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At least 433 records · Page 24Linked to original sources
PubMed1987

Lectin binding pattern of Hodgkin disease-derived cell lines in comparison to other human cell lines.

The three Hodgkin disease-derived cell lines L 428, L 540, and L 591 were characterized in their carbohydrate epitope composition by a panel of lectins. Nine other human cell lines were tested in comparison to the Hodgkin (H) and Sternberg Reed (SR) cells: promyelocytic (HL 60), lymphoblastoid, myeloma, histiocytic lymphoma (U 937), and other non-Hodgkin lymphoma cell lines. Twenty-four different fluoresceinated lectins bound to the Hodgkin and other cell lines in different percentages of positive cells and with varying intensities. Lotus lectin and a monoclonal anti-Lewis blood group X antibody showed very similar binding patterns (L 428, L 540, HL 60, U 937). Soybean agglutinin stained only L 428 and L 540, although nearly all were positive after neuraminidase treatment. Cell lysis of the three H cell lines resulted in a very similar electrophoretic mobility pattern of proteins. In addition, staining of transblotted glycoproteins with biotinylated concanavalin A by avidin peroxidase reaction revealed corresponding bands. Differences were seen with Lotus staining. In summary, the origin of H cells is still unknown, but there is obviously some relationship in the glycoconjugate profile to the myelohistiocytic lineage.

Cell Line↗
PubMed1989

Morphological characteristics and ganglioside composition of substratum adhesion sites in a hepatoma cell line (CMH5123 cells) during different phases of growth.

This study compares the ganglioside composition of tissue culture substrate-attached material (SAM) with that of cell bodies in a line of transformed hepatocytes derived from the minimal deviation Morris hepatoma 5123 c (CMH5123 cells). We examined both confluent cultures (late-phase cultures) and cells which were allowed to attach for only 3 h (early-phase cultures). We also determined to what extent ganglioside compositions of SAM and cell bodies from early- and late-phase cultures of CMH5123 cells are affected by the block of complex ganglioside biosynthesis induced by treatment with chelating agents (EGTA + EDTA). The morphological characteristics of SAM were monitored by scanning electron microscopy during the different steps of this study. In early-phase cultures, SAM was composed of fragments of filopodia and small vesicles probably representing newly formed substratum adhesion sites. In contrast, SAM of late-phase cultures was made up of large pools of membranous material resulting from the breakage of thick retraction fibers connecting the cell body with broad, mature adhesion sites. SAM of early-phase cultures yielded ganglioside profiles with a higher content of GM1 and GD1 a than those of cell bodies, while in late-phase cultures there was no difference between SAM and cell body gangliosides. When cells were grown in the presence of chelating agents, SAM of early-phase cultures was composed of vesicles and filopodial fragments similar to those found in early-phase cultures grown in regular media; these morphological features also appeared in SAM of confluent cultures (in contrast to the membranous material characteristic of late-phase cultures grown in regular media). In early-phase cultures grown in the presence of chelating agents, gangliosides of SAM were enriched in complex homologs relative to their content in cell bodies. These ganglioside characteristics were also found in SAM of confluent cultures grown in the presence of chelating agents, reflecting the presence of newly formed adhesion sites. On the basis of these results, we may conclude that the molecular assembly of newly formed adhesion sites implies the preferential distribution of several surface components involved in cell adhesion, including complex gangliosides.

Animals↗
PubMed1994

Functional insulin and insulin-like growth factor-1 receptors are preferentially expressed in multiple myeloma cell lines as compared to B-lymphoblastoid cell lines.

While IGF-1 plays a role in early B-cell development, little is known of insulin and insulin-like growth factor-1 (IGF-1) action in post-marrow B-cells. Recently, our laboratory demonstrated that mouse and human multiple myeloma (MM) cell lines possess functional insulin receptors (IRs) and IGF-1 receptors (IGF-1Rs). In this study, we show that responsiveness to insulin and IGF-1 is more developed in human MM cell lines than in human B-lymphoblastoid cell lines. Two human MM cell lines (U266 and RPMI 8226) were compared to three B-lymphoblastoid cell lines [Epstein-Barr virus immortalized B-cells (EBV), a Burkitt lymphoma cell line (Ramos), and a non-EBV lymphoblastoid cell line (HS Sultan)]. Surface IR and IGF-1R expression, measured by flow cytometry, demonstrated that the MM cell lines expressed more IRs and IGF-1Rs than did the EBV, Ramos, or HS Sultan cell lines. In vitro receptor kinase activity of affinity-purified receptors showed that the MM cells had more phosphorylated receptors than did the EBV, Ramos, or HS Sultan cells. Intracellular receptor signaling was also markedly different between the two cell groups. Whole cell phosphorylation studies showed that MM cells possessed not only hormone-dependent receptor autophosphorylation (M(r) 97,000) but also substrate phosphorylation (M(r) 185,000; 60,000). The lymphoblastoid cells, while demonstrating receptor autophosphorylation (IR autophosphorylation in the EBV cell line at 200 nM hormone was similar to MM receptor phosphorylation at 2 nM), lacked hormone-responsive substrates. The MM cell lines contained significantly more hormone-stimulated phosphatidylinositol 3-kinase (PI 3-kinase) activity than the B-lymphoblastoid cell lines. In the MM cells, PI 3-kinase was activated by at least 10-fold, but, in the B-lymphoblastoid cell lines, it was activated by no more than 2-fold. Hormone-responsive glucose metabolism was also greater in the MM cell lines. In the U266 cells, insulin increased lactate production 62 +/- 9 and 101 +/- 12% (mean +/- SE) at concentrations of 2 nM and 200 nM, respectively. IGF-1 produced 72 +/- 9 and 99 +/- 13% increases at similar concentrations. In the 8226 cells, insulin increased lactate production 4 +/- 4 and 36 +/- 15% at 2 and 200 nM, respectively. IGF-1 produced a 13 +/- 6 and 70 +/- 18% increase. In the EBV and Ramos cells, neither hormone increased lactate production by more than 10 +/- 3%.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Establishment of cell lines from somatic cell hybrids between human monocytes and mouse myeloma cells.

To study human monocyte functions, we attempted to immortalize human monocytes by producing somatic cell hybrids between such monocytes and the mouse myeloma cell line NSI. In this study we report the successful establishment of eight hybrid cell lines that have been grown in culture for more than a year, and some of them retained part of the human chromosome complement, as well as monocyte markers and activities. Karyotype analysis of these hybrid lines revealed that cells of seven out of eight of the lines contained one to 16 human chromosomes and in four of them, more than nine human chromosomes were observed. Several of the cell lines expressed monocytic markers and functions. Thus, in two of the hybrid lines nonspecific esterase could be demonstrated in 10 to 29% of the cells, and Fc receptors were demonstrated in three of the hybrid cell lines. Significant levels of human ferritin were detected in one of the lines, and two other cell lines secreted interleukin 1-like substance into the culture medium. These results encourage us to use human-mouse somatic cell hybridization as an approach for the establishment of human monocyte cell lines, which will preserve their functions and produce monocyte-derived factors.

Animals↗
PubMed1996

Use of Mono Mac 6 human monocytic cell line and J774 murine macrophage cell line in parallel antimycobacterial drug studies.

The Mono Mac 6 (MM6) human monocytic cell line was evaluated with the established J774 murine macrophage cell line to ascertain its effectiveness in determining the intracellular activities of antimycobacterial drugs. Cells were infected with Mycobacterium tuberculosis H37Ra and treated with drug concentrations corresponding to the MICs, as well as to threefold higher than and threefold less than the MICs. Changes in CFU were compared after 7 days to determine significant differences between treated and nontreated groups. The results suggest that MM6 will make a useful model for testing the intracellular activities of antituberculosis drugs.

Animals↗
PubMed2004

Transfection of the multiple endocrine neoplasia type 1 gene to a human endocrine pancreatic tumor cell line inhibits cell growth and affects expression of JunD, delta-like protein 1/preadipocyte factor-1, proliferating cell nuclear antigen, and QM/Jif-1.

In the absence of metastases or overgrowth to adjacent organs, the lack of reliable markers for malignancy is a well-recognized problem for clinicians managing patients with endocrine tumors. Apart from inactivation of the multiple endocrine neoplasia type 1 (MEN1) gene, the molecular mechanisms involved in tumorigenesis of the endocrine organs and MEN1-associated nonendocrine lesions are vastly unknown. To try to learn more about down-stream effects on MEN1 gene inactivation, we used the BON1 cells, showing low levels of endogenous menin, and transfected them with a MEN1 gene construct. On restoring the menin expression, we recorded inhibition of cell growth. We also performed macroarray and present data on differentially expressed genes in the transfected cells, after corroboration by Northern blots and quantitative PCR. JunD was up-regulated in menin-expressing clones, whereas delta-like protein 1/preadipocyte factor-1 (involved in differentiation and growth of the pancreatic endocrine cells), proliferating cell nuclear antigen, and QM/Jif-1 (a negative regulator of c-Jun) became down-regulated. These findings might contribute to the understanding of the tissue-specific features of MEN1. We also show that homozygous inactivation of the MEN1 gene statistically correlates to higher expression of delta-like protein 1/preadipocyte factor-1, proliferating cell nuclear antigen, and QM/Jif-1, as well as lower MEN1 expression, in a limited sample of malignant endocrine pancreatic tumors.

Animals↗
PubMed1998

Higher export rate of homocysteine in a human endothelial cell line than in other human cell lines.

Even mild hyperhomocysteinemia is associated with premature vascular disease. Despite the growing evidence that plasma homocysteine is a cardiovascular risk factor, the mechanism behind the vascular injuries is still unknown. Information about the metabolism of homocysteine is, therefore, essential for an understanding of its role in atherogenesis. In the present study we have, therefore, investigated the export mechanism of homocysteine. In HeLa cell lines the release of homocysteine was found to be a continuous process, which was increased in the presence of copper ions. High cell density led to a lowered release of homocysteine, probably due to a more extensive metabolism of the intracellular homocysteine. It was also found that HeLa cells were able to take up extracellularly released homocysteine and use it in the cellular metabolism. The ratio between intracellular homocysteine and the total amount of homocysteine is a measure of the ability of the cell to export the intracellularly produced homocysteine. The ratio also reflects the reuse of extracellular homocysteine. Under basal conditions, endothelial cells exported most of the intracellularly produced homocysteine and exhibited a very low concentration of homocysteine intracellularly, low reusage of exported homocysteine and consequently a low ratio in comparison with HeLa and hepatoma cell lines. After addition of homocysteine, all cell lines exhibited similar ratios. Thus, the intracellular homocysteine concentration in endothelial cells is more influenced by the extracellular concentration of homocysteine than is the intracellular concentration in HeLa and hepatoma cells. It may be speculated that this phenomenon could be associated with an increased sensitivity of endothelial cells to homocysteine and explain the association between hyperhomocysteinemia and vascular disease.

Biological Transport↗
PubMed1982

Variation in selectivity of tumor cell cytolysis by murine macrophages, macrophage-like cell lines and NK cells.

Several murine tumor-cell lines were tested by isotope release assays for their susceptibility to lysis by either activated peritoneal macrophages (apMPh), macrophage-like (MPh-like) cell lines, or natural killer (NK) cells. The qualitative selectivity of tumor-cell lysis by these different effector cells was quite disparate. The rank order of target cell susceptibility to lysis by apMPh in 24 h assay was L5178Y greater than P815 approximately equal to RL male greater than YAC-1 approximately equal to MBL-2. This was seen regardless of whether peritoneal MPh (pMPh) were activated by LPS or poly I:C. Two MPh-like cell lines, PU-5R and FC-1, had a pattern of cytotoxic activity against these target cells that closely paralleled that associated with apMPh, although levels of reactivity differed quantitatively among the effector cells. In contrast, the MPh-like cell line RAW-264 expressed a qualitatively different pattern of target-cell selectivity, preferentially lysing MBL-2, which was relatively refractory to lysis by other MPh-like cell lines or apMPh in the 24 h cytolytic assay. When spontaneous or interferon (IFN)-augmented NK activity was measured against the same panel of target cells, the pattern of selectivity was qualitatively different from that observed for apMPh. The consistent rank order of susceptibility to lysis by NK cells was YAC-1 greater than RL male 1 greater than P815 approximately equal to L5178Y approximately equal to MBL-2. The characteristic patterns of target-cell selectivity for apMPh or NK cells were the same for all of the strains of mice tested. From the different selectivity patterns of apMPh and NK cells, it is concluded that lysis of target cells is not based solely on inherent sensitivity to cytolysis. Instead, selectivity of lysis is probably due to variations in expression of target-cell structures recognized by each type of effector cell, and/or in susceptibility to the lytic mechanism(s) of the various effector populations.

Animals↗
PubMed1993

Effect of various chemosensitizers on chemoresistance to adriamycin in MIP-101 cell line, a colon carcinoma cell line: analysis of glutathione and related enzymes.

We evaluated the multidrug resistance modulating effect of verapamil, buthionine sulfoximine, trifluoperazine and tamoxifen in a human colorectal cell line resistant de novo to adriamycin. We studied the effect of these chemosensitizers on glutathione content, glutathione reductase, transferases, peroxidases, gamma-glutamyl transpeptidase and glucose-6-phosphate dehydrogenase activities. The ratio of the activities between resistant and sensitive cells treated by these compounds as compared with the ratio of the untreated cells decreases, thus contributing to the reversal of chemoresistance. This study implies a role of glutathione and related enzymes in chemoresistance to adriamycin, although this is certainly not the sole mechanism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Effects of a novel trinuclear platinum complex in cisplatin-sensitive and cisplatin-resistant human ovarian cancer cell lines: interference with cell cycle progression and induction of apoptosis.

We evaluated the effects of the trinuclear platinum complex, BBR 3464, in a human ovarian carcinoma cell line (OAW42) and in its cisplatin (CDDP)-resistant counterpart (OAW42MER). A 14-fold increased sensitivity to a 1-h BBR 3464 exposure was found in OAW42MER cells compared with their parental cell line. Flow cytometric experiments showed that BBR 3464 was able to induce a persistent block of OAW42 and OAW42MER cells in the G2M phase, whereas CDDP caused an initial accumulation of cells in the S phase followed by an increase in the G2M cell fraction in both cell lines. Exposure to equitoxic (IC(50)) drug concentrations induced programmed cell death in both cell lines. However, the percentage of cells with an apoptotic nuclear morphology was slightly higher after CDDP than BBR 3464 treatment in OAW42 cells, whereas the opposite pattern was observed in OAW42MER cells. Degradation of the nuclear lamin B was detected in OAW42 cells after exposure to each drug. Conversely, in OAW42MER cells lamin B cleavage was only appreciable after BBR 3464 exposure. In OAW42 cells, CDDP and BBR 3464 did not appreciably affect the mitochondrial membrane potential (Deltapsi(mt)), whereas in the OAW42MER cell line a marked Deltapsi(mt) reduction was observed after exposure to BBR 3464, but not to CDDP. The results of the study would suggest that the sensitivity to BBR 3464 observed in the CDDP-resistant OAW42MER cell line might be attributable to the ability of the trinuclear platinum complex to modify DNA in a way which is different from that of CDDP and, as a consequence, to induce different cellular responses to DNA damage such as the triggering of specific apoptotic pathways.

Antineoplastic Agents↗
PubMed1988

The HuT series of 'carcinogen-transformed' human fibroblast cell lines are derived from the human fibrosarcoma cell line 8387.

In 1977 Kakunaga reported the carcinogen-induced transformation of the diploid human fibroblast cell line KD into focus-forming, morphologically altered cells. Cell lines were developed from 15 individual foci. These exhibited an infinite lifespan in culture and all those that were tested (7/7) formed malignant tumors (sarcomas) in athymic mice. The existing cell lines, designated HuT-11 to HuT-14, have been studied intensively during the past decade as examples of human fibroblasts malignantly transformed by treatment with a chemical carcinogen, 4-nitroquinoline-1-oxide. Recently, in comparing the HuT-11, HuT-12 and HuT-14 cell lines with KD cells, McCormick and Maher (Mutat. Res., 199, 273-291, 1988) found evidence that the malignant cells could not have been derived from the latter. But, this did not rule out the possibility that as the target cells for his original study of carcinogen-induced transformation, Kakunaga had inadvertently used cells from some other, unidentified normal individual. Since the donor of such cells would not be known and the original cell line was not available, it would be impossible to determine the degree of identity between such a target cell line and the HuT cell lines. However, in the course of examining methods for such testing, we recently became aware that the isozyme pattern of these HuT cell lines was identical to that of the human fibrosarcoma-derived cell line 8387 established in 1966. We here report that the HuT cell lines and the 8387 cell line also exhibit an identical series of HLA determinants and identical restriction fragment length polymorphisms (RFLPs). Assuming that each of these three assays measures independently inherited characteristics, the chance that an unrelated donor of the fibroblasts that gave rise to the HuT cell lines happened to possess characteristics identical to those of the patient whose fibrosarcoma gave rise to the 8387 cell line is 1 x 10(-8). Therefore, we conclude that 8387 cells are the source of the malignant cells designated HuT from Kakunaga's original transformation experiment. Additional RFLP analysis, using a probe made from M13 bacteriophage DNA which detects a hyperpolymorphic 'minisatellite' pattern in human DNA, also showed that DNA from HuT-14 cells and from 8387 cells exhibit identical banding patterns, indicating that the cell lines were taken from the same individual. The latter banding patterns differed from that observed with DNA from KD cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Human PTH-(3-34) inhibited the effects of human parathyroid hormone-related protein on phosphate uptake in a cultured renal cell line (OK cells).

The action mechanism of hPTH and hPTHrP-(1-34) on phosphate uptake in opossum kidney (OK) cells was studied using [Nle8,18Tyr34]hPTH-(3-34)-NH2, a potent competivie inhibitor of adenylate cyclase-coupled PTH receptor. We examined the effects of hPTH-(1-34), hPTHrP-(1-34), and hPTH-(3-34) separately or in combination on the change in renal cyclic AMP production and phosphate uptake in OK cells. Both hPTH-(1-34) and hPTHrP-(1-34) stimulated intracellular cyclic AMP production to the same degree at concentrations between 10(-10) and 10(-7) M and inhibited phosphate uptake equipotently on a molar basis (27.5 +/- 2.0 and 33.2 +/- 1.2% inhibition at 10(-7) M, respectively). Both exogenous addition of (Bu)2cAMP and endogenous stimulation of cAMP by forskolin inhibited phosphate uptake in a dose-dependent manner. Cyclic AMP production induced by either hPTH-(1-34) or hPTHrP-(1-34) was inhibited by both [Nle8,18Tyr34]-hPTH-(3-34)-NH2 and [Tyr34]-hPTH-(7-34)-NH2. However, [Nle8,18Tyr34]hPTH-(3-34)-NH2 and [Tyr34]-hPTH-(7-34)-NH2 inhibited hPTH-induced cAMP production more strongly. The inhibitory action of phosphate uptake by hPTH-(1-34) and hPTHrP-(1-34) was prevented in the presence of a 100-fold greater concentration of [Nle8,18Tyr34]hPTH-(3-34)-NH2. The antagonistic action of [Nle8,18Tyr34]hPTH-(3-34)-NH2 on the inhibition of phosphate uptake induced by hPTH-(1-34) and hPTHrP-(1-34) became weaker with time (0-120 minutes), and [Nle8,18Tyr34]hPTH-(3-34)-NH2 did not antagonize the inhibition of phosphate uptake induced by hPTHrP-(1-34) at 120 minutes of incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Induction of human beta-defensin-2 mRNA expression by Helicobacter pylori in human gastric cell line MKN45 cells on cag pathogenicity island.

Helicobacter pylori is an etiological agent of gastritis, peptic ulcer, and gastric cancer. Human beta-defensin-2 (hBD-2) is an antimicrobial peptide which belongs to one of the most important host defense systems against bacterial infection in several epithelial tissues. We studied the effect of H. pylori on the expression of hBD-2 mRNA in MKN45 gastric mucosal cells. H. pylori, but not culture filtrate, increased the hBD-2 mRNA level in MKN45 cells; the inductive effect of H. pylori was not detected with Intestine 407 cells. Among H. pylori strains, strain OHPC0002, which lacks a cag Pathogenicity Island (PAI), did not induce hBD-2 mRNA in MKN45 cells. These results suggested that H. pylori cag PAI is critical for the induction of hBD-2 mRNA in MKN45 cells. Exposure of MKN45 cells to Salmonella typhimurium, S. enteritidis, S. typhi, and S. dublin, but not Escherichia coli ML35, also resulted in induction of hBD-2 mRNA.

Blood Bactericidal Activity↗
PubMed1998

The effects of nucleotides and potassium channel openers on the SUR2A/Kir6.2 complex K+ channel expressed in a mammalian cell line, HEK293T cells.

The effects of potassium channel opening drugs and intracellular nucleotides on the ATP-sensitive K+ (KATP) channel composed of SUR2A and Kir6.2 in HEK293T cells were examined using the patch-clamp technique. The SUR2A/Kir6.2 channel was activated effectively by pinacidil, marginally by nicorandil but not by diazoxide. The pinacidil-activated channel currents were inhibited by glibenclamide with a Ki value of 160 nM. Upon formation of inside-out (I-O) patches, spontaneous openings of the channels appeared, which were inhibited by intracellular ATP (ATPi) equipotently in the presence and in the absence of intracellular Mg2+ (Mg2+i). The channel activity ran-down gradually in I-O patches. The run-down channels could be reactivated by ATPi only in the presence of Mg2+i. Uridine 5'-diphosphate (UDP) antagonized the ATPi-mediated inhibition of the channel activity before run-down. After run-down, UDP activated the channel without antagonizing ATPi-mediated channel inhibition. Thus, the SUR2A/Kir6.2 reproduced the major properties of the native cardiac KATP channel well in terms of nucleotide regulation and pharmacology, and therefore can be a useful tool with which to elucidate the molecular mechanisms characterizing the KATP channel.

ATP-Binding Cassette Transporters↗
PubMed1984

Infection of a restrictive cell line (XC cells) by intratypic recombinants of HSV-1: relationship between penetration of the virus and relative amounts of glycoprotein C.

The ability to induce the synthesis of virus polypeptides in nonpermissive XC cells by several strains, variants, and intratypic recombinants of HSV-1 has been investigated. Our results show that (i) whereas HSV-1 strains mP and MP, and recombinants F(MP)A through D (Ruyechan et al., J. Virol. 29, 677-697, 1979) and HFEMtsB5/MP3 (Manservigi et al., Proc. Nat. Acad. Sci. USA 74, 3913-3917, 1977) induced in XC cells the synthesis of several virus polypeptides (the "positive" viruses), in the case of HSV-1 strain F, variants HFEMtsB5 and mPtsHA1 (both tested at 33 degrees), and recombinants F(MP)E and F(MP)F, no virus specific polypeptides could be detected in these cells (the "negative" viruses). (ii) Failure of the "negative" viruses to synthesize polypeptides in XC cells could be explained by failure of the virions to penetrate the cells since polyethylene glycol, a fusion promotor agent, enabled these viruses to overcome the blockage of their expression. (iii) The ability to modulate penetration into XC cells is genetically determined. A locus affecting this function maps between coordinates 0.70 to 0.82 of HSV-1 DNA and is closely linked to Cr, a locus controlling the synthesis or accumulation of virus glycoprotein C (gC) (Ruyechan et al., 1979). (iv) A decrease in the amount of gC, relative to gB, is associated with an enhanced ability to enter XC cells, suggesting that gC may control penetration into these restrictive cells by negatively modulating the gB promoted fusion between host cell and virion membranes.

Animals↗
PubMed2000

K(+) channel-blocking alkoxypsoralens inhibit the immune response of encephalitogenic T line cells and lymphocytes from Lewis rats challenged for experimental autoimmune encephalomyelitis.

Alkoxypsoralens, known as DNA photomodifying agents, have been shown to block voltage-dependent K(+) channels (Kv) as well as to alleviate functional deficits in certain multiple sclerosis (MS) patients in a manner similar to 4-aminopyridine. Since Kv channel blockers are known to inhibit T cell-mediated immune responses both in vitro and in vivo, we investigated the effects of three alkoxypsoralens, 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), and 5,8-diethoxypsoralen (H37), on the following parameters: (1) whole-cell K(+) currents of encephalitogenic, myelin basic protein-specific memory T cell line cells (MBP-TCLC) derived from Lewis rats as measured by patch-clamp technique, (2) proliferation of MBP-TCLC and lymph node cells (LNC) from Lewis rats challenged for experimental autoimmune encephalomyelitis (EAE) by immunisation with spinal cord homogenate as measured by 3H-thymidine incorporation, (3) interferon-gamma (IFN-gamma) secretion of MBP-TCLC as measured by ELISA, and (4) IFN-gamma gene expression of LNC as measured by quantitative reverse transcription polymerase chain reaction (RT-PCR) with ELISA-detection. The examined alkoxypsoralens exhibited suppressive effects on the measured parameters with the same sequence of efficacy: H37>5-MOP>8-MOP. We, therefore, conclude that Kv channel-blocking alkoxypsoralens interfere with voltage-controlled signal transduction in lymphocytes and might thereby suppress immune responses in autoimmune diseases of the central nervous system and most likely also in other autoimmune disorders. Thus, alkoxypsoralens, especially the non-phototoxic substance H37, are new candidates for further studies on K(+) channel blocking immunosuppressive drugs. The agents may exert a dual beneficial effect on demyelinating diseases like MS, because they could attenuate the inflammatory process and improve axonal conductivity.

4-Aminopyridine↗