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T H Piela-Smith

Publications and source records attributed to T H Piela-Smith.

9 recordsLinked to original sources
PubMed2001

Feverfew extracts and the sesquiterpene lactone parthenolide inhibit intercellular adhesion molecule-1 expression in human synovial fibroblasts.

Previous studies have shown that extracts of the aromatic herb feverfew (Tanacetum parthenium) and one of its bioactive components, parthenolide, have anti-inflammatory properties in vivo and in vitro. We examined both crude feverfew extracts and purified parthenolide for their ability to modulate adhesion molecule expression in human synovial fibroblasts. Pretreatment of synovial fibroblasts with either feverfew extracts or purified parthenolide could inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) induced by the cytokines IL-1 (up to 95% suppression), TNF-alpha (up to 93% suppression), and, less strongly, interferon-gamma (up to 39% suppression). Inhibition of ICAM-1 was dose and time dependent; as little as a 30-min pretreatment with feverfew resulted in inhibition of ICAM-1. The decrease in ICAM-1 expression was accompanied by a decrease in T-cell adhesion to the treated fibroblasts. Other herbal extracts with reported anti-inflammatory effects were similarly tested and did not decrease ICAM-1 expression. The modulation of adhesion molecule expression may be an additional mechanism by which feverfew mediates anti-inflammatory effects.

Anti-Inflammatory Agents↗
PubMed2000

Fibrin(ogen)-induced expression of ICAM-1 and chemokines in human synovial fibroblasts.

It has long been recognized that in most inflamed arthritic joints the coagulation system is activated, leading to the local generation of fibrin, and it has long been hypothesized that the local fibrin deposition promotes inflammation and tissue destruction. However, only recently has the direct effect of fibrin on the inflammatory process been seriously investigated, and specific roles assigned to fibrin or its products as mediators of the inflammatory process. Although fibrin and/or fibrinogen (fibrin(ogen)) is abundantly present in inflamed tissues and joints rich in fibroblastic cells, no significant data on fibrin(ogen)-induced gene expression by fibroblasts have been published. We now demonstrate that coculture of human synovial fibroblasts with fibrin(ogen) results in the up-regulation of ICAM-1 as well as increased production of the chemokines IL-8 and growth-related oncogene-alpha. Increased ICAM-1 expression was fibrin(ogen) dose-dependent and was demonstrated by ELISA, flow cytometry, and functional adhesion assays. Levels of ICAM-1 induced by fibrin(ogen) were comparable to those that could be induced by cytokine stimulation. Fibrin(ogen) stimulation of ICAM-1 could be suppressed by pyrrolidinedithiocarbamate, an inhibitor of NF-kappaB activation. Chemokine production was induced by fibrin(ogen) in cell culture supernatants >100-fold as compared with controls. Thus, through its activation of synovial fibroblasts, fibrin(ogen) deposition may promote the recruitment (via chemokines) and retention (via adhesion molecules) of lymphocytes within the arthritic joint.

Antioxidants↗
PubMed1997

Fibrin induction of ICAM-1 expression in human vascular endothelial cells.

In acute and chronic inflammatory processes, fibrin deposition, and leukocyte accumulation are classic histopathologic hallmarks. Previous studies have shown that fibrin and fibrin degradation products can have biologic effects on vascular endothelial cells and can induce the expression of several endothelial cell-derived factors that may be important in regulating inflammation and tissue repair. We now demonstrate that coculture of human vascular endothelial cells (EC) with fibrin results in the up-regulation of intercellular adhesion molecule-1 (ICAM-1), thus providing a first link between fibrin deposition and adhesion molecule expression, which may lead subsequently to leukocyte accumulation and extravasation. Increased ICAM-1 expression was demonstrated by ELISA, flow cytometry, and functional adhesion assays. EC ICAM-1 expression increased in a time and dose response fashion. Cell surface levels of ICAM-1 induced by fibrin were comparable to, or exceeded, levels induced by IL-1beta. ICAM-1 expression increased beginning at 4 h post-fibrin formation with sustained elevated expression at 48 h. Fibrin-stimulated EC also bound increased numbers of polymorphonuclear neutrophils in cellular adhesion assays. This increase in adhesion could be blocked by Ab to ICAM-1. Inhibition of fibrin polymerization also inhibited the up-regulation of ICAM-1. Culture medium from fibrin-stimulated EC contained elevated levels of soluble ICAM-1. These data suggest that fibrin deposition on vascular EC, in addition to other reported effects on EC metabolism, may also lead to leukocyte accumulation and extravasation through the induction of leukocyte adhesion molecules such as ICAM-1.

Cell Adhesion↗
PubMed1995

Aminopeptidase N: a constitutive cell-surface protein on human dermal fibroblasts.

Monoclonal antibodies were developed against human dermal fibroblast cell-surface membranes. Our goal was to find evidence of differential expression of antigens on fibroblast clones derived by limiting dilution. Antibodies were then used to isolate and identify membrane proteins. By sequence analysis of membrane immunoprecipitates, one monoclonal antibody, BR2, was subsequently shown to recognize the enzyme aminopeptidase N (hAPN; EC 3.4.11.2), originally described as a marker for certain hematopoetic cells. We have used biochemical techniques, electron microscopy, flow cytometry, and ELISA to characterize aminopeptidase N expression by human dermal fibroblasts. The presence of abundant aminopeptidase N confers enzymatic properties to human dermal fibroblasts which heretofore have been largely unexplored and suggest that the cellular distribution of aminopeptidase N is wider than originally appreciated.

Antibodies, Monoclonal↗
PubMed1994

Preferential adherence of human gamma delta, CD8+, and memory T cells to fibroblasts.

Fibroblasts and extracellular matrix produced by fibroblasts provide a framework within solid tissues to which lymphocytes can adhere. Lymphocyte adherence to this framework under basal and inflammatory conditions should contribute to retention of cells involved in innate and specific immunity. The purpose of this work was to determine whether all T cell subsets bind equally well to fibroblast cultures. T cells from healthy humans were co-cultured with autologous or allogenic dermal fibroblast cultures and adherent cells evaluated for surface markers. T cells adherent to untreated autologous fibroblast cultures were enriched for gamma delta T cells, with a striking increase in the V delta 1+ subpopulation. Exposure of the fibroblast cultures to rhIFN-gamma increased the number of adherent T cells and changed the pattern of adherence. Adherent T cells were further enriched for gamma delta T cells but not the V delta 1+ subset, and enriched for CD8+ and memory T cells. These findings suggest that T cell populations that bind to basal and stimulated fibroblast cultures are distinct. There were no qualitative differences in the binding of T cells to autologous and allogeneic fibroblast cultures.

Adult↗
PubMed1992

Regulation of ICAM-1 expression and function in human dermal fibroblasts by IL-4.

ICAM-1 is found on the surface of many hematopoietic and nonhematopoietic cells and can function as an adhesive ligand for the integrin, leukocyte function-associated molecule-1 (LFA-1, CD11a/CD18). ICAM-1/leukocyte function-associated molecule-1 interaction has been shown to be of importance in many immune-mediated cell-cell adhesion reactions. In vitro, unstimulated human fibroblast cell cultures express low levels of ICAM-1. Using ELISA, cytofluorography, electron microscopy, Northern analysis, and an in vitro cell adherence assay, we demonstrate that treatment of human dermal fibroblasts with the cytokine IL-4 leads to an increase in cell surface ICAM-1 expression that is under transcriptional control as well as increased fibroblast adhesion to LFA-1-bearing T lymphocytes. The kinetics of increased ICAM-1 expression induced by IL-4 paralleled the increase in ICAM-1-dependent T lymphocyte adhesion. The increase in T cell adhesion was determined to be due to the effects of IL-4 on the fibroblasts and not the adhering T cells. Treatment of fibroblasts with IL-4 also resulted in enhanced binding of human rhinovirus, a recently reported additional ligand for ICAM-1. Virus binding was IL-4 dose dependent and could be inhibited with mAb to ICAM-1. Both the expression of ICAM-1 and the ICAM-1-dependent increase in T lymphocyte adhesion that was induced by IL-4 could be inhibited by preexposure of the fibroblasts to either IL-1 or IL-6, suggesting that multiple cytokines can have both positive and negative effects on human fibroblast ICAM-1 expression and function.

Cell Adhesion↗
PubMed1992

Impairment of lymphocyte adhesion to cultured fibroblasts and endothelial cells by gamma-irradiation.

A critical component of immune responsiveness is the localization of effector cells at sites of inflammatory lesions. Adhesive molecules that may play a role in this process have been described on the surfaces of both lymphocytes and connective tissue cells. Adhesive interactions of T lymphocytes with fibroblasts or endothelial cells can be inhibited by preincubation of the fibroblasts or endothelial cells with antibody to intercellular adhesion molecule 1 (CD54) or by preincubation of the T cells with antibody to lymphocyte function-associated Ag 1 (CD11a/CD18), molecules shown to be important in several other cell-cell adhesive interactions. Here we show that gamma-irradiation of human T lymphocytes impaired their ability to adhere to both fibroblasts and endothelial cells. This impairment was not associated with a loss of cell viability or of cell surface lymphocyte function-associated Ag 1 expression. gamma-Irradiation of T cells is known to result in the activation of ADP-ribosyltransferase, an enzyme involved in DNA strand-break repair, causing subsequent depletion of cellular nicotinamide adenine dinucleotide (NAD) pools by increasing NAD consumption for poly(ADP-ribose) formation. Preincubation of T cells with either nicotinamide or benzamide [corrected], both known inhibitors of ADP-ribosyltransferase, completely reversed the suppressive effects of gamma-irradiation on T cell adhesion. The maintenance of adhesion was accompanied by inhibition of irradiation-induced depletion of cellular NAD. These experiments suggest that the impairment of cellular immune function after irradiation in vivo may be caused, in part, by defective T cell emigration and localization at inflammatory sites.

Adenosine Triphosphate↗
PubMed1991

Binding of human rhinovirus and T cells to intercellular adhesion molecule-1 on human fibroblasts. Discordance between effects of IL-1 and IFN-gamma.

Intercellular adhesion molecule-1 (ICAM-1) is found on the surface of many hemopoietic and non-hemopoietic cells and can function as an adhesive ligand for the integrin, leukocyte function associated molecule-1 (LFA-1, CD11a/CD18). ICAM-1/LFA-1 interaction is thought to be of importance in many immune mediated cell-cell adhesion reactions. Recently, the major human rhinovirus (HRV) receptor has been identified as ICAM-1. HRV has been shown to bind specifically to ICAM-1 on transfected COS cells and to purified ICAM-1, which has been adsorbed to plastic microtiter wells. We have compared the ability of ICAM-1 expressed on the surface of human fibroblasts (FB) to function as a receptor for HRV as well as a receptor for LFA-1-bearing human T lymphocytes. We show that FB stimulation by the cytokines IFN-gamma or IL-1, both known inducers of ICAM-1 synthesis and expression in FB, induced an increase in HRV binding to treated cells, which could be inhibited by antibody to ICAM-1. In contrast, only IFN-gamma and not IL-1 treatment of FB resulted in an increased adhesion of T lymphocytes. Binding of HRV to IFN-gamma-treated FB inhibited the subsequent adhesion of T cells. We also show that prior stimulation of FB with IL-1 enhanced the adhesion of HRV to IFN-gamma-stimulated cells, although IL-1 pretreatment was inhibitory for T cell adhesion. As these two cytokines both up-regulate ICAM-1 on the surface of human FB, the contrasting effects of IFN-gamma and IL-1 on human FB ICAM-1 adhesion to HRV and to LFA-1 suggest that qualitative as well as quantitative alterations of the ICAM-1 molecule may contribute to its specificity of ligand recognition.

Cell Adhesion↗