Biomedical subjects

Eun Mi Lee

Publications and source records attributed to Eun Mi Lee.

14 recordsLinked to original sources

PubMed2007

A replication-competent adenovirus-human immunodeficiency virus (Ad-HIV) tat and Ad-HIV env priming/Tat and envelope protein boosting regimen elicits enhanced protective efficacy against simian/human immunodeficiency virus SHIV89.6P challenge in rhesus macaques.

We previously demonstrated that replication-competent adenovirus (Ad)-simian immunodeficiency virus (SIV) recombinant prime/protein boost regimens elicit potent immunogenicity and strong, durable protection of rhesus macaques against SIV(mac251). Additionally, native Tat vaccines have conferred strong protection against simian/human immunodeficiency virus SHIV(89.6P) challenge of cynomolgus monkeys, while native, inactivated, or vectored Tat vaccines have failed to elicit similar protective efficacy in rhesus macaques. Here we asked if priming rhesus macaques with replicating Ad-human immunodeficiency virus (HIV) tat and boosting with the Tat protein would elicit protection against SHIV(89.6P). We also evaluated a Tat/Env regimen, adding an Ad-HIV env recombinant and envelope protein boost to test whether envelope antibodies would augment acute-phase protection. Further, expecting cellular immunity to enhance chronic viremia control, we tested a multigenic group: Ad-HIV tat, -HIV env, -SIV gag, and -SIV nef recombinants and Tat, Env, and Nef proteins. All regimens were immunogenic. A hierarchy was observed in enzyme-linked immunospot responses (with the strongest response for Env, followed by Gag, followed by Nef, followed by Tat) and antibody titers (with the highest titer for Env, followed by Tat, followed by Nef, followed by Gag). Following intravenous SHIV(89.6P) challenge, all macaques became infected. Compared to controls, no protection was seen in the Tat-only group, confirming previous reports for rhesus macaques. However, the multigenic group blunted acute viremia by approximately 1 log (P = 0.017), and both the multigenic and Tat/Env groups reduced chronic viremia by 3 and 4 logs, respectively, compared to controls (multigenic, P = 0.0003; Tat/Env, P < 0.0001). The strikingly greater reduction in the Tat/Env group than in the multigenic group (P = 0.014) was correlated with Tat and Env binding antibodies. Since prechallenge anti-Env antibodies lacked SHIV(89.6P)-neutralizing activity, other functional anti-Env and anti-Tat activities are under investigation, as is a possible synergy between the Tat and Env immunogens.

Adenoviridae↗

PubMed2007

Relationship of thyroid stimulating hormone with coronary atherosclerosis in angina patients.

BACKGROUND: In the previous recent reports, subclinical hypothyroidism is an independent risk factor for acute myocardial infarction in elderly women. It was not established whether a normal range of thyroid stimulating hormone (TSH) influences the presence of coronary atherosclerosis. We postulated that the level of TSH is risk factor of coronary atherosclerosis in angina patients who have normal thyroid function. METHODS: We studied 344 angina patients (62.5+/-9.72 years, male 50%) who underwent elective coronary angiography. TSH, free thyroxine, serum lipid levels and high-sensitivity C-reactive protein levels were measured and compared to the severity of coronary artery disease. RESULTS: In patients with high level of TSH (> or =2.1 microIU/mL), age (p=0.016), the levels of serum creatinine (p=0.004) and Gensini's score (p=0.016) were significantly higher than those in patients with low TSH levels. The incidence of multi-vessel disease was higher in patients with high TSH level (p=0.026). TSH level showed a significant correlation with age (r=0.109, p=0.044) and Gensini's score (r=0.117, p=0.045). The multivariate analysis revealed that age (OR 2.39, p=0.001), diabetes (OR 3.74, p=0.001), creatinine (OR 2.06, p=0.008), and smoking (OR 1.85, p=0.045) were independent predictors for significant coronary artery disease, but TSH level did not predict coronary artery stenosis. CONCLUSIONS: Although the high level of serum TSH is associated with multi-vessel disease, it was not the determinant of coronary artery disease in patients with normal range of thyroid function.

Aged↗

PubMed2006

Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: role of SIV-specific CD8+ T cell responses.

Previously, priming with replication-competent adenovirus-SIV multigenic vaccines and boosting with envelope subunits strongly protected 39% of rhesus macaques against rectal SIV(mac251) challenge. To evaluate protection durability, eleven of the protected and two SIV-infected unimmunized macaques that controlled viremia were re-challenged rectally with SIV(mac251). Strong protection was observed in 8/11 vaccinees, including two exhibiting <50 SIV RNA copies. Decreased viremia compared to naïve controls was observed in the other three. The SIV-infected unimmunized macaques modestly controlled viremia but exhibited CD4 counts < or =200, unlike the protected macaques. Durable protection was associated with significantly increased SIV-specific ELISPOT responses and lymphoproliferative responses to p27 at re-challenge. After CD8 depletion, 2 of 8 re-challenged, protected vaccinees maintained <50 SIV RNA copies; SIV RNA emerged in 6. Re-appearance of CD8 cells and restoration of SIV-specific cellular immunity coincided with viremia suppression. Overall, cellular immunity induced by vaccination and/or low-level, inapparent viremia post-first SIV(mac251) challenge, was associated with durable protection against re-challenge.

Adenoviridae↗

PubMed2006

Oral delivery of replication-competent adenovirus vectors is well tolerated by SIV- and SHIV-infected rhesus macaques.

Although replication-competent adenovirus (Ad) vectors are promising in AIDS vaccine design, their safety in immune compromised hosts is unknown. To initially address this question, enteric-coated tablets containing a replicating Ad vector were orally administered to SHIV- and SIV-infected rhesus macaques with normal, intermediate or low CD4 T cell counts and stable disease. The vector was detected within a week after tablet administration in stools of all animals but not in nasal secretions, indicating no spread of virus to the upper respiratory tract. CD4 T cell counts and viral loads remained stable in all animals and no signs of fever, weight loss, or other clinical symptoms of Ad-induced disease were observed during 10 weeks of follow-up. Oral delivery of the replicating Ad vector was safe and well tolerated by SHIV- and SIV-infected hosts. Oral enteric-coated tablets may prove safe for administering replicating Ad-vectored vaccines in areas with high HIV prevalence.

AIDS Vaccines↗

PubMed2006

Early up-regulation of CXC-chemokine expression is associated with strong cellular immune responses to murine skin xenografts.

BACKGROUND: The dynamic pattern of the cellular infiltration and mRNA expression of chemokines in rat-to-mouse skin xenografts were examined to gain an understanding of the possible role of chemokines in the stronger cellular immune responses to xenografts compared with the allo-response. METHODS: The mean survival time of the xenografts was approximately 2 days less than that of allografts (10.7 +/- 0.9 days vs. 8.9 +/- 0.7 days, P < 0.05). In comparison with the allografts, the xenografts were characterized by a very early infiltration of monocytes/macrophages (day 3) and a larger number of CD4+ and CD8+ cells, as well as neutrophil infiltration in the early phase (day 5), and larger number of CD8+ and CD11b+ cells, as well as macrophage infiltration, in the later phase (day 7). Xenografts showed stronger interferon (IFN)-inducible 10-kDa protein (IP-10) and monokine induced by IFN (MIG) mRNA expression levels, which appeared earlier than in the allografts. In the later phase, strong expression of regulated on activation, normal T cell expressed and secreted was observed. Cytokine mRNA expression in the xenografts could be summarized by higher expression of IFN-gamma, interleukin (IL)1beta, IL6, and transforming growth factor -beta1 mRNA than in the allografts. These results suggest that the early increased CXC-chemokine expression, such as IP-10 and MIG, which has been known to be mainly produced by macrophages, may play a critical role in the stronger cellular xenograft rejection compared with allograft rejection. Therefore, MIG antiserum or CXCR3 antiserum was administered to the rat skin-engrafted mice every other day until rejection. RESULTS: Compared with the control normal rabbit serum-treated mice, either the MIG antiserum- or CXCR3 antiserum-treated mice showed a delayed rejection of approximately 2 days (8.3 +/- 0.5 days vs. 10.6 +/- 0.5 days or 10.8 +/- 1.9 days, respectively, P < 0.05). CONCLUSION: Overall, these results suggest that the more aggressive rejection of xenografts compared with allografts is due to the earlier expression of CXC-chemokines, IP-10 and MIG, and subsequent adjuvant effects of proinflammatory cytokines.

Animals↗

PubMed2006

Development of a music group psychotherapy intervention for the primary prevention of adjustment difficulties in Korean adolescent girls.

PROBLEM: Traditionally, adolescent mental health in Korea has not been a prime focus for educators, health workers, and politicians, yet a majority of sampled adolescents report interpersonal sensitivity (Kim, 2003). METHOD: Thirty-five adolescent girls took part in a six-session school-based music group psychotherapy pilot intervention designed to promote relationships and improve self-control skills. FINDING: Participants identified several outcome benefits that may serve as protective factors in their continued social and emotional development. CONCLUSIONS: Music is a medium that promotes interpersonal relatedness among Korean adolescent girls. More research is necessary to identify long-term benefits of preventive music group psychotherapy interventions among the adolescent population.

Adjustment Disorders↗

PubMed2006

Clinical significance of aortic knob width and calcification in unstable angina.

BACKGROUND: Chest radiography is a routine examination evaluating those patients with chest pain. There are few data about the correlation between aortic knob width, calcification and coronary atherosclerosis. METHODS AND RESULTS: The aortic knob width was measured and the presence of aortic knob calcification was assessed via a chest posteroanterior view in 178 consecutive patients. The aortic knob width and calcification were compared to the risk factor and the extent of coronary artery disease. Patient's age (69.5+/-7.95 vs 61.1+/-10.29 years, p=0.010), the prevalence of hypertension (65.9 vs 46.3%, p=0.024) and diabetes (43.2 vs 26.1%, p=0.033), the level of total cholesterol (196.8+/-63.21 vs 188.6+/-44.45 mg/dl, p=0.049) and the incidence of multi-vessel disease (65.9 vs 38.1%, p<0.001) were higher in patients with aortic knob calcification than in patients without calcification. The aortic knob width and the prevalence of aortic knob calcification were significantly correlated with the severity of coronary artery disease. Multivariate analysis demonstrated that aortic knob calcification and diabetes were independent factors for multi-vessel disease (p=0.018 and p=0.012). CONCLUSIONS: The observation of aortic knob on a chest radiograph can provide important predictive information of coronary atherosclerosis.

Aged↗

PubMed2006

An increased monocyte count predicts coronary artery spasm in patients with resting chest pain and insignificant coronary artery stenosis.

BACKGROUND: Coronary atherosclerosis with inflammation gives rise to coronary vasospasm in the patients with coronary vasospastic angina. We have postulated that the peripheral leukocyte count and the differential count are associated with vasospastic angina. METHODS: 144 patients who underwent intracoronary ergonovine provocation testing between January 2002 and December 2004 were divided into two groups: Group I (72 patients with provoked spasm, mean age: 54.8 +/- 10.7 years, males: 75%) and Group II (72 without spasm, mean age: 55.3 +/- 10.2 years, males: 35%). Blood sampling was done to measure the lipid profiles and inflammatory markers, including the high sensitive C-reactive protein (hsCRP) levels and the monocyte counts. We compared the angiographic findings and laboratory data between the two groups. RESULTS: There were no significant differences in the levels of serum lipid and hsCRP between the two groups. The white blood cell count and the monocyte count were higher in Group I than with Group II (7496.4 +/- 2622.28 vs. 6703.2 +/- 1768.37/mm3, respectively, p = 0.035; 627.5 +/- 270.70 vs. 426.9 +/- 205.76/mm3, respectively, p < 0.001). Gensini's score was higher in Group I than in Group II (2.2 +/- 2.88 vs. 0.5 +/- 1.03, respectively, p < 0.001). Multivariate analysis showed that the monocyte count and Gensini's score were independent factors affecting coronary spasm (p = 0.047 and p = 0.018, respectively). According to a receiver operating characteristics curve analysis, the area under the curve of the monocyte count was 0.738, that of the neutrophil count was 0.577 and that of the WBC count was 0.572. The cut-off value of the monocyte count was 530/mm3; the sensitivity and specificity of this cut-off value were 64% and 76%, respectively. CONCLUSIONS: The peripheral monocyte count is an independent marker for predicting vasospastic angina in the patients with resting chest pain and insignificant coronary artery stenosis.

Adult↗

PubMed2005

Down-regulation of MHC class I expression in human neuronal stem cells using viral stealth mechanism.

Due to their unique capacity for self-renewal in addition to their ability to differentiate into cells of all neuronal lineages, neuronal stem cells (NSCs) are promising candidates for cell replacement therapy in neuronal injury and neurodegenerative diseases. However, there are few studies on immune rejection, which is one of the main problems facing successful stem cell therapy. In order to determine if human NSC might be rejected after transplantation the MHC expression level was examined in the HB1.F3 cell line, which has previously been shown to exhibit NSC properties. The results showed low expression levels of the MHC class I molecules on the surfaces of these cells. A dramatic increase in the MHC class I expression level was observed when the cells were treated with IFN-gamma, TNF-alpha, and IL-1beta, alone or in combination. The maximum induction of MHC class I protein expression was observed at above 20ng/ml IFN-gamma 48h after the treatment. The apparent additive effects of TNF-alpha and IL-1beta in combination on the maximum induction of MHC class I expression exerted by IFN-gamma treatment were not observed. The MHC class I levels elevated by IFN-gamma were sustained for 72h after withdrawing the IFN-gamma. Therefore, this study introduced human cytomegalovirus (hCMV) US genes, which are known to be able to reduce the MHC class I expression level on the cell surface after infection, into HB1.F3 cells. The cells transfected with the hCMV US2, US3, US6 or US11 genes showed 20-50% reduction in the MHC class I expression level compared with the mock-transfected cells. These results suggest that NSC expresses high levels of the MHC class I proteins, and unless they are modified, might be rejected upon transplantation. In addition, the various viral stealth mechanisms can be exploited for stem cell transplantation.

Cell Line↗

PubMed2005

Silanimonas lenta gen. nov., sp. nov., a slightly thermophilic and alkaliphilic gammaproteobacterium isolated from a hot spring.

A moderately thermophilic aerobic bacterium, strain 25-4T, was isolated from a hot spring at Baekdoo Mountain in Korea. The cells were Gram-negative, motile rods each having a polar flagellum. Analysis of the 16S rRNA gene sequence indicated that the strain represented a new lineage within the family 'Xanthomonadaceae' of the 'Gammaproteobacteria', being most closely related to the genera Thermomonas, Xanthomonas, Luteimonas, Pseudoxanthomonas, Stenotrophomonas and Xylella and having 16S rRNA gene sequence similarities to the most related species of the genera of between 92.9 and 94.4 %. The strain contained Q-8 as the major isoprenoid quinone and had a fatty acid profile with predominant iso-branched fatty acids. Growth occurred at pH 6.0-10, with an optimum at pH 9.0, and at 25-53 degrees C, with an optimum at 47 degrees C. The G+C content of the genomic DNA was 50.7 mol%. On the basis of phylogenetic analyses and its phenotypic characteristics, strain 25-4T belongs to a new genus, Silanimonas gen. nov., within the 'Gammaproteobacteria'. The sole species of this genus is Silanimonas lenta sp. nov. (type strain, 25-4T=DSM 16282T=KCTC 12236T).

Bacterial Typing Techniques↗

PubMed2004

Multi-analyte single-membrane biosensor for the serotype-specific detection of Dengue virus.

A multi-analyte biosensor based on nucleic acid hybridization and liposome signal amplification was developed for the rapid serotype-specific detection of Dengue virus. After RNA amplification, detection of Dengue virus specific serotypes can be accomplished using a single analysis within 25 min. The multi-analyte biosensor is based on single-analyte assays (see Baeumner et al (2002) Anal Chem 74:1442-1448) developed earlier in which four analyses were required for specific serotype identification of Dengue virus samples. The multi-analyte biosensor employs generic and serotype-specific DNA probes, which hybridize with Dengue RNA that is amplified by the isothermal nucleic acid sequence based amplification (NASBA) reaction. The generic probe (reporter probe) is coupled to dye-entrapping liposomes and can hybridize to all four Dengue serotypes, while the serotype-specific probes (capture probes) are immobilized through biotin-streptavidin interaction on the surface of a polyethersulfone membrane strip in separate locations. A mixture of amplified Dengue virus RNA sequences and liposomes is applied to the membrane and allowed to migrate up along the test strip. After the liposome-target sequence complexes hybridize to the specific probes immobilized in the capture zones of the membrane strip, the Dengue serotype present in the sample can be determined. The amount of liposomes immobilized in the various capture zones directly correlates to the amount of viral RNA in the sample and can be quantified by a portable reflectometer. The specific arrangement of the capture zones and the use of unlabeled oligonucleotides (cold probes) enabled us to dramatically reduce the cross-reactivity of Dengue virus serotypes. Therefore, a single biosensor can be used to detect the exact Dengue serotype present in the sample. In addition, the biosensor can simultaneously detect two serotypes and so it is useful for the identification of possible concurrent infections found in clinical samples. The various biosensor components have been optimized with respect to specificity and sensitivity, and the system has been ultimately tested using blind coded samples. The biosensor demonstrated 92% reliability in Dengue serotype determination. Following isothermal amplification of the target sequences, the biosensor had a detection limit of 50 RNA molecules for serotype 2, 500 RNA molecules for serotypes 3 and 4, and 50,000 molecules for serotype 1. The multi-analyte biosensor is portable, inexpensive, and very easy to use and represents an alternative to current detection methods coupled with nucleic acid amplification reactions such as electrochemiluminescence, or those based on more expensive and time consuming methods such as ELISA or tissue culture.

Biosensing Techniques↗

PubMed2004

Targeted gene disruption of the heat shock protein 72 gene (hsp70.1) in the donor tissue is associated with a prolonged rejection-free survival in the murine skin allograft model.

It is known that the expression level of the heat shock protein (HSP) is elevated in allograft tissues, but the specific role of the HSP in the acute rejection has not been elucidated. This study aims to determine how and when the HSP72 molecule works immunologically in the process of acute allograft rejection from a skin graft model in which HSP72 (hsp70.1 gene) knock out (KO) mice were adopted either as a donor or as a recipient. In experiment I, tail skin was grafted from either the HSP72 KO C57BL/6 mice or wild-type C57BL/6 mice--as the allograft control--onto the trunk of B10BR mice. The grafts were observed for any signs of rejection until the 14th day after the graft. The survival of the grafted skin from the two donor groups was analyzed by a log-rank method. The grafted skin was observed for the degree of rejection using light microscopy. In addition, the degree of apoptosis was assessed using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). A mixed lymphocyte reaction (MLR) was observed with HSP72 KO C57BL/6 splenocytes as the stimulator and B10BR mice lymphocytes as the responder cells. The cytokine levels, such as interleukin-2 (IL-2) and interferon-gamma, were measured from an MLR supernatant using enzyme-linked immunosorbent assay (ELISA). In experiment II, the tail skin was grafted in the opposite direction from the B10BR mice to the HSP72 KO or wild-type C57BL/6 mice, and the grafts were observed for any signs of rejection, as defined in experiment I. The absence of HSP72 expression was observed in the HSP72 KO mice lymphocytes after heat stress (42 degrees C) using Western blot analysis. In experiment I, the survival of the skin grafts from the HSP72 KO C57BL/6 mice was 12+/-1.3 days (median+/-S.E.), which was significantly longer than that from the allograft control donor (9+/-0.6 days; p=0.03). This coincided with the microscopic finding of the graft tissues. The MLR response of the CD4+ lymphocytes stimulated by HSP72 KO C57BL/6 splenocytes was lower, and the interferon-gamma concentration from the MLR supernatant was also lower. On Day 9, 3.7+/-1.1(mean+/-S.D.) TUNEL-positive cells per unit high-power field (HPF) were observed from the HSP72 KO C57BL/6 skin, which was significantly lower than that from the control skin (8.7+/-2.1 cells/HPF; p=0.045). In contrast, in experiment II, there was no difference in the survival of the skin graft either from the B10BR to HSP72 KO C57BL/6 mice or from the B10BR to the wild-type C57BL/6 mice. In summary, the survival of the skin grafts from the HSP72 KO C57BL/6 mice was prolonged, and the degree of rejection was lower than that from the allograft control. This means that the presence of HSP72 in the donor tissue is related to the up-regulation of acute rejection from the recipient immune system. The HSP72 KO mice as the donor were shown to have decreased level of antigen presentation to the recipient CD4+ lymphocytes. Therefore, the HSP72 molecule from the donor cells is believed to be related to the induction of the recipient immune reaction via alloantigen presentation.

Animals↗

PubMed2002

Biosensor for dengue virus detection: sensitive, rapid, and serotype specific.

A serotype-specific RNA biosensor was developed for the rapid detection of Dengue virus (serotypes 1-4) in blood samples. After RNA amplification, the biosensor allows the rapid detection of Dengue virus RNA in only 15 min. In addition, the biosensor is portable, inexpensive, and very easy to use, making it an ideal detection system for point-of-care and field applications. The biosensor is coupled to the isothermal nucleic acid sequence-based amplification (NASBA) technique with which small amounts of virus RNA are amplified using a simple water bath. During the NASBA reaction, a generic sequence is attached to all RNA molecules as described earlier (Wu, S. J.; Lee, E. M.; Putvatana, R.; Shurtliff, R. N.; Porter, K R.; Suharyono, W.; Watt, D. M.; King, C. C.; Murphy, G. S.; Hayes, C. G.; Romano, J. W. J. Clin. Microbiol. 2001, 39, 2794-2798.). It has been shown earlier that Dengue virus can be detected specifically using two DNA probes: a first probe hybridized with the attached generic sequence and, therefore, bound to every amplified RNA molecule; and a second probe either bound to all four Dengue virus serotypes or chosen to be specific for only one serotype. These probes were utilized in the biosensor described in this publication. For a generic Dengue virus biosensor, the second probe is complementary to a conserved region found in all Dengue serotypes. For identification of the individual Dengue virus serotypes, four serotype-specific probes were developed (Wu, S. J.; Lee, E. M.; Putvatana, R.; Shurtiff, R. N.; Porter, K. R.; Suharyono, W.; Watt, D. M.; King, C. C.; Murphy, G. S.; Hayes, C. G.; Romano, J. W. J. Clin. Microbiol. 2001, 39, 2794-2798.). The biosensor is a membrane-based DNA/RNA hybridization system using liposome amplification. The generic DNA probe (reporter probe) is coupled to the outside of dye-encapsulating liposomes. The conserved or Dengue serotype specific probes (capture probes) are immobilized on a polyethersulfone membrane strip. Liposomes are mixed with amplified target sequence and are then applied to the membrane. The mixture is allowed to migrate along the test strip, and the liposome-target sequence complexes are immobilized in the capture zone via hybridization of the capture probe with target sequence. The amount of liposomes present in the immobilized complex is directly proportional to the amount of target sequence present in the sample and can be quantified using a portable reflectometer. The different biosensor components have been optimized with respect to sensitivity and, foremost, specificity toward the different serotypes. An excellent correlation to a laboratory-based detection system was demonstrated. Finally, the assay was tested using a limited number of clinical human serum samples. Although Dengue serotypes 1, 2 and 4 were identified correctly, serotype 3 displayed low cross-reactivity with biosensors designed for detection of serotypes 1 and 4.

Animals↗

PubMedDate not supplied

Inducible nitric oxide synthase inhibitors prolonged the survival of skin xenografts through selective down-regulation of pro-inflammatory cytokine and CC-chemokine expressions.

To elucidate the possible immunoregulatory role of nitric oxide (NO) in cellular xenograft rejection we performed rat-to-mouse skin xenotransplantation. The rat skin engrafted mice were treated with the inducible NO synthase (iNOS) inhibitors, aminoguanidine (AMG, 200 mg/kg) and NG-nitro-L-arginine methyl ester (L-NAME, 60 mg/kg) every other day until rejection. Skin xenograft survival was monitored and immune cell infiltration and intragraft cytokine and chemokine mRNA expressions were analyzed 7 days after grafting. Compared with the control mice, the AMG- and L-NAME treated mice showed delayed xenograft rejection by approximately 3 days (8.9 +/- 0.7 days vs. 11.7 +/- 1.2 and 12.0 +/- 0.9 days, respectively). Infiltrations of CD11b+, MOMA-2+ cells and neutrophils were significantly reduced in both AMG- and L-NAME treated graft but CD4+ and CD8+ cells were not. The expression of cytokines such as IL-1beta, IL-2, IL-6, IL-12 and IFN-gamma in AMG- and L-NAME treated grafts were significantly decreased (P<0.01), whereas IL-10, TNF-alpha and TGF-beta1 were unchanged or enhanced. Additionally, the expressions of CC-chemokines, such as RANTES and MIP-1alpha, were significantly reduced (P<0.01) whereas the expressions of CXC-chemokines, such as IP-10 and MIG, were unchanged. These results imply that prolonged rat-to-mouse skin xenograft survival by iNOS inhibitors may be due to the selective inhibition of pro-inflammatory cytokines and chemokines and suggest the possible regulatory role of NO in cytokine and chemokine expressions during xenotransplant rejection.

Animals↗