Biomedical subjects

Bo Lin

Publications and source records attributed to Bo Lin.

At least 19 recordsLinked to original sources

PubMed2026

Spatiotemporal mapping of tertiary lymphoid structure heterogeneity shapes immune niches and clinical outcomes in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy with limited therapeutic options. The spatial architecture and functional diversity of tertiary lymphoid structures (TLSs) in iCCA remain unclear. Here, we present a multimodal spatial atlas of TLSs and identified intratumoral TLSs (iTLSs) as independent prognostic markers. Bulk proteomic profiling of 214 discovery and 155 validation cases identified a four-tier TLS-based tumor microenvironment classification system and supported development of a TLS-predictive random forest classifier. Imaging mass cytometry revealed that iTLS+ tumors harbor structured immune architectures, where M1-like tissue-resident macrophages (RTMs), dendritic cells, and CXCL13+ CD4+ T cells colocalize to form antigen-presenting neighborhoods (apc-CNs) spatially coupled to TLS core regions (TLScore-CNs). Single-cell spatial transcriptomics further resolved 61 TLSs into 14 spatial niches and defined a pseudotemporal maturation continuum: aggregated, activated, and postactivated. Intraniche communication, primarily mediated by ifnCAFs, iCAFs, and CXCL12+ macrophages, evolved dynamically with maturation. Single-nucleus RNA sequencing combined with Tangram-based spatial mapping revealed CXCL12+ macrophages and iCAFs forming a peripheral band in aggregated TLSs, whereas ifnCAFs infiltrated TLS interiors during activation. These findings define TLS heterogeneity and provide insights for stroma-directed immunotherapy.

Cholangiocarcinoma↗

PubMed2006

A PI3K pathway mediates hair cell survival and opposes gentamicin toxicity in neonatal rat organ of Corti.

Gentamicin is well known to promote hair cell death in inner ear, but it also appears to activate opposing pathways that promote hair cell survival. In combination with others, our previous work has indicated that a K-Ras/Rac/JNK pathway is important for hair cell death and an H-Ras/Raf/MEK/Erk pathway is involved in promoting hair cell survival (Battaglia et al., Neuroscience 122(4):1025-1035, 2003). However, these data also suggested that a Ras-independent survival pathway for activation of MEK might be stimulated by gentamicin. To investigate alternatives to the Ras/Raf/MEK/Erk pathway in promoting hair cell survival, cochlear explants were exposed to gentamicin combined with several inhibitors of alternative pathways (LY294002, calphostin C, SH-6, U73122). When exposed to gentamicin with the PI3K inhibitor LY294002 (10, 50 microM), the protein kinase C (PKC) inhibitor calphostin C (50, 100 nM) or the PKB/Akt inhibitor SH-6 (5, 10 microM), hair cell damage was significantly increased compared to gentamicin alone. By Western blotting, strong PKB/Akt activation was observed in the organ of Corti following exposure to 50 microM gentamicin for 6 h. In addition, PKC activation by 12-O-tetradecanoylphorbol-13-acetate protected outer hair cells from gentamicin induced cell death. In contrast, the phospholipase C-gamma (PLCgamma) inhibitor U73122 (2, 5 microM) did not affect hair cell damage when combined with gentamicin. Also, phosphorylation of PLCgamma was not increased in the organ of Corti following gentamicin treatment, as evaluated by Western blot. The results indicate that PI3K promotes hair cell survival via its downstream targets, PKC and PKB/Akt. This suggests that both Ras-dependent and Ras-independent survival pathways are involved during gentamicin exposure. In contrast, PLCgamma activation of PKC does not appear to play a role.

Animals↗

PubMed2006

Activin modulates the transcriptional response of LbetaT2 cells to gonadotropin-releasing hormone and alters cellular proliferation.

Both GnRH and activin are crucial for the correct function of pituitary gonadotrope cells. GnRH regulates LH and FSH synthesis and secretion and gonadotrope proliferation, whereas activin is essential for expression of FSH. Little is known, however, about the interplay of signaling downstream of these two hormones. In this study, we undertook expression profiling to determine how activin pretreatment alters the transcriptional response of LbetaT2 gonadotrope cells to GnRH stimulation. Activin treatment alone altered the transcriptional profile of 303 genes including inducing that of the 17beta-hydroxysteroid dehydrogenase B1 gene that converts estrone to 17beta-estradiol, altering the sensitivity of the cells to estrone. Furthermore, activin had a dramatic effect on the response of LbetaT2 cells to GnRH. Hierarchical clustering of 2453 GnRH-responsive genes identified groups of genes the response of which to GnRH was either enhanced or blunted after activin treatment. Mapping of these genes to gene ontology classifications or signaling pathways highlighted significant differences in the classes of altered genes. In the presence of activin, GnRH regulates genes in pathways controlling cell energetics, cytoskeletal rearrangements, organelle organization, and mitosis in the absence of activin, but genes controlling protein processing, cell differentiation, and secretion. Therefore, we demonstrated that activin enhanced GnRH induction of p38MAPK activity, caused GnRH-dependent phosphorylation of p53, and reduced the ability of GnRH to cause G1 arrest. Thus, although activin alone changes a modest number of transcripts, activin pretreatment dramatically alters the response to GnRH from an antiproliferative response to a more differentiated, synthetic response appropriate for a secretory cell.

Activins↗

PubMed2006

Determination of fluoroquinolones in eggs using in-tube solid-phase microextraction coupled to high-performance liquid chromatography.

A simple, rapid, and sensitive method using in-tube solid-phase microextraction (in-tube SPME) based on poly(methacrylic acid-ethylene glycol dimethacrylate) (MAA-EGDMA) monolith coupled to HPLC with fluorescence and UV detection was developed for the determination of five fluoroquinolones (FQs). Ofloxacin (OFL), norfloxacin (NOR), ciprofloxacin (CIP), enrofloxacin (ENRO), and sarafloxacin (SARA) can be enriched and determined in the spiked eggs and albumins. CIP/ENRO in eggs and albumins of ENRO-treated hens were also studied using the proposed method. Only homogenization, dilution, and centrifugation were required before the sample was supplied to the in-tube microextraction, and no organic solvents were consumed in the procedures. Under the optimized extraction conditions, good extraction efficiency for the five FQs was obtained with no matrix interference in the process of extraction and the subsequent chromatographic separation. The detection limits (S/N=3) were found to be 0.1-2.6 ng g(-1) and 0.2-2.4 ng g(-1) in whole egg and egg albumin, respectively. Good linearity could be achieved over the range 2-500 ng mL(-1) for the five FQs with regression coefficients above 0.9995 in both whole egg and albumin. The reproducibility of the method was evaluated at three concentration levels, with the resulting relative standard deviations (RSDs) less than 7%. The method was successfully applied to the analysis of ENRO and its primary metabolite CIP in the eggs and albumins of ENRO-treated hens.

Albumins↗

PubMed2006

Perphenylcarbamoylated beta-cyclodextrin bonded-silica particles as chiral stationary phase for enantioseparation by pressure-assisted capillary electrochromatography.

Perphenylcarbamoylated beta-cyclodextrin bonded-silica particles (5 microm) were packed into 75-mum fused-silica capillaries, and used for the enantiomer separation of neutral and basic solutes by pressure-assisted capillary electrochromatography. Triethylammonium acetate and phosphate buffer were employed as the BGEs. A cathodic EOF was observed with these two BGEs. Seven chiral analytes were successfully resolved into their enantiomers under optimized conditions, and five of them could be baseline-separated within 12 min due to their high electrophoretic mobility. Better results were achieved with phosphate buffer as the BGE. The effects of organic content and pH on the enantioseparation were also investigated.

Buffers↗

PubMed2006

HPLC separation of fullerenes on two charge-transfer stationary phases.

Two charge-transfer stationary phases were prepared by immobilizing p-nitrobenzoic acid and naphthyl acetic acid onto silica. The nitrophenyl moiety and the naphthyl moiety were grafted to silica gel through the spacer of aminoalkyl silanes. The HPLC separation of C60, C70, and higher fullerenes on the new stationary phases was also studied. The influence of mobile phase and column temperature on the separation of C60 and C70 was examined, respectively. The retentions of C60 and C70 on the two stationary phases increased with decreasing toluene content in the mobile phase or with increasing column temperature. Higher fullerenes can be separated well using toluene as the mobile phase on the stationary phase of p-nitrobenzoic acid-bonded silica.

Journal Article↗

PubMed2005

Preparation of pyrenebutyric acid bonded silica stationary phases for the application to the separation of fullerenes.

A novel immobilization method was proposed for the preparation of pyrenebutyric acid-bonded silica (PYB-silica) stationary phases. The pyrene moiety was grafted to silica gel through spacers of aminoalkyl silanes. The HPLC separation of C60, C70 and higher fullerenes on the new pyrenebutyric acid-bonded silica stationary phases was also studied. Based on the temperature effect, the intermolecular interaction between stationary phases and solutes and the retention mechanism were discussed. The results of column loading capacity test demonstrated the potential for the separation of fullerenes in large amounts on the PYB-silica stationary phases.

Chromatography, High Pressure Liquid↗

PubMed2005

CMV-hFasL transgenic mice prevent from experimental autoimmune thyroiditis.

BACKGROUND: Previous studies showed that the role of Fas ligand (FasL) is not consistent in the pathogenesis of autoimmune thyroiditis. This study was designed to investigate the effects of FasL on the pathogenesis of experimental autoimmune thyroiditis (EAT) using CMV-human FasL (hFasL) transgenic mice. METHODS: Transgenic mice ubiquitously expressing hFasL were used as an animal model of EAT by injection of porcine thyroglobulin (pTg). Expression of hFasL was detected by RT-PCR and Western blot. The activity of hFasL transgenic thyrocytes killing Jurket cells was determined. CMV-hFasL transgenic mice and wild type (WT) mice were immunized with pTg and killed 28 days later to evaluate the lymphocytic infiltration of their thyroids. The number of CD4+ and CD8+ lymphocytes from the spleen was detected using FACS. The serum interferon-gamma (IFN-gamma) concentration was measured by ELISA. RESULTS: hFasL expression in the thyroid of CMV-hFasL transgenic mice was confirmed. After co-incubation of Jurket thymocytes with thyroid tissues of CMV-hFasL transgenic mice, the percentage of apoptotic cells in the CMV-hFasL transgenic thyroid group was significantly higher than that of the control WT thyroid group [(23.4 +/- 4.3)% vs (6.6 +/- 2.5)%, P < 0.01]. On day 28 after immunization with pTg, the infiltration index of lymphocytes in thyroids of the CMV-hFasL transgenic mice was significantly lower than that of the WT mice [(1.0 +/- 0.5) vs (2.1 +/- 0.7), P < 0.001]. Moreover, the number of CD4+ and CD8+ lymphocytes of the spleen and serum IFN-gamma concentration were significantly decreased in the CMV-hFasL transgenic mice. CONCLUSIONS: FasL plays an important role in the pathogenesis of autoimmune thyroiditis. Transgenic mice ubiquitously expressing hFasL may strongly inhibit lymphocytic infiltration of the thyroid of EAT and ameliorate the course of this disease.

Animals↗

PubMed2005

[Physiological responses of 2-year-old Acer davidii seedings to short-term enhanced UV-B radiation].

At the Maoxian Ecological Experimental Station of Chinese Academy of Sciences in northwest Sichuan Province, 2-year-old native maple(Acer davidii) seedlings were potted outdoors with enhanced UV-B radiation(280 - 320 nm) of 0.27 W x m(-2) (7.7 kJ x m(-2) x d(-1)), which was approximated to the predicted enhanced UV-B reaching the earth surface when stratosphere ozone was depleted by 15% in the local area, with the control plant received ambient UV-B. The gas exchange index and chlorophyll fluorescence, and the contents of chlorophyll and UV-absorbing compounds were examined after 50 days of the radiation. The results showed that enhanced UV-B radiation significantly lowered the maximal net photosynthetic rate (CK = 6.214, TR = 4.452), raised the dark respiration rate(CK = 0.413, TR = 1.295) and light compensation point (CK = 21.629, TR = 59.861), but had little effect on quantum yield (CK = 0.021, TR = 0.032). Under enhanced UV-B radiation, the diurnal changes in net photosynthetic rate, water use efficiency, quantum efficiency of photosystem II centers (Fv/Fm), and quantum yield of photosystem II photochemistry (phi(pspi)) were reduced, chlorophyll a, total chlorophylls, and chlorophyll a/b (CK= 16.23, 5.39, TR = 13.17, 4.93) were also markedly reduced, but chlorophyll b remained nearly unchanged. Contrary to the previous studies, enhanced UV-B radiation decreased the content of UV-absorbing compounds (CK = 0.87, TR = 0.79) in 2-year-old Acer davidii seedling leaves, indicating that the measurement of leaf UV-B absorbing compounds didn't necessarily provide a good indicator of plant tolerance to UV-B. It could be concluded that enhanced UV-B radiation had some inhibitory effects on the photosynthesis of Acer davidii seedlings. Long-term researches are necessary to confirm this conclusion.

Acer↗

PubMed2004

Label-free assays on the BIND system.

Screening of biochemical interactions becomes simpler, less expensive, and more accurate when labels, such as fluorescent dyes, radioactive markers, and colorimetric reactions, are not required to quantify detected material. SRU Biosystems has developed a biosensor technology that is manufactured on continuous sheets of plastic film and incorporated into standard microplates and microarray slides to enable label-free assays to be performed with high throughput, high sensitivity, and low cost per assay. The biosensor incorporates a narrow band guided-mode resonance reflectance filter, in which the reflected color is modulated by the attachment/detachment of biochemical material to the surface. The technology offers 4 orders of linear dynamic range and uniformity within a plate, with a coefficient of variation of 2.5%. Using conventional biochemical immobilization surface chemistries, a wide range of assay applications are enabled. Small molecule screening, cell proliferation/cytotoxicity, enzyme activity screening, protein-protein interaction, and cell membrane receptor expression are among the applications demonstrated.

Animals↗

PubMed2004

Direct transfer of A20 gene into pancreas protected mice from streptozotocin-induced diabetes.

AIM: To investigate the efficiency of transfer of A20 gene into pancreas against STZ-induced diabetes. METHODS: PVP-plasmid mixture was directly transferred into the pancreatic parenchyma 2 d before STZ injection. The uptake of plasmid pcDNA3-LacZ or pcDNA3-A20 was detected by PCR and the expression of LacZ was confirmed by histological analysis with X-gal. A20 expression in the pancreas of pcDNA3-A20 transgenic mice was measured by RT-PCR and Western blots. Urine amylase, NO generation, and histological examination were examined. RESULTS: Injection of PVP-plasmid mixture directly into the pancreatic parenchyma increased urine amylase concentration 16 h after operation and reversed it to nearly normal 36 h later. On d 33 LacZ expression could be found in spleen, duodenum, and islets. The development of diabetes was prevented by direct A20 gene transferring into the pancreas and A20-mediated protection was correlated with suppression of NO production. The insulitis was ameliorated in A20-treated mice. CONCLUSION: Injection of PVP-plasmid mixture directly into the pancreatic parenchyma led to target gene expression in islets. Direct transfer of A20 gene into the pancreas protected mice from STZ-induced diabetes.

Amylases↗

PubMed2004

[Influence of FasL overexpression in transgenic mice on the immune regulative function of Sertoli cell].

AIM: To study the influence of FasL overexpression in transgenic mice on the Sertoli cell immune response to testicular infection. METHODS: Ureaplasma urealyticum (UU) was directly injected into bladders of FasL transgenic mice and wild-type mice respectively, to mimic an ascending infection pathway. At week 1, 2 and 3 after injection, respectively, the mice were put to death to observe the pathological alterations in testis section. And at the same time the differences of FasL, TGF-beta, IL-1alpha and IL-6 expressions on Sertoli cells were compared by immunohistochemical staining between wild mice and transgenic mice before and after infection, respectively. The high-purified Sertoli cells were isolated from the testis tissue of wild-type mice, comparing apoptotic capability of Fas(+) Jurkat cells mediated by FasL(+) Sertoli cells of wild control and wild UU-infected groups. RESULTS: The pathological changes of testis tissue from transgenic mice were more serious as compared with wild-type mice and the model of cytokines secreted by sertoli cells was distinctive between the two kinds of mice. The UU-infected Sertoli cells increased Fas(+) Jurkat cell apoptosis. CONCLUSION: FasL overexpression can influence the cytokine's secretion in the process of anti-infection immunity and further affects the immune balance of testis locality. Not all FasL over expression is benefit to body's anti-infection immune response.

Animals↗

PubMed2004

[Dynamics of biomass and stem volume of Picea asperata stands in artificial restoration process of subalpine coniferous forest].

The dynamics of aboveground biomass and stem volume in subalpine coniferous Picea asperata plantations with different stand ages in 70 years of artificial restoration process were studied by adopting the concept of space as a substitute for time. The results indicated that before 20 years of stand age, the biomass of spruce single tree grew quite slow, with that of the twigs and needles accounting for about 50%; after 20 years, it increased obviously, with 60% of biomass accumulated in stem; from 30 to 40 years, the increasing rate of biomass relatively slowed down, and maintained a rapid growth after 40 years. The biomass of spruce population showed a similar trend, though the period of relative slow-down of growth continued from 30 to 50 years. For the biomass of community as a whole, it presented a general continuous increase, but varied greatly for different layers. In shrub layer, the biomass rose rapidly at the early stage of plantation establishment and gradually decreased after 20 years, while that of the herbaceous plants reduced continuously and accounted less than 0.2% of the total biomass of community when the stand reached 70 years. Both the mean annual increment and the current annual increment of stem volume of spruce single tree went up with the increasing stand age, and more rapidly at the later stages. Similar changes were observed for the stock volume of the plantations, with the only difference that the current annual increment from 30 to 50 years was relatively reduced. Based on the data from stem analysis and growth ring measurement, regression models of stem volume with DBH and tree height of 70 years Picea asperata plantation were established.

Biomass↗

PubMed2004

[Dynamics of species diversity in artificial restoration process of subalpine coniferous forest].

Through plot investigation and by adopting the concept of space as a substitute for time, the developments of species diversity of trees, shrubs and herbaceous plants in subalpine coniferous plantations at different restoration stages were studied, and the correlation coefficients of species in each layer were discussed. The results indicated that in the restoration process, the species richness, diversity and evenness in subalpine coniferous plantations were gradually increased in a fluctuating way. The restoration process of Picea asperata plantations showed a tendency of development that in favor of resuming species diversity. The indices of species richness (species number and Margalef index) and species diversity (Shannon-Wiener index and Simpson index) of trees increased rapidly from the early stages of plantation establishment to the stage of canopy closing (about 30 yr of stand age) and then presented a tendency of decrease with some slight fluctuations, while the index of species evenness showed a periodical rising trend. For the shrub layer, the indices of species richness (Simpson index and Macintosh index) gradually increased with increasing restoration years, whereas the indices of species diversity (Shannon-Wiener index) decreased in the early stages, sharply increased during the stages of canopy closing, and then slowly decreased, which exhibited a tendency of high-->low-->high. In the layer of herbaceous plants, the indices of species richness (Margalef index and number of species) and species diversity (Simpson index, Macintosh index and Shannon-Wiener index) presented a trend of decrease in the early stages of plantations establishment to canopy closing and increased later on. During this process, herbaceous species and their life forms changed greatly, with shade tolerant species gradually substituting the intolerant species. Among the plantations of different stand ages, the average correlation coefficients of trees, shrubs and herbaceous species were 41.88%, 50.61% and 37.22%, respectively, indicating that in the 70 years of artificial forest restoration, the continuity and stability of shrub species were the highest, those of herbaceous species showed greatest fluctuation because of the disappearance and regeneration occurred with the alteration of the environmental conditions of plantations, and those of the trees were intermediary.

Altitude↗

PubMed2004

[Dynamics of litters in artificial restoration process of subalpine coniferous forest].

By adopting the concept of space as a substitute for time and taking the primitive subalpine coniferous forests as a reference, this paper investigated the forest litters in 10, 30, 40, 50 and 60-years subalpine Picea asperata stands to study the development process of litters in subalpine coniferous plantations with different restoration stages. The difference in litter development in artificial and natural stands was also discussed. The results indicated that in Picea asperata plantations with different ages, the litter pool on forest floor and the nutrient storage and maximum moisture holding capacity of litters showed a general trend of decrease at their earlier restoration stages, and of increase at the later stages. The trend of increase reached the maximum around 50 years of restoration, and then gradually leveled off or even slightly decreased. The observed litter pool (70.21 x 10(3) kg x hm(-2)), nutrient storage (4.73 x 10(3) kg x hm(-2)) and maximum moisture holding capacity (89.98 x 10(3) kg x hm(-2)) of 60-years plantations were considerably small, only accounted for 48.40%, 46.79% and 46.99% of the primitive forests, respectively. After 40 years of restoration, both artificial stands and naturally regenerated secondary forests showed similarity in litter dynamics, annual litterfall, and amount of annual nutrient returning to the soils, while a big difference in litter components, litter pool and structure on the forest floor, nutrient storage, and maximum moisture holding capacity. The difference which accounts for the difference in ecological functioning of the subalpine coniferous plantations lagging behind that of the secondary forests might be mainly caused by the less species diversity of the former.

Biodiversity↗

PubMed2004

[Effects of light and temperature on seed germination of Picea asperata and Betula albo-sinensis].

The effects of different light and temperature conditions on seed germination of two keystone species (Picea asperata and Betula albo-sinensis) in subalpine coniferous forests were studied by simulating environmental conditions in climatic chambers. The results indicated that the optimal temperature of seed germination for both species was 25 degrees C, with the germination rate of 88.8 +/- 8.4% and 30.8 +/- 10.4%, respectively. Through multiple comparisons with Tukey's HSD, B. albo-sinensis was more sensitive to temperature than P. asperata. Seeds of P. asperata could germinate when the temperature reached 10 degrees C, but those of B. albo-sinensis could not, which implied that the latter as a pioneer species of subalpine coniferous forest areas needed higher lowest temperature for seed germination. Day and night temperature difference (15 degreesC/10 degrees C, 20 degrees C/15 degrees C and 20 degrees C/10 degrees C) had significant effect on the germination rates of tested seeds, which was the highest under 20 degrees C/15 degrees C. A wide range of day and night temperature difference seemed to be unfavorable to the seed germination of B. albo-sinensis. Light intensity also had a marked effect on the germination rates of test seeds. Under 20% transmittance, the germination rate of P. asperata and B. albo-sinensis was the highest, being 83.0 +/- 6.6% and 29.2 +/- 5.5%, respectively, and the initiation time and regularity of germination were the best as well. Furthermore, B. albo-sinensis was less sensitive to light than P. asperata, which was determined by the life behavior of tree itself.

Betula↗

PubMed2003

Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay.

Respiratory syncytial virus (RSV) is a ubiquitous human pathogen and the leading cause of lower respiratory tract infections in infants. Infection of cells and subsequent formation of syncytia occur through membrane fusion mediated by the RSV fusion protein (RSV-F). A novel in vitro assay of recombinant RSV-F function has been devised and used to characterize a number of escape mutants for three known inhibitors of RSV-F that have been isolated. Homology modeling of the RSV-F structure has been carried out on the basis of a chimera derived from the crystal structures of the RSV-F core and a fragment from the orthologous fusion protein from Newcastle disease virus (NDV). The structure correlates well with the appearance of RSV-F in electron micrographs, and the residues identified as contributing to specific binding sites for several monoclonal antibodies are arranged in appropriate solvent-accessible clusters. The positions of the characterized resistance mutants in the model structure identify two promising regions for the design of fusion inhibitors.

Amino Acid Sequence↗

PubMed2003

Intramuscular injection of interleukin-10 plasmid DNA prevented autoimmune diabetes in mice.

AIM: To investigate the effect of plasmid coding interleukin-10 (IL-10) DNA on the development of autoimmune diabetes induced by multiple low doses of streptozotocin (STZ) in mice. METHODS: Injection of STZ (40 mg/kg, i.p.) was given daily for five consecutive days. pcDNA3-IL-10 plasmid (IL-10-treated group) or pcDNA3-null plasmid (pcDNA3-null-treated group) (100 microg DNA once a day) were injected into skeletal muscles of mice on d 1 and d 14. Blood glucose concentration was measured. After mice were killed on d 28, serum IFN-gamma level was measured by ELISA, and pancreatic IL-1beta and TNF-alpha mRNA expression was detected by semi-quantitative reverse-transcription PCR (RT-PCR). The number of CD4+ and CD8+ lymphocytes from spleen was detected using FACS. In addition, pancreatic histology was measured for determination of insulitis grades. RESULTS: Treatment with pcDNA3-IL-10 resulted in the retention and expression of the vector in skeletal muscle, associated with a considerable elevation in the plasma level of IL-10, which was not observed in pcDNA3-null-treated mice. In IL-10-treated diabetic mice induced by STZ, delay-type hypersensitivity responses were suppressed and the glucose level was greatly lower on d 14, 21, and 28 than pcDNA3-null-treated group (P<0.05 or P<0.01). On d 21 and 28 the incidence of diabetes was 33.3% and 40.0%, respectively, which was markedly lower than that of pcDNA3-null-treated group (P<0.05). In IL-10-treated mice pancreatic IL-1beta and TNF-alpha mRNA expression was depressed, and serum IFN-gamma concentration and the number of spleen CD4+ or CD8+ lymphocytes were decreased on d 28. The insulitis grades of IL-10-treated mice were lower than that of pcDNA3-null-treated group (P<0.01). CONCLUSION: Systemic administration of IL-10 plasmid DNA can alleviate insulitis of experimental autoimmune diabetes in mice and reduce incidence of diabetes.

Animals↗