| 1. |
- Eklund, Erik, et al.
(författare)
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Proteoglycan production in disomic and trisomy 7-carrying human synovial cells.
- 2002
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Ingår i: Matrix Biology. - 1569-1802. ; 21:4, s. 325-335
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Tidskriftsartikel (refereegranskat)abstract
- To gain further insight into the synthesis and structure of the synovial matrix of joints, we have established cell cultures from synovial specimens and elaborated their production of hyaluronan and proteoglycans. The cultures secreted mainly the small proteoglycan decorin, but also considerable amounts of the related biglycan and the large proteoglycan versican. Only minor amounts of heparan sulfate proteoglycans were found. All cultures also had a high production of hyaluronan, which highlights the important role for normal joint function of these cells. In joint diseases, a common feature is the presence of an extra chromosome 7 (trisomy 7) in the synovial cells. To study the possible consequences of trisomy 7 on the synovial cell function, we extended our study to cultures that had been sub-cloned to contain high amounts of trisomy 7-carrying cells. These cell cultures had approximately four times more versican than their disomic counterparts in the cell culture medium, indicating that versican may be a mediator in the processes of joint destructive disorders. To find an explanation for this increase in versican, we investigated the expression/secretion of PDGF-AA and IL-6, cytokines with their genes located to chromosome 7. Indeed, both these cytokines were increased in the cultures with high frequencies of trisomy 7. We then added the two cytokines to cell cultures of disomic synovial cells, but only cells treated with IL-6 displayed an increased amount of versican. Thus, we suggest that the increased amount of versican in cultures of trisomy 7-carrying cells relates to an autocrine loop involving an increased IL-6 production.
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| 2. |
- King, Anne E., et al.
(författare)
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CD40 expression in uterine tissues: A key regulator of cytokine expression by fibroblasts
- 2001
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - 1945-7197. ; 86:1, s. 405-412
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Tidskriftsartikel (refereegranskat)abstract
- CD40 is a cell surface receptor initially discovered on cells of the hemopoietic lineage. Its primary role on immune cells is to enhance their activation and hence their production of cytokines and immunomodulatory molecules. Recently, CD40 has also been detected on human fibroblasts. An emerging view of the fibroblast is that it is far more than a structural cell, being capable of intimate interaction with cells of the immune system. In fibroblasts from several tissues, the engagement of CD40 with its ligand (CD40L) resulted in the secretion of proinflammatory molecules such as interleukin-6 (IL-6) and IL-8. Currently, there are few data about the presence of the CD40-CD40L system in female reproductive tissues. This study investigates the expression of CD40 by human endometrium, myometrium, and cenix both in situ and in tissue explant-derived fibroblasts. CD40 was detected mainly in the perivascular region of endometrium, myometrium, and cervix. Light staining for CD40 was observed in stromal elements. Additionally, the basal epithelium of cenix expressed CD40. Fibroblastic cells derived from all three sources express low levels of CD40, and this is up-regulated with interferon-gamma treatment (500 U/mL; 72 h). When activated with interferon-gamma and CD40L, the fibroblasts secreted increased amounts of IL-6, IL-8, and MCP-1. These data suggest that the CD40-CD40L system may provide a link between the resident structural cells of these reproductive tissues and the infiltrating immune cells or activated platelets that may express CD40L. The possible interaction of CD40 with CD40L may be particularly important during events such as menstruation and cervical ripening, where up-regulation of the proinflammatory molecules IL-6 and IL-8 is viewed as critical for these processes. In addition, dysregulation of this system may be a contributory factor to problems such as menstrual dysfunction and preterm labor.
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| 3. |
- Mazzucato, M, et al.
(författare)
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Vascular PG-M/versican variants promote platelet adhesion at low shear rates and cooperate with collagens to induce aggregation
- 2002
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Ingår i: FASEB Journal. - 1530-6860. ; 16:14, s. 1903-1916
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Tidskriftsartikel (refereegranskat)abstract
- We have identified a novel von Willebrand factor/fibrinogen/selectin-independent, platelet adhesion-promoting function of vascular PG-M/versicans that may be relevant in normal venous thrombosis and critical in atherosclerotic conditions. A purification scheme was devised to obtain vascular versicans, which by biochemical, immunochemical, and ultrastructural means were asserted to be 1) composed primarily of isoforms V1 and V2; 2) free of contaminants; 3) prevalently substituted with chondroitin-4-sulfate and dermatan sulfate (DS) chains; and 4) capable of binding hyaluronan to form link protein-stabilized ternary complexes. Real-time analysis of human platelet perfused under diverse shear forces showed that they largely failed to bind to several vascular and nonvascular proteoglycans (PGs). In contrast, they bound in a dose- and shear rate-dependent manner to vascular versicans, exhibiting a unique attachment-detachment kinetics and establishing a firm substrate tethering characterized with no significant aggregation. Digestion of these PGs with lyases and competition experiments with purified glycosaminoglycans revealed that platelet adhesion to vascular versicans was primarily mediated by their DS chains. Incorporation of the versicans into fibrillar collagen substrates augmented their adhesive activity and strongly promoted platelet aggregation at low and high shear rates. Affinity chromatography of platelet surfaces on DS columns identified a 120-140 kDa polypeptide complex that behaved as a specific vascular versican binding membrane ligand in solid-phase binding assays. These findings indicate that selective versican variants of the subendothelium may serve as ancillary GPIbalpha/integrin/selectin-independent platelet ligands in healthy and diseased vascular beds and may be directly responsible for the platelet accruing after rupture of atherosclerotic plaques., versican variants promote platelet adhesion at low shear rates and cooperate with collagens to induce aggregation.
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| 4. |
- Tornblom, SA, et al.
(författare)
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15-Hydroxyprostaglandin dehydrogenase and cyclooxygenase 2 messenger ribonucleic acid expression and immunohistochemical localization in human cervical tissue during term and preterm labor
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 89:6, s. 2909-2915
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Tidskriftsartikel (refereegranskat)abstract
- Here we have examined the enzymes cyclooxygenase (COX)-2 and 15-hydroxyprostaglandin dehydrogenase (15-OH PGDH) in pregnant human cervix. In biopsies taken transvaginally after preterm and term elective cesarean sections and vaginal deliveries, the levels of mRNA coding for COX-2 and 15-OH PGDH were assessed by Northern blotting. The cellular localization of the COX-2 and 15-OH PGDH proteins was determined by immunohistochemical analysis. COX-2 and 15-OH PGDH mRNAs were expressed at detectable levels in the cervical biopsies from all four groups of subjects. At cesarean sections ( unripe cervix), the level of 15-OH PGDH mRNA was significantly higher than the level in the ripe cervix at the time of partus, irrespective of the gestational length. In contrast, the level of COX-2 mRNA was similar in all subjects. Immunoreactivity of COX-2 and 15-OH PGDH was expressed by activated fibroblasts. The present investigation documents the expression and cellular localization of COX-2 and 15-OH PGDH in the preterm and term pregnant human cervix. This observation indicates that both preterm and term cervical ripening is associated with decreased degradation of prostaglandins.
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| 5. |
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| 6. |
- Xia, Guoqing, et al.
(författare)
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Heparan sulfate 3-O-sulfotransferase isoform 5 generates both an antithrombin-binding site and an entry receptor for herpes simplex virus, type 1
- 2002
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 277:40, s. 37912-37919
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate 3-O-sulfotransferase transfers sulfate to the 3-OH position of a glucosamine residue of heparan sulfate (HS) to form 3-O-sulfated HS. The 3-O-sulfated glucosamine residue contributes to two important biological functions of HS: binding to antithrombin and thereby carrying anticoagulant activity, and binding to herpes simplex viral envelope glycoprotein D to serve as an entry receptor for herpes simplex virus 1. A total of five HS 3-O-sulfotransferase isoforms were reported previously. Here we report the isolation and characterization of a novel HS 3-O-sulfotransferase isoform, designated as HS 3-O-sulfotransferase isoform 5 (3-OST-5). 3-OST-5 cDNA was isolated from a human placenta cDNA library and expressed in COS-7 cells. The disaccharide analysis of 3-OST-5-modified HS revealed that 3-OST-5 generated at least three 3-O-sulfated disaccharides as follows: IdoUA2S-AnMan3S, GlcUA-AnMan3S6S, and IdoUA2S-AnMan3S6S. Transfection of the plasmid expressing 3-OST-5 rendered wild type Chinese hamster ovary cells susceptible to the infection by herpes simplex virus 1, suggesting that 3-OST-5-modified HS serves as an entry receptor for herpes simplex virus 1. In addition, 3-OST-5-modified HS bound to herpes simplex viral envelope protein glycoprotein D. Furthermore, we found that 3-OST-5-modified HS also bound to antithrombin, suggesting that 3-OST-5 also produces anticoagulant HS. In summary, our results indicate that a new member of 3-OST family generates both anticoagulant HS and an entry receptor for herpes simplex virus 1. These results provide a new insight regarding the mechanism for the biosynthesis of biologically active HS.
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