numerous studies have been performed to date, unfortunately there is no conclusive drug or treatment for HBV induced liver disease. The hepatitis B virus X (HBx) is considered a key player in inducing CLD and hepatocellular carcinoma (HCC). We generated transgenic (Tg) mice expressing HBx protein, inducing HCC at the age of 11–18 months. The incidence of histological phenotype, including liver tumor, differed depending on the genetic background of HBx Tg mice. Fatty change and tumor generation were observed much earlier in livers of HBx Tg hybrid (C57BL/6 and CBA) (HBx-Tg hybrid) mice than in HBx Tg C57BL/6 (HBx-Tg B6) mice. Inflammation was also enhanced in the HBx-Tg B6 mice as compared to HBx-Tg hybrid mice. HBx may be involved in inducing and promoting hepatic steatosis, glycemia, hepatic fibrosis, and liver cancer. Reactive oxygen species (ROS) generation was remarkably increased in livers of HBx Tg young mice compared to young wild type control mice.Previous studies on HBx Tg mice indicate that the HBx-induced ROS plays a role in inducing and promoting CLD and HCC.

STEP signaling pathway mediates psychomotor stimulation and morphine withdrawal symptoms, but not for reward, analgesia and tolerance

Striatal-enriched protein tyrosine phosphatase (STEP) is abundantly expressed in the striatum, which strongly expresses dopamine and opioid receptors and mediates the effects of many drugs of abuse. However, little is known about the role of STEP in opioid receptor function. In the present study, we generated STEP-targeted mice carrying a nonsense mutation (C230X) in the kinase interaction domain of STEP by screening the N-ethyl-N-nitrosourea (ENU)-driven mutant mouse genomic DNA library and subsequent in vitro fertilization. It was confirmed that the C230X nonsense mutation completely abolished functional STEP protein expression in the brain. STEP(C230X−/−) mice showed attenuated acute morphine-induced psychomotor activity and withdrawal symptoms, whereas morphine-induced analgesia, tolerance and reward behaviors were unaffected. STEP(C230X−/−) mice displayed reduced hyperlocomotion in response to intrastriatal injection of the μ-opioid receptor agonist DAMGO, but the behavioral responses to δ- and κ-opioid receptor agonists remained intact. These results suggest that STEP has a key role in the regulation of psychomotor action and physical dependency to morphine. These data suggest that STEP inhibition may be a critical target for the treatment of withdrawal symptoms associated with morphine.

An important role for peroxiredoxin II in survival of A549 lung cancer cells resistant to gefitinib

Redox adaptation is an important concept that explains the mechanisms by which cancer cells survive under persistent endogenous oxidative stress and become resistant to certain anticancer agents. To investigate this concept, we determined the expression levels of peroxiredoxins (Prxs), antioxidant enzymes in drug-resistant non-small cell lung carcinoma cells. Prx II was remarkably increased only in A549/GR (gefitinib-resistant) cells compared with A549 cells, consistent with methylation/demethylation. Prx II was highly methylated in the A549 cells but was demethylated in the A549/GR cells. The elevated expression of Prx II resulted in the downregulation of reactive oxygen species (ROS) and cell death and upregulation of cell cycle progression in the A549/GR cells. When Prx II mRNA in the A549/GR cells was knocked down, the levels of ROS and apoptosis were significantly recovered to the levels of the controls. In addition, signaling molecules involved in apoptosis were increased in the A549/GR-shPrx II cells. There was no difference in the expression of MAPK/ERK between the A549/GR cells and A549/GR-shPrx II cells, but the phosphorylation of JNK was increased in the A549/GR cells and was markedly decreased in the A549/GR-shPrx II cells. Colony number and tumor growth were significantly decreased in the A549/GR-shPrx II cells compared with the A549/GR cells. Our findings suggest that Prx II has an important role in cancer cell survival via the modulation of signaling molecules involved in apoptosis and the phosphorylation of JNK by the downregulation of ROS levels in A549/GR cells.

An important role for peroxiredoxin II in survival of A549 lung cancer cells resistant to gefitinib

Redox adaptation is an important concept that explains the mechanisms by which cancer cells survive under persistent endogenous oxidative stress and become resistant to certain anticancer agents. To investigate this concept, we determined the expression levels of peroxiredoxins (Prxs), antioxidant enzymes in drug-resistant non-small cell lung carcinoma cells. Prx II was remarkably increased only in A549/GR (gefitinib-resistant) cells compared with A549 cells, consistent with methylation/demethylation. Prx II was highly methylated in the A549 cells but was demethylated in the A549/GR cells. The elevated expression of Prx II resulted in the downregulation of reactive oxygen species (ROS) and cell death and upregulation of cell cycle progression in the A549/GR cells. When Prx II mRNA in the A549/GR cells was knocked down, the levels of ROS and apoptosis were significantly recovered to the levels of the controls. In addition, signaling molecules involved in apoptosis were increased in the A549/GR-shPrx II cells. There was no difference in the expression of MAPK/ERK between the A549/GR cells and A549/GR-shPrx II cells, but the phosphorylation of JNK was increased in the A549/GR cells and was markedly decreased in the A549/GR-shPrx II cells. Colony number and tumor growth were significantly decreased in the A549/GR-shPrx II cells compared with the A549/GR cells. Our findings suggest that Prx II has an important role in cancer cell survival via the modulation of signaling molecules involved in apoptosis and the phosphorylation of JNK by the downregulation of ROS levels in A549/GR cells.

The Effect of Metformin Treatment on CRBP-I Level and Cancer Development in the Liver of HBx Transgenic Mice

Retinoids regulate not only various cell functions including proliferation and differentiation but also glucose and lipid metabolism. After we observed a marked up-regulation of cellular retinol-binding protein-I (CRBP-I) in the liver of hepatitis B virus x antigen (HBx)-transgenic (HBx Tg) mice which are prone to hepatocellular carcinoma (HCC) and fatty liver, we aimed to evaluate retinoid pathway, including genes for the retinoid physiology, CRBP-I protein expression, and retinoid levels, in the liver of HBx Tg mice. We also assessed the effect of chronic metformin treatment on HCC development in the mice. Many genes involved in hepatic retinoid physiology, including CRBP-I, were altered and the tissue levels of retinol and all-trans retinoic acid (ATRA) were elevated in the liver of HBx Tg mice compared to those of wild type (WT) control mice. CRBP-I protein expression in liver, but not in white adipose tissue, of HBx Tg mice was significantly elevated compared to WT control mice while CRBP-I protein expressions in the liver and WAT of high-fat fed obese and db/db mice were comparable to WT control mice. Chronic treatment of HBx Tg mice with metformin did not affect the incidence of HCC, but slightly increased hepatic CRBP-I level. In conclusion, hepatic CRBP-I level was markedly up-regulated in HCC-prone HBx Tg mice and neither hepatic CRBP-I nor the development of HCC was suppressed by metformin treatment.

Studies on In Vivo Function of Peroxiredoxins in Knockout Mice / 한양의대학술지

Peroxiredoxins (Prxs) are a family of antioxidant proteins that reduce peroxide levels by using reducing agents such as thioredoxin. These proteins were characterized to have a number of cellular functions, including cell proliferation and differentiation and protection of specific proteins from oxidative damage. Thus, it is important to clarify the physiological role of Prxs by generating mouse models deficient in each Prx to better understand the in vivo function of Prxs. We have generated and characterized mice deficient in Prx I and II that are abundantly expressed in almost all types of cells. The Prx II-/- mice were healthy in appearance and fertile, however showed several pathophysiological disorders. Using the mice, we found that Prx II is an essential antioxidant enzyme that prevents oxidative stress in erythropoiesis, protects against endotoxin-induced lethal shock, regulates platelet-derived growth factor signaling and angiogenesis, inhibits cellular senescence, preserves cognitive function against age-linked hippocampal oxidative damage and exacerbates tumorigenesis in a liver cancer mouse model. The Prx I-/- mice were also healthy in appearance and fertile like Prx II-/- mice. With the mice, we found that Prx I suppresses K-ras-driven lung tumorigenesis by opposing the redox-sensitive extracellular-signal-regulated kinase/cyclin D1 pathway and plays concerted action with sulfiredoxin in preventing against alcohol-induced oxidative injury in the mouse liver. The results obtained suggest that Prx I and II are essential antioxidant enzymes for maintaining redox homeostasis in mice.

The Expression of Estrogen Receptors in Hepatocellular Carcinoma in Korean Patients

Expression of estrogen receptors (ER)-alpha and -beta, as well as androgen receptor (AR), in hepatocellular carcinoma (HCC) is thought to be correlated with prognosis, survival, and male prevalence of HCC. These hypotheses are based on investigations of European patients; however the expression patterns of these receptors in Asian patients are largely unknown. In this study, we collected liver carcinoma and peritumor tissues from 32 patients (9 females and 23 males) in South Korea. The expression of ERs and ARs was studied using RT-PCR. Wild-type ER-alpha and AR were expressed in all of the samples investigated, and their expression was independent of the causal virus or patient sex. Expression of the ER-alpha variant was independent of sex (100% female vs. 91.3% male) and HCV and HBV status (91.3% vs. 100%). Wild-type ER-beta was expressed more often in HCV patients than in HBV patients (95.7% vs. 44.4%; p < 0.05). In conclusion, the stronger ER-alpha variant expression in HCC tissues implies that this variant has an important role in HCC development. However, at least in Korean patients, expression of the ER-alpha variant (vER-alpha) is not related to male HCC prevalence. In addition, the predominant expression of ER-beta in HCV patients suggests that it plays an important role in HCV-induced liver disease.

Expression of the RERG Gene is Gender-Dependent in Hepatocellular Carcinoma and Regulated by Histone Deacetyltransferases

Ras-related, estrogen-regulated, and growth-inhibitory gene (RERG) is a novel gene that was first reported in breast cancer. However, the functions of RERG are largely unknown in other tumor types. In this study, RERG expression was analyzed in hepatocellular carcinomas of human patients using reverse transcriptase PCR analysis. In addition, the possible regulation of RERG expression by histone deacetyltransferases (HDACs) was studied in several cell lines. Interestingly, the expression of RERG gene was increased in hepatocellular carcinoma (HCC) of male patients (57.9%) but decreased in HCC of females (87.5%) comparison with paired peri-tumoral tissues. Moreover, RERG gene expression was increased in murine hepatoma Hepa1-6 cells, human breast tumor MDA-MB-231 cells, and mouse normal fibroblast NIH3T3 cells after treated by HDAC inhibitor, trichostatin A. Our results suggest that RERG may function in a gender-dependent manner in hepatic tumorigenesis and that the expression of this gene may be regulated by an HDAC-related signaling pathway.

Expression of hepatitis C virus nonstructural 4B in transgenic mice

Hepatitis C virus (HCV) is a pathogen that is of great medical significance in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Although the HCV proteins have been intensively investigated over the past decade, the biochemical functions of the NS4B protein are still largely unknown. To investigate NS4B as a potential causative agent of liver disease, transgenic mice expressing the NS4B protein in liver tissue were produced. The transgenic animals were phenotypically similar to their normal littermates for up to 18 months of age. Our results suggest that the HCV NS4B protein is not directly cytopathic or oncogenic in our transgenic mice model.

Transgenic expression of Korean type hepatitis C virus core protein and related mutants in mice

Hepatitis C virus (HCV) is a major causative agent in liver disease. In order to investigate if Korean type HCV core protein and its related mutants, S99Q and S116I, are cytopathic to liver, three types of transgenic mice were established. The expression of transgenes was confirmed by HCV specific RT-PCR and Western immunoblotting. The livers of all wild type core and S116I transgenic lineages remained largely histologically normal. However, the livers of the S99Q transgenic mice showed significant high level of cell dysplasia associated with the transgene expression in hepatocytes largely located around the central veins by in situ hybridization analysis. In conclusion, the mutant HCV core protein at S99Q may contribute to the progress of HCV induced liver disease.

Pathologic Findings in the Liver of Hepatitis B Virus X Transgenic Mice

BACKGROUND: The aim of this study was to investigate the hepatic pathology of HBx transgenic mice. METHODS: The gross and histological examinations were done in 125 HBx transgenic mice and 34 non-transgenic littermates. RESULTS: The incidence of a hepatic tumor was in-creased in the HBx transgenic mice older than 7 months and the overall incidence of a hepatic tumor was 62.2% (51/82) in the 13-18 months group of the HBx transgenic mice. The size of the hepatic tumor was 2.06+/-.92 mm in the 7-12 months group and 4.94+/-.05 mm in the 13-18 months group of HBx transgenic mice. All hepatic tumors were hepatocellular carcinomas and the histological patterns of hepatocellular carcinoma were either solid (84.2%, 48/57) or trabecular (15.8%, 9/57). Dysplastic changes in the hepatocytes were evident in 59.2% (74/125) of the HBx transgenic mice. There was lymphocyte infiltration, necrosis, fatty metamorphosis in both the dysplastic and tumor areas of the HBx transgenic mice. Vascular ectasia was identified in the tumor area of the HBx transgenic mice. CONCLUSIONS: The pathological findings of the HBx transgenic mice were dysplastic changes in the hepatocytes and development of a hepatocellular carcinoma associated with lymphocyte infiltration, necrosis, fatty metamorphosis in the dysplastic area and tumor area of the HBx transgenic mice.

A Study on the Expression of Proliferating Cell Nuclear Antigen and Apoptosis of the Hepatocellular Carcinoma in Human and Hepatitis B Virus X Transgenic Mice

BACKGROUND: This experiment was designed to study the cell kinetics of hepatocellular carcinoma (HCC) in both hepatitis B virus X (HBx) transgenic mice and humans. METHODS: The immunohistochemical stain of proliferating cell nuclear antigen (PCNA) and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay of apoptosis were used on formalin fixed-paraffin embedded tissues. RESULTS: PCNA labeling indices (PCNA-LI) in the liver of HBx transgenic mice were markedly increased in HCC (11.3%) compare to the dysplastic areas (1.3%) and in the liver of non-transgenic littermates (0.1%). There was no significant difference of PCNA-LI in the dysplastic areas between HCC developed mice and non-HCC developed mice. Apoptosis labeling indices (Apoptosis-LI) in both the dysplastic areas and HCC of HBx transgenic mice were similar to those of non-transgenic littermates. PCNA-LI was markedly increased in human HCC (28.9%) compare to the background of HCC (2.9%) and the control liver (2.9%). Apoptosis-LI was decreased in human HCC (0.3%) compare to the background of HCC (0.4%) and the control liver (1.0%). Conclusion : There is a marked increase of cell proliferating activity in human HCC and in HCC of HBx transgenic mice, and there is a decrease of apoptosis in human HCC, but not in HCC of HBx transgenic mice.

Membrane-type Matrix Metalloproteinase-1 Induced Invasive and Angiogenic Activities in Chick Chorioallantoic Membrane (CAM) Model / 대한암학회지

PURPOSE: Matrix metalloproteinases (MMPs) have been reported to play critical roles in the endothelial cell migration and matrix remodeling during angiogenic process. To investigate the roles of the membrane type MMP (MT1-MMP) by the matrix remodeling of endothelial cells, MT1-MMP expression vector was transfected into bovine aortic endothelial cells (BAECs). Increased ex+pression of MT1-MMP in BAECs enhanced the activation of MMP-2, invasion and migration of BAECs. Moreover, the capacity of tube formation was increased by MT1-MMP transfectants. These observations indicate that MT1-MMP is involved in the angiogenic process of endothelial cells in vitro. In this study, we attempted these effects were confirmed in vivo system. MATERIALS AND METHODS: In this study, we used MT1- MMP or Antisense MT1-MMP stable transfectants in HT1080 human fibrosarcoma cells. Chorioallantoic membrane (CAM) assay was used for the detection of angiogenesis in vivo and modified CAM assay for quantification of invasion of MT1-MMP transfected cells. RESULTS: In CAM assay, the formation of microvessels was stimulated by MT1-MMP transfectants. Invasive capacity of HT1080 cells was also increased in a novel in vivo metastasis model, PCR based CAM assay. CONCLUSION: These results identify the function of MT1- MMP during the neovascularization process.

Usefulness of High-Resolution Sonography for Assessement of Hepatocellular Carcinoma in the Transgenic Mice Expressing Hepatitis B Virus X-protein: A Preliminary Study

PURPOSE: To determine the value of high resolution ultrasonography (US) for the detection of hepatocellular carcinoma in the HBx transgenic mice. MATERIALS AND METHODS: Forty-two HBx transgenic mice aged 8-20 (mean, 14) months underwent high-resolution ultrasound using a 10 -12 MHz linear transducer. US findings indicating the presence or absence, number, size and echogenicity of each hepatic tumor were analyzed, and inaddition, color or power Doppler US was used to analyse tumoral vascularity. In each animal, sacrificed less than five hours after US examination, sonographic and pathologic findings were correlated. RESULT: On gross pathologic examination, 20 hepatocellular carcinomas measuring 1.5 -15 (mean, 4.7) mm in diameter were found in 16 mice; US revealed that 17 of the tumors were homogeneous hypoechoic nodules. With regard to tumor detection, sensitivity was 85%, specificity 96%, positive predictive value 0.944, negative predictive value 0.897, and overall accuracy 90%. Doppler US revealed that in three nodules, intratumoral vessels were present. Inthe other 26 mice, gross examination showed that no mass was present; microscopically, however, four nodules measuring 0.3 -1.2 mm were found in four of these animals. Tumoral vascularity detected by color Doppler US corresponded to the intratumoral vessel within the nodules. One peritoneal nodule, confirmed as a metastatic tumor, was found at the greater omentum. CONCLUSION: In HBx transgenic mice, high-resolution US is valuable for the detection of hepatocellular carcinoma.

Serotype and Nucleotide Analysis of Human Rotavirus Isolates in Korea

Rotaviruses belong to Reoviridae causes diarrhea in human beings as well as domestic animals. This study was conducted to see what type of human rotaviruses are distributed in Seoul and Kyung-gi province. Twenty two of 81 patients showed rotavirus positive with diagnostic kit and RNA electropherosis. We isolated all of rotaviruses from the patients. Electropherotypes of 22 isolates showed 4:2:3 :2 patters whereas those migration patterns were long type. All of those isolates belonged to group 4. Twenty out of 22 isolates reacted with monoclonal antibodies specific to G1, P1A and subgroup II, whereas rest of them, 4-29 and K-30 reacted with subgroup I specific monoclonal antibody. The nucleotide sequence of an isolate K-21 showed 98~100% and 90~96% homologies with those of Wa and KU strain, respectively.

Effect of Bovine and Human Lactoferrin on MA 104 Cell Infected with Human Rotavirus

It has long been known that lactoferrin prevents human beings from infection of virus. To prove this activity of lactoferrin, we evaluated the activities of different lactoferrins to an isolate human rotavirus K-21. Bovine lactoferrin inhibited infection of K-21 to MA-104 cell at the concentration of 25.9 microM whereas bovine hydrolysed lactoferrin prevented rotavirus infection at 103.8 microM. However human lactoferrin prevented infection of K-21 at the concentration of 217.5 microM. These data suggested that lactoferrin activity may be unaffected by the intestinal digestive enzymes and bovine lactoferrin is more active than human lactoferrin with respect to prevention of rotavirus infection.