Divergent cell cycle kinetics underlie the distinct functional capacity of mucosal T cells in Crohn's disease and ulcerative colitis.

Background: Different abnormalities of T cell effector function distinguish Crohn's disease (CD) from ulcerative colitis (UC). Because cell cycling determines effector function, pathogenic events in CD and UC may depend on cell cycle changes unique to each condition.

Methods: Cell cycle kinetics, cycle regulatory molecule expression, apoptosis, caspase and telomerase activity, and cellular expansion were evaluated in CD2 and CD3 activated control, CD, and UC lamina propria T cells.

Dual function of the extracellular matrix: stimulatory for cell cycle progression of naive T cells and antiapoptotic for tissue-derived memory T cells.

Tissue T cells encounter Ag in a distinct microenvironment, where they are embedded in the interstitial extracellular matrix (ECM). In contrast, while naive T cells are exposed to Ag in the lymph node, immediately after naive T cells are activated they must extravasate into the ECM to function effectively. Because integrin-mediated adhesion to the ECM modulates cell cycle progression and survival in adherent nonimmune cells, we hypothesize that blood and tissue-derived T cells have similarly adapted their behavior to their first or continued encounter with ECM.

The activation status of neuroantigen-specific T cells in the target organ determines the clinical outcome of autoimmune encephalomyelitis.

The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature of the target autoantigen and the genetic background of the experimental animals. Potentially lethal EAE is mediated by myelin basic protein (MBP)-specific T cells in Lewis rats, whereas transfer of S100beta- or myelin oligodendrocyte glycoprotein (MOG)-specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease. However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat.

Extracellular matrix conditions T cells for adhesion to tissue interstitium.

The activation and differentiation of peripheral blood T cells (PBT) are known to correlate with increased surface expression and adhesive capacity of beta(1) integrins, which mediate adhesion to the extracellular matrix (ECM). However, little is known about the regulation of integrin expression, affinity, and avidity on tissue T cells after they are embedded in the interstitial ECM. In this study we show that tissue T cells, freshly isolated from their residence in the interstitial ECM of the intestinal lamina propria, express a distinct subset of functionally active integrins that contribute to enhanced adhesion to purified collagen, fibronectin, and cell-derived ECM when compared with freshly isolated, short term activated, and long term cultured PBT.

Monocyte chemoattractant protein (MCP)-1 is rapidly expressed by sympathetic ganglion neurons following axonal injury.

EDI-immunoreactive macrophages, absent from the superior cervical ganglia (SCG) of normal rats, appear in these ganglia within 48h after postganglionic axotomy. Further, resident macrophages show changes after axotomy. Since chemokines function as chemoattractants and activators of leukocytes, the effects of axotomy on chemokine expression in the SCG were examined.

Role of chemokines, neuronal projections, and the blood-brain barrier in the enhancement of cerebral EAE following focal brain damage.

The role of focal brain damage as a trigger for autoimmune inflammation in multiple sclerosis (MS) is unclear. In this study we examine mechanisms by which experimental autoimmune encephalomyelitis (EAE) is enhanced by focal brain damage. EAE was produced in Lewis rats by footpad inoculation; focal brain damage, in the form of a cortical cryolesion (cryolesion-EAE), was induced 8 days post-inoculation (d.

Sequential expression of chemokines in experimental autoimmune neuritis.

Recruitment of inflammatory cells is of critical importance in the pathogenesis of immune-mediated demyelinating diseases in the peripheral nervous system (PNS). Evidence is increasing that chemokines might play a key role in this process, since they promote leukocyte entry into the nervous system during immune-mediated inflammation. In the present study we report the expression pattern of the chemokines interferon-gamma-inducible protein (IP)-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and regulated upon activation normal T cell expressed and secreted (RANTES) in sciatic nerves from animals with myelin-induced experimental autoimmune neuritis, using a semiquantitative reverse transcriptase-PCR dot-blot hybridization assay.

Biphasic and regionally-restricted chemokine expression in the central nervous system in the Theiler's virus model of multiple sclerosis.

Intracerebral infection of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) induces a biphasic disease characterized by acute polioencephalitis followed by chronic demyelination and viral persistence in the spinal cord white matter. There has been limited study of soluble mediators responsible for the initial recruitment of inflammatory cells into the gray matter, and the secondary influx into the white matter during infection with TMEV. We used sensitive and specific RT - PCR/dot blot hybridization assays to quantitate the relative levels of chemokine mRNA in the brains and spinal cords during the acute and chronic phases of TMEV infection in mice susceptible (B10.

Altered expression and activity of topoisomerases during all-trans retinoic acid-induced differentiation of HL-60 cells.

Regulation of topoisomerase II (TOPO II) isozymes alpha and beta is influenced by the growth and transformation state of cells. Using HL-60 cells induced to differentiate by all-trans retinoic acid (RA), we have investigated the expression and regulation of TOPO II isozymes as well as the levels of topoisomerase I (TOPO I). During RA-induced differentiation of human leukemia HL-60 cells, levels of TOPO I remained unchanged, whereas the levels and phosphorylation of TOPO IIalpha and TOPO IIbeta proteins were increased twofold to fourfold and fourfold to eightfold, respectively.

Selective chemokine mRNA accumulation in the rat spinal cord after contusion injury.

Following traumatic injury to the spinal cord, hematogenous inflammatory cells including neutrophils, monocytes, and lymphocytes infiltrate the lesion in a distinct temporal sequence. To examine potential mechanisms for their recruitment, we measured chemokine mRNAs in the contused rat spinal cord, using specific and sensitive reverse transcriptase polymerase chain reaction (RT-PCR) dot-blot hybridization assays. The neutrophil chemoattractant GRO-alpha was 30-fold higher than control values at 6 hr postinjury and decayed rapidly thereafter.

Cellular events involved in the sensitization of etoposide-resistant cells by inhibitors of calcium-calmodulin-dependent processes. Role for effects on apoptosis, DNA cleavable complex, and phosphorylation.

Inhibitors of calcium-calmodulin-dependent processes, 1-[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-piperazine KN-62 and trifluoperazine (TFP), at non-cytotoxic concentrations (2 and 5 microM, respectively) enhanced etoposide (VP-16) cytotoxicity in Adriamycin-resistant (HL-60/ADR0.05) cells (3- to > 50-fold). In contrast to TFP, the inhibitor KN-62 was able to reverse resistance in HL-60/ADR0.

Comparison of haptoglobin and apolipoprotein A-I on biliary lipid particles involved in cholesterol crystallization.

Several proteins are known to modulate cholesterol crystallization. We recently demonstrated that haptoglobin has cholesterol crystallization promoting activity. However, this effect is still not well understood mechanistically.

Resistance to etoposide in human leukemia HL-60 cells: reduction in drug-induced DNA cleavage associated with hypophosphorylation of topoisomerase II phosphopeptides.

Tumor cell resistance to anthracyclines and epipodophyllotoxins can be due to reduced drug accumulation and/or alterations in the activity of topoisomerase II (TOPO II). HL-60 cells selected in 0.05 micrograms/ml doxorubicin (DOX) are 10-fold and > 20-fold resistant to DOX and etoposide (VP-16), respectively.