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Biomedical subjects

Y C Kong

Publications and source records attributed to Y C Kong.

At least 19 recordsLinked to original sources
PubMed2001

Participation of Vbeta13(+) and Vbeta1(+) T cells in transfer thyroiditis after activation of mouse thyroglobulin-primed T cells by superantigen staphylococcal enterotoxin A.

Murine experimental autoimmune thyroiditis (EAT) is a T-cell-mediated disease, but the T cell receptor (TCR) Vbeta gene usage in pathogenesis has not been well delineated. One approach is to utilize bacterial superantigens, such as staphylococcal enterotoxin (SE) A and B, to stimulate known sets of TCR Vbeta families in mouse thyroglobulin (mTg)-primed cells for thyroiditis transfer. Our previous use of SEB to activate mTg-primed cells led to no thyroiditis transfer, despite a major increase in Vbeta8(+) T cells. Unlike SEB, SEA activation did transfer thyroiditis. To determine which thyroiditogenic Vbeta(+) T cells were involved, SEA-activated T cells have now been analyzed. After repeated SEA activation in vitro, both mTg-reactive and thyroiditogenic cells persisted. FACS analysis indicated that most Vbeta13(+) cells were "large" cells (IL-2R(+)) and expressed the activation marker, transferrin receptor (CD71). RT-PCR analysis also showed the presence of both Vbeta13(+) and SEA-reactive Vbeta1(+) cells. Since our previous analyses by RT-PCR of the thyroid infiltrate after either induction or adoptive transfer have implicated both Vbeta13(+) and Vbeta1(+) cells, their activation by SEA to transfer thyroiditis further supports their role.

Animals↗
PubMed2001

Characterization of a novel H2A(-)E+ transgenic model susceptible to heterologous but not self thyroglobulin in autoimmune thyroiditis: thyroiditis transfer with Vbeta8+ T cells.

Recently we reported on a novel H2E transgenic, IA-negative model of experimental autoimmune thyroiditis (EAT) that excludes reactivity to self in its susceptibility pattern to heterologous thyroglobulin (Tg). In conventional, susceptible mouse strains, EAT is inducible with both homologous and heterologous Tg; e.g., human (h)Tg shares conserved thyroiditogenic epitopes with mouse (m)Tg. However, when an H2Ea(k) transgene is introduced into class II-negative B10.Ab(0) mice, which express neither surface IA (mutant Abeta-chain) nor surface IE (nonfunctional Ea gene), the resultant H2E(b) molecules are permissive for EAT induction by hTg, but not self mTg. Also, the hTg-primed cells do not cross-react with mTg. To explore this unique capacity of E+B10.Ab(0) mice to distinguish self from nonself Tg, we have developed T cell lines to examine the T cell receptor repertoire and observed a consistent Vbeta8+ component after repeated hTg stimulation. Enrichment and activation of Vbeta8+ T cells by either superantigen staphylococcal entertoxin B or anti-Vbeta8 in vitro enabled thyroiditis transfer to untreated A-E+ recipients, similar to hTg activation. Vbeta8+ T cells isolated by FACS from hTg-immunized mice also proliferated to hTg in vitro. These studies support the contribution of Vbeta8 genes to the pathogenicity of hTg in this H2A-E+ transgenic model.

Animals↗
PubMed2001

IL-12 prevents tolerance induction with mouse thyroglobulin by priming pathogenic T cells in experimental autoimmune thyroiditis: role of IFN-gamma and the costimulatory molecules CD40l and CD28.

Deaggregated mouse thyroglobulin (dMTg) induces tolerance to experimental autoimmune thyroiditis (EAT), a Th1-cell-mediated disease. To test whether IL-12, a potent activator of Th1 cells, can overcome tolerance induction, different doses of IL-12 were given to CBA/J mice during the critical interval of 2--3 days after dMTg administration. After challenge with MTg/LPS, dMTg/IL-12-pretreated mice showed more extensive thyroiditis than immunized controls, but comparable levels of anti-MTg and T cell proliferation. Without challenge, few MTg antibodies were produced. In contrast, pretreatment with dMTg/poly A:U or dMTg/IL-1, two other T cell activators which also interfere with tolerance induction, induced antibodies before challenge, but not more severe thyroiditis. Mice pretreated with IL-12 without dMTg developed thyroiditis comparable to immunized controls, but less severe thyroiditis than dMTg/IL-12-pretreated mice. Clearly, IL-12 not only blocked tolerance induction, but also primed antigen-specific T cells during the tolerogenic period of dMTg pretreatment, resulting in stronger thyroiditis than immunization only. Neither treatment with anti-IFN-gamma nor the use of IFN-gamma knockout mice altered the capacity of IL-12 to prevent tolerance induction. However, both anti-CD28 and anti-CD40L antibodies diminished the priming effect by dMTg/IL-12. The mechanisms of IL-12 action include priming of MTg-specific T cells and the involvement of T cell costimulatory molecules.

Animals↗
PubMed2001

Flexibility of TCR repertoire and permissiveness of HLA-DR3 molecules in experimental autoimmune thyroiditis in nonobese diabetic mice.

Experimental autoimmune thyroiditis (EAT) is inducible in genetically susceptible mice by immunization with mouse thyroglobulin (mTg). With susceptibility linked to MHC class II, EAT is useful in studying human leukocyte antigen (HLA) associations with Hashimoto's thyroiditis. In non-obese diabetic (NOD) mice, approximately 10% thyroiditis incidence occurs with aging. This potential was exploited to examine the T cell repertoire and HLA association in EAT. Similar to B10.K-Vbeta(c)mice with TCRBV genes reduced by approximately 70%, mTg-immunized NOD-Vbeta(c)mice developed thyroiditis comparable to controls, indicating plasticity of the TCR repertoire for pathogenic epitopes. HLA association was evaluated by introducing HLA-DRA/DRB1*0301 (DR3) transgene into class II-negative NOD mice (Ab(0)/NOD). Previously, this HLA-DR3 transgene rendered EAT-resistant B10.M and Ab(0)mice susceptible to both mTg- and hTg-induced EAT. These results are now confirmed. mTg-induced thyroiditis in DR3+ Ab(0)/NOD mice was comparable to that in NOD and DR3- NOD mice, and the proliferative response was stronger. By comparison, NOD mice were only moderately susceptible to hTg-induced EAT. However, thyroiditis was more severe in DR3+ Ab(0)/NOD than in DR3- NOD mice, with no difference in proliferative response to hTg harbouring heterologous epitopes. The confirmed permissiveness of HLA-DR3 molecules on an NOD background for EAT induction by both mTg and hTg supports the importance of this class II gene implicated in some patient studies.

Animals↗
PubMed2001

Effects of schisandrin B pretreatment on tumor necrosis factor-alpha induced apoptosis and Hsp70 expression in mouse liver.

Tumor necrosis factor-alpha (TNFalpha) could cause apoptosis in hepatic tissue of D-galactosamine sensitized mice, as evidenced by the increase in the extent of DNA fragmentation. The hepatic apoptosis induced by TNFalpha was associated with hepatocellular damage as assessed by plasma alanine aminotransferase activity. Schisandrin B (Sch B) pretreatment at daily doses ranging from 0.5 to 2 mmol/kg for 3 days caused a dose-dependent protection against TNFalpha-induced apoptosis in mice. The hepatoprotection was accompanied by a parallel reduction in the extent of hepatocellular damage. The same Sch B pretreatment regimens increased hepatic Hsp70 level in a dose-dependent manner. The relevance of Sch B-induced increase in Hsp70 expression to the prevention of TNFalpha-triggered hepatic apoptosis remains to be elucidated.

Animals↗
PubMed2001

[The effect of kudingcha (Ilex latifolia Thunb.) on the contraction of isolated guinea-pig tracheal smooth muscle in vitro].

OBJECTIVE: To study the effects of Kudingcha (Ilex latifolia Thunb., IL) on the isolated guinea pig tracheal smooth muscle in vitro. METHOD: By obtaining CaCl2 and Histamine accumulative dose-response curves, to observe the influences of IL on the contraction of tracheal strips induced by calcium and some asthmogenic mediators. RESULT: CaCl2 and histamine caused significant contraction of tracheal smooth muscle and pD2 was 3.55 and 5.34 respectively. After incubated with IL, the dose-response curves of CaCl2 and histamine were significantly shifted to the right, and the maximal contractile force was reduced. IL could also inhibit isolated tracheal strip contraction induced by acetylcholine 3 x 10(-6) mol.L-1 and histamine 3 x 10(-6) mol.L-1, and IC50 was 0.16 mg.ml-1 and 0.21 mg.ml-1. CONCLUSION: Kudingcha has significant dilated effects on tracheal smooth muscle.

Animals↗
PubMed2000

Pathogenic thyroglobulin peptides as model antigens: insights on the induction and maintenance of autoimmune thyroiditis.

In recent years, the discovery of pathogenic thyroglobulin (Tg) peptides has given a new impetus to study, at the basic level, mechanisms of induction and immunoregulation of autoimmune thyroiditis. The genetic control of the immune response against defined Tg epitopes and the diversity of the T-cell receptor repertoire recruited for their recognition were among the first issues examined. Some of these epitopes contained hormonogenic sites, i.e. thyroxine residues, and thus offered an excellent opportunity to study how post-translational modifications such as iodination, can influence induction of thyroiditogenic cells. The delineation of pathogenic Tg determinants also enabled the search for "molecular mimics" i.e. peptides of microbial origin that may be involved in the pathogenesis of the disease. In addition, factors promoting the generation of pathogenic epitopes during Tg processing in antigen presenting cells could now be systematically investigated. This review summarizes recent findings in these areas.

Amino Acid Sequence↗
PubMed2000

New revelations in susceptibility to autoimmune thyroiditis by the use of H2 and HLA class II transgenic models.

H2 and HLA transgenes were utilized to clarify the role of class II genes in susceptibility to experimental autoimmune thyroiditis (EAT), a model for Hashimoto's thyroiditis (HT). Susceptibility was transferred by H2 class II transgenes to a resistant haplotype and by HLA-DRA/DRB1*0301 (DR3) transgene into class II-negative Ab0 mice. Mice with a HLA-DRB1*1502 (DR2) transgene remain resistant to mouse thyroglobulin (mTg)-induced EAT, illustrating the role of HLA-DRB1 polymorphism. A role for HLA-DQ polymorphism was shown with hTg-induced EAT in HLA-DQ*0301/DQB1*0302 (DQ8), but not HLA-DQ*0103/DQB1*0601 (DQ6), transgenic mice. Yet, both DQ8+ and DQ6+ mice were unresponsive to mTg. Single transgenes obviate the problems from DR/DQ linkage disequilibrium and may distinguish the degree of susceptibility and the response to shared or specific epitopes. The introduction of conserved Eak transgene into Ab0 mice reveals a new role for H2E molecules in EAT. Without H2A molecules, EalphaEbetab molecules and T cells respond to hTg or pTg with severe thyroiditis, but not to mTg, thus distinguishing self from nonself. However, IAb genes in resistant mice ameliorate Eak transgene-mediated thyroiditis, similar to the effect of Eak transgene on IAs-mediated EAT. Studies in HLA DQ/DR double transgenic mice simulating human haplotypes could reveal HLA class II gene interactions in HT.

Animals↗
PubMed1998

Induction of estradiol-2-hydroxylase and ethoxyresorufin-O-deethylase by 3-substituted indole compounds.

Estrogen can be hydroxylated at both 2- and 16alpha-positions. These two reactions are mutually exclusive. The 2-hydroxylated estrogen is relatively inactive compared with the 16alpha-derivative; hence, one approach in anti-estrogenic therapy is to look for drugs that can induce the 2-hydroxylation pathway. In the present study, using Balb/c and C57B/6 mice as the animal models, the induction effect of several isoprenyl compounds on estradiol-2-hydroxylase and ethoxyresorufin-O-deethylase activities was studied. The compounds examined included 2'- and 3'-methylbutadienyl-indoles and their respective acid condensation products, isopropyl indolocarbazole and yuehchukene; positional isomers of indole carbinols and carboxyaldehydes, as well as 3-methylcholanthrene, the prototype inducer of cytochrome P450 1A1. Our results demonstrated that while all of them were capable of inducing cytochrome P450 1A1-mediated ethoxyresorufin-O-deethylase activity, only the 3' isomers could induce estradiol-2-hydroxylase activity. The induction of these two activities did not show any direct correlation, suggesting that cytochrome P450 1A1 was not the same enzyme catalyzing both ethoxyresorufin-O-deethylation and estradiol-2-hydroxylation. Nevertheless, both inductions were mediated by the aryl hydrocarbon receptor. Among the compounds tested, yuehchukene showed competitive binding to estrogen receptor. This, together with the induction of estradiol-2-hydroxylase activity, may account for the anti-estrogenic effect of yuehchukene.

Alkaloids↗
PubMed1998

Noninvolvement of IL-4 and IL-10 in tolerance induction to experimental autoimmune thyroiditis.

The mechanisms of tolerance induced with deaggregated mouse thyroglobulin (dMTg) in experimental autoimmune thyroiditis (EAT) is not yet well defined. As shown previously, the induction and maintenance of tolerance require CD4+ T cells exerting active regulatory function to prevent EAT induction. To examine whether Th2 cells are responsible for resistance we injected anti-IL-4 and anti-IL-10, separately or together, into CBA (H2k) mice at the time of MTg pretreatment to study the role of IL-4 and IL-10 in tolerance induction. Our results show that tolerance can be well established without involving IL-4 or IL-10. To determine whether IL-4 was involved in tolerance induction in another EAT-susceptible strain, IL-4 knockout mice on B10.Q background were similarly pretreated with dMTg and immunized. These IL-4 knockout mice exhibited very good tolerance. The lack of response to EAT induction was not due to IL-4 deficiency, since immunized IL-4 knock-out control mice developed severe EAT. Moreover, resistance was strong in IL-4 knock-out mice also given anti-IL-10. The data in both susceptible strains show that IL-4 and IL-10 play a small role in induced resistance to EAT.

Animals↗
PubMed1998

Thyroglobulin peptides of specific primary hormonogenic sites can generate cytotoxic T cells and serve as target autoantigens in experimental autoimmune thyroiditis.

Previously we demonstrated that thyroxine (T4)-containing, 12-mer peptides from positions 5 (1-12) and 2553 (2549-2560), as well as thyronine (T0)-substituted 2553 peptide, derived from human (H) thyroglobulin (Tg) are capable of activating T cells that infiltrate the thyroid (thyroiditogenic). In contrast, peptides T4(2567) and T0(2567) (2559-2570) are not. To determine if these thyroiditogenic peptides, T4(5), T4(2553), and T0(2553), activated cytotoxic T cells (Tc) and served as target autoantigens when loaded onto indicator cells (BW5147 lymphoma, H2k), lymph node cells from CBA mice immunized with mouse (M) Tg were cultured in vitro with MTg, HTg, or Tg peptide. After MTg or HTg activation, Tc were detected for both MTg- and HTg-loaded target cells in an 18-h, 51Cr-release assay at an effector:target cell ratio of 50:1. These Tc also killed target cells labeled with T4(5), T4(2553), or T0(2553), but not the control peptide T4(2567). When MTg-primed lymphocytes were cultured with T4(5), T4(2553), or T0(2553), specific Tc were also generated against target cells labeled with the respective peptide. The data suggest that one of the thyroiditogenic properties of these peptides previously shown by adoptive transfer of thyroiditis is related to the generation of Tc. In addition, these conserved autoepitopes of Tg also serve as target antigens for Tc.

Animals↗
PubMed1998

Flexibility of the thyroiditogenic T cell repertoire for murine autoimmune thyroiditis in CD8-deficient (beta2m -/-) and T cell receptor Vbeta(c) congenic mice.

In murine experimental autoimmune thyroiditis (EAT), previous studies have revealed a highly adaptable thyroiditogenic T cell repertoire which involves both CD4+ and CD8+ T cells in the susceptible H2k strain. To further test this flexibility, congenic B10.K mice lacking CD8+ T cells (B2m -/-) or harboring 70% T cell receptor (TCR) Vbeta gene deletions (Vbeta(c)) were immunized with mouse thyroglobulin (MTg) and evaluated for EAT 28 days later. All B2m -/- mice developed moderate antibodies to MTg, and thyroidal inflammation was comparable to B10.K mice, averaging 35-40%. Spleen cells (SC) from MTg-immunized mice were then injected into syngeneic recipients after stimulation in vitro with MTg or with conserved, thyroxine (T4)- or thyronine (T0)- containing 12mer peptides, hT4(5), hT0(2553), or hT4(2553), derived from the primary hormonogenic sites at position 5 or 2553 of human Tg. As previously shown in another H2k strain (CBA/J), all three peptides activated MTg-primed SC to transfer EAT in B10.K mice. hT4(5) and hT4(2553) were further tested in B10.K-Vbeta(c) and beta2m- B10.K mice. Both peptides expanded thyroiditogenic T cells in either strain, resulting in severe thyroiditis in syngeneic recipients. That EAT can develop in the absence of CD8+ T cells or in the presence of a severely restricted TCR repertoire underscores the remarkable flexibility of the thyroiditogenic T cell profile in the susceptible k haplotype.

Adoptive Transfer↗
PubMed1996

HLA-DRB1 polymorphism determines susceptibility to autoimmune thyroiditis in transgenic mice: definitive association with HLA-DRB1*0301 (DR3) gene.

Familial clustering of autoimmune thyroid diseases has led to studies of their association with human major histocompatibility complex (MHC) class II genes. One such gene implicated in Hashimoto's thyroiditis (HT) is HLA-DR3, but the association is weak and is contradicted by other reports. On the other hand, murine experimental autoimmune thyroiditis (EAT), a model for HT, presents a clear linkage with MHC class II. Moreover, it is inducible with thyroglobulin (Tg), the common autoantigen in either species. Immunization of HLA-DRB1* 0301 (DR3) transgenic mice with mouse or human Tg resulted in severe thyroiditis. In contrast, transgenic mice expressing the HLA-DRB1*1502 (DR2) gene were resistant to EAT. Our studies show that HLA-DRB1 polymorphism determines susceptibility to autoimmune thyroiditis and implicate Tg as an important autoantigen.

Animals↗
PubMed1996

Schisandrin B protects against carbon tetrachloride toxicity by enhancing the mitochondrial glutathione redox status in mouse liver.

Previous studies in our laboratory have demonstrated the effect of Schisandrin B (Sch B),an active ingredient of the fruit of Schisandra chinensis, on enhancing the hepatic glutathione antioxidant system in mice, as evidenced by the hepatoprotection against carbon tetrachloride (CCl4) toxicity. In the present study, the mechanism involved in the hepatoprotection afforded by Sch B treatment was investigated. Treating female Balb/c mice with 1, 3-bis(2-chloroethyl)-1-nitrosourea, an inhibitor of glutathione reductase (GRD), at a dose of 2 mmol/kg (i.p.) did not abrogate the hepatoprotective action of Sch B in CCl4-treated mice. The result indicates that the increased activity of hepatic GRD is not ascribable to the hepatoprotective action of Sch B. In control mice, the same Sch B treatment regimen caused an enhancement in hepatic mitochondrial glutathione redox status, as indicated by the significant increase and decrease in reduced and oxidized glutathione levels, respectively. While the CCl4 intoxication greatly impaired mitochondrial glutathione redox status, the beneficial effect of Sch B treatment became more evident after CCl4 challenge. Our results strongly suggest that the mechanism of hepatoprotection afforded by Sch B treatment may involve the enhancement of mitochondrial glutathione redox status.

Alanine Transaminase↗
PubMed1996

Elucidation of Islamic drugs in Hui Hui Yao Fang: a linguistic and pharmaceutical approach.

Hui Hui Yao Fang, an Islamic formulary, was probably the official formulary of the Mongolian administration during the Yuan dynasty (13th-14th century) in China. In the three chapters of prescriptions that remain extant today, there are 517 Islamic drugs carrying Arabic or Persian names, each with its Chinese transliteration. Chapter 12 deals with the 'wind' diseases, containing 199 Islamic drugs. In this research, 129 items were identified, and each of which was assigned to a definite taxon; these are the most frequently cited drugs in the formulary. Identifications were corroborated by botanical, pharmacological and phonetic considerations. This exercise demonstrates the inherent affinity between Islamic and Chinese medicines. The reciprocal influence between them greatly enriched the content of these two important bodies of drug science, thus, setting a pattern for the synthesis of drug knowledge and the regulation of therapeutic substances. Recognition of different bodies of ethnomedicine is necessary in view of the fact that there is an increasing mobility of people today, who tend to bring with them their drug knowledge.

Formularies as Topic↗
PubMed1995

Primary hormonogenic sites as conserved autoepitopes on thyroglobulin in murine autoimmune thyroiditis. Secondary role of iodination.

We hypothesized earlier that conserved T cell epitopes and those unique to mouse thyroglobulin (MTg) contributed to its total thyroiditogenicity in murine autoimmune thyroiditis. Recent studies of synthetic peptides from human Tg (HTg) revealed no immunodominant epitopes. The role of iodine residues, considered by some to render Tg immunogenic, became unclear, since only one 12-mer peptide contained thyroxine (T4) positioned at hormonogenic site 2553. It primed T cells for thyroiditis transfer, but noniodinated peptide containing thyronine (T0) was not compared. To determine 1) whether other primary hormonogenic sites were likewise immunogenic and 2) whether iodination was requisite for this and other sites to be an autoepitope, we derivatized three pairs of 12-mer peptides, 1-12, 2549-2560, 2559-2570, containing T0 or T4 at positions 5, 2553, or 2567, respectively. The six peptides were used to stimulate MTg-primed cells in vitro and to immunize mice. None directly induced thyroiditis; peptide Abs were the lowest in mice given hT0(2567) or hT4(2567). Of the three T4-containing peptides, hT4(5) and hT4(2553), but not hT4(2567), stimulated MTg-primed or HTg-primed T cells in vitro, with hT4(2553) being the stronger. Comparing hT0(2553) with hT4(2553), both activated MTg-primed, or peptide-primed, T cells to transfer thyroiditis. The marked immunogenicity of noniodinated hT0(2553) and the poor antigenicity of hT4(5) and hT4(2567) demonstrate that immunogenicity of a conserved hormonogenic site is dependent more on its amino acid sequence than on T4 substitution. Iodination may enhance antigenicity and/or binding affinity, but it is not required for a Tg hormonogenic site to be an autoepitope.

Amino Acid Sequence↗
PubMed1995

Effect of a lignan-enriched fructus schisandrae extract on hepatic glutathione status in rats: protection against carbon tetrachloride toxicity.

The effect of a lignan-enriched extract of the fruits of Schisandra chinensis (FS) on hepatic glutathione (GSH) status was examined in both control and carbon tetrachloride (CCl4)-treated rats. FS treatment caused a dose-dependent enhancement in hepatic GSH status, as evidenced by significant increases in hepatic GSH level and activities of hepatic glucose-6-phosphate and glutathione reductase (GRD), as well as a decreased susceptibility of hepatic tissue homogenates to in vitro peroxide-induced GSH depletion. The beneficial effect of FS treatment on hepatic GSH status became more evident after CCl4 challenge. Pretreating rats with FS extract at increasing daily doses ranged from 0.2 to 3.2 g/kg for 3 days caused a dose-dependent protection against the CCl4-induced impairment in hepatic GSH status. The enhancement in hepatic GSH status was associated with corresponding decreases in tissue malondialdehyde levels and plasma alanine aminotransferases activities, indicating a significant reduction in the extent of oxidative hepatocellular damage. Our results indicate that the molecular mechanism of hepatoprotection afforded by FS pretreatment may involve the facilitation of GSH regeneration via the GRD-catalyzed and NADPH-mediated reaction.

Animals↗