Biomedical subjects

W S Koh

Publications and source records attributed to W S Koh.

26 records · Page 2Linked to original sources

PubMed1995

2-Acetylaminofluorene inhibits the activation of immune responses by blocking cell cycle progression at G1 phase.

2-Acetylaminofluorene (AAF) inhibited in a dose dependent manner mouse spleen cell blastogenesis in response to phorbol 12-myristate 13-acetate (PMA)/Ionomycin (Io) activation, the T-cell lectin, concanavalin A (Con A), and following stimulation by alloantigens as measured by the mixed lymphocyte response (MLR). AAF also markedly suppressed the T-cell dependent antibody forming cell (AFC) response to sRBC. AAF was most inhibitory on both the sRBC IgM AFC response and Con A stimulated proliferation when added during the first 24 h following initiation of culture. Direct addition of high concentrations of AAF (100 microM) to spleen cell cultures at 48 h following Con A stimulation produced a very modest inhibition (< 20%) of T-cell proliferation as compared to 90% when added at the time cultures were initiated. Similarly, AAF (75 and 100 microM) produced a greater than 80% inhibition of the in vitro AFC response when spleen cells were sensitized with antigen in presence of AAF. In contrast, no inhibition of the IgM AFC response was produced when AAF (75 microM) was added to spleen cell cultures 48 or 72 h after antigen sensitization. Con A-triggered cell-cycle progression was attenuated at the G1 stage by the addition of AAF (50 and 100 microM) with no inhibition of S to G2/M phase transition. These results suggest that the mechanism of AAF-mediated immune suppression is through a blockade of cell cycle progression from G1 to S phase.

2-Acetylaminofluorene↗

PubMed1994

Suppression of the humoral immune response by cannabinoids is partially mediated through inhibition of adenylate cyclase by a pertussis toxin-sensitive G-protein coupled mechanism.

Cannabinoid compounds, including the major psychoactive component of marihuana, delta 9-tetrahydrocannabinol (delta 9-THC), have been widely established as being inhibitory on a broad array of humoral and cell-mediated immune responses. The presence of cannabinoid receptors has been identified recently on mouse spleen cells, which possess structural and functional characteristics similar to those of the G-protein coupled cannabinoid receptor originally identified in rat brain. These findings, together with those demonstrating that delta 9-THC inhibits adenylate cyclase in splenocytes, strongly suggest that certain aspects of immune inhibition by cannabinoids may be mediated through a cannabinoid receptor-associated mechanism. The objective of the present studies was to determine whether inhibition of adenylate cyclase is relevant to mouse spleen cell immune function and, if so, whether this inhibition is mediated through a Gi-protein coupled mechanism as previously described in neuronal tissue. Spleen cell activation by the phorbol ester phorbol-12-myristate-13-acetate (PMA), plus the calcium ionophore ionomycin, produced a rapid but transient increase in cytosolic cAMP, which was inhibited completely by immunosuppressive concentrations of delta 9-THC (22 microM) and the synthetic bicyclic cannabinoid CP-55940 (5.2 microM), which produced no effect on cell viability. Inhibition by cannabinoids of lymphocyte proliferative responses to PMA plus ionomycin and sheep erythrocyte (sRBC) IgM antibody-forming cell (AFC) response, was abrogated completely by low concentrations of dibutyryl-cAMP (10-100 microM). Inhibition of the sRBC AFC response by both delta 9-THC (22 microM) and CP-55940 (5.2 microM) was also abrogated by preincubation of splenocytes for 24 hr with pertussis toxin (0.1-100 ng/mL). Pertussis toxin pretreatment of spleen cells was also found to directly abrogate cannabinoid inhibition of adenylate cyclase, as measured by forskolin-stimulated accumulation of intracellular cAMP. These results indicate that inhibition of the sRBC AFC response by cannabinoids is mediated, at least in part, by inhibition of adenylate cyclase through a pertussis toxin-sensitive Gi-protein coupled cannabinoid receptor. Additionally, these studies further support the premise that cAMP is an important mediator of lymphocyte activation.

Adenylate Cyclase Toxin↗

PubMed1994

Relevance of skin phototyping to a Korean population.

We have determined skin phototype by a self-reporting questionnaire proposed by Fitzpatrick in 128 Korean medical students. We also measured the minimal erythema dose (MED), minimal melanogenic dose and investigated their relationship to phototype. A questionnaire of skin phototypes revealed that 13.3% of the students are skin phototypes I and II. Based on MEDs, we demonstrated that 14.8% of the students fall into the UV-sensitive group as defined by an MED of less than 40 mJ/cm2, which is the upper range of MED of phototypes I and II in a white population. The skin phototypes did not show a positive correlation to MEDs and only 2.3% of students classified as skin phototypes I and II showed an MED below 40 mJ/cm2. This study indicates that the skin phototyping method proposed by Fitzpatrick does not reliably predict UV-sensitive individuals within the Korean population.

Adult↗

PubMed1994

Suppressive effects of 2-acetylaminofluorene on concanavalin A-stimulated murine splenocyte proliferation in vitro: inhibition of interleukin-2 receptor expression.

Treatment of 2-acetylaminofluorene (AAF) to murine splenocyte culture produced a dose-related suppression on the lymphoproliferative response to concanavalin A (Con A). The amount of interleukin 2 (IL-2) activity in the culture supernatants was increased when AAF was treated for 48 hr. Since IL-2 activity did not increase if AAF was treated for the last 4 hr of a 48-hr culture period, the increase of IL-2 activity in culture supernatants did not appear to be due to the leakage of IL-2 from intracellular pool. Treatment of colchicine, an agent known to increase IL-2 activity in culture supernatants by inducing the cytoskeletal structure modification, increased IL-2 activity in splenocyte culture supernatants in 4 hr treatment. Meanwhile, the IL-2 receptor alpha (IL-2R alpha) positive cell population was decreased by the treatment of AAF. These results suggested that suppressive effects of AAF on the lymphoproliferative response to Con A in murine splenocyte culture may be associated with the inhibition of IL-2 receptor expression.

2-Acetylaminofluorene↗

PubMed1994

Suppression of TCDD-induced cytochrome P450 IA1 activity by staurosporine in mouse primary hepatocyte cultures and hepatoma cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induced cytochrome P450 IA1 activity in mouse primary hepatocyte cultures and mouse hepatoma Hepa-1 cells. Pretreatment with staurosporine, a protein kinase C inhibitor, inhibited TCDD-activated cytochrome P450 IA1 expression dose-dependently in both culture systems. Staurosporine also decreased P450IA1 protein synthesis which was detected using western immunoblot. Increased transcription of CYP1A1 gene by TCDD was also suppressed by staurosporine treatment. However, tyrphostin AG213, a specific tyrosine kinase inhibitor, had no effects on TCDD-induced cytochrome P450 expression. These results suggest that protein kinase C signal transduction may be involved in the cytochrome P450 induction mechanism by TCDD.

Alkaloids↗

PubMed1993

Hepatocyte growth factor enhances B-cell activity.

Hepatocyte growth factor (HGF), is one of the growth factors induced and secreted into the serum of partially hepatectomized or hepatotoxin-treated mice that mediates regeneration of hepatic tissue. Results are presented here demonstrating that in addition to hepatotrophic effects, HGF also possesses immunologic activity. In particular, addition of HGF to B6C3F1 mouse spleen cell cultures enhanced humoral immune responses by augmenting the ability of B-cells to secrete immunoglobulin.

Animals↗

PubMedDate not supplied

Delta 9-tetrahydrocannabinol selectively inhibits T-cell dependent humoral immune responses through direct inhibition of accessory T-cell function.

The major psychoactive and immunosuppressive component of marihuana, delta 9-tetrahydrocannabinol (delta 9-THC), was investigated for its effects on primary humoral immune responses in the B6C3F1 mouse strain. Oral administration of 50-200 mg/kg delta 9-THC produced a selective and dose related inhibition of primary humoral immune responses to the T-cell dependent antigen, sRBC, as measured by the antibody forming cell (AFC) response with no inhibitory effect on humoral responses to the T-cell independent antigen, DNP-Ficoll. A similar profile of immune inhibition was observed following in vitro direct addition of delta 9-THC to naive spleen cell cultures sensitized with defined antigens. delta 9-THC produced a marked and dose related inhibition of the in vitro sRBC AFC response while having no inhibitory effects on T-cell independent responses to either DNP-Ficoll or the polyclonal B-cell activator, lipopolysaccharide. This selective inhibition of the sRBC response was not due to a shift in the peak day of response or a direct cytotoxic effect on spleen cells. In vivo kinetic studies demonstrated that inhibition by delta 9-THC of the sRBC response was most pronounced when drug administration occurred at times surrounding antigen sensitization. To further evaluate the direct effect of delta 9-THC on T-cell function, T-cell proliferative responses to stimulation by anti-CD3 monoclonal antibodies were measured. delta 9-THC was found to produce a marked and dose related inhibition of anti-CD3 mAb-induced T-cell proliferation which was cell density dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMedDate not supplied

Differential effects and transport kinetics of ascorbate derivatives in leukemic cell lines.

In order to investigate the differential effects of ascorbate derivatives on leukemic cell growth, we examined their stabilities and transmembrane transport efficiencies. The growth of HL-60 and U937 cells was dose-dependently inhibited by ascorbic acid and sodium ascorbate, but not by dehydroascorbic acid and magnesium ascorbyl 2-phosphate up to 200 microM. The growth-suppression by ascorbic acid was dependent on its redox state, showing a complete or partial reversion by ascorbate oxidase or FeCl3 addition, respectively. Three different patterns of intracellular ascorbic acid accumulation were observed by HPLC according to the species of ascorbate derivative applied for the incubation. Compared with the reduced form of ascorbic acid, the oxidized forms (dehydroascorbic acid, ascorbic acid plus ascorbate oxidase or FeCl3) were rapidly transported into cells and readily degraded, while magnesium ascorbyl 2-phosphate, a stable derivative of ascorbic acid, slowly elevated the intracellular level of ascorbic acid, reaching a plateau at 24 hours. We also measured the differential kinetics of ascorbic acid levels In culture supernatants following the addition of ascorbate derivatives. Ascorbic acid at 40, 10, or 1 microM was observed 3 hours following treatment with 100 microM of ascorbic acid, ascorbic acid plus FeCl3, or magnesium ascorbyl 2-phosphate, respectively. No ascorbic acid was found in the culture supernatant treated with dehydroascorbic acid. This order of ascorbic acid concentrations in culture supernatant reflects their growth-inhibitory effects. Thus the growth inhibitory effect of ascorbic acid appears to be dependent on its concentration in culture medium rather than its intracellular concentration. In conclusion, the results in this study indicate that the differential effects of ascorbate derivatives appear to be due to the actual concentration differences of the reduced form of ascorbic acid in culture medium following their addition, which is determined by their stability and efficiency of cellular uptake.

Ascorbate Oxidase↗