Fibroblasts

Lewandowska K, Balachander N, Sukenik C N and Culp L A 1989 Modulation of fibroneotin adhesive funotions for fibroblasts and neural sells by ohemioally derivatized substrates J. Cell Physiol. 141 334-45... 

One possible mechanism responsible for the abiHty of trenbolone acetate to stimulate skeletal muscle hypertrophy may be through enhanced proliferation and differentiation of satelHte ceUs as the result of increased sensitivity to insuHn-Hke growth factor-I (IGE-1) and fibroblast growth factor (43). 

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

Ah = Antibody IL = interleukin TNF =tumornecrosis factor INF = interferon LAK =lymphocyte-activated killer CSF =colony stimulating factors and FGF = fibroblast growth factor. 

Long-lasting vasoconstriction is produced by the ETs in almost all arteries and veins and several studies have shown that ET-1 causes a reduction in renal blood flow and urinary sodium excretion. ET-1 has been reported to be a potent mitogen in fibroblasts and aortic smooth muscle cells and to cause contraction of rat stomach strips, rat colon and guinea pig ileum. In the central nervous system, ETs have been shown to modulate neurotransmitter release. 

Tendons are composed of fibrous connective tissue. Tendon tissue is also formed by the fibroblast ceUs, similar to the way ligaments are formed. These fibroblast ceUs then further differentiate into other specialized ceUs known as fibrocytes. Mature fibrocytes are inactive and compose the ceUular portion of tendons. The function of the tendon is to attach muscles to bones and other parts. 

Phosphorothioates generally protect normal tissues more than tumors. Tumor protection reported in some animal studies can pardy be explained by physiological effects of the particular dmgs, which are specific to rodents (4). WR-2721 does not appear to protect human and most animal tumors, apparentiy because of the low availabiUty of the dmg to tumor cells (4). Many tumors appear to have a reduced capillary density (44), which may mean that these tumors have altered levels of alkaline phosphatase, the enzyme that converts WR-2721 to WR-1065. A reduced abiUty of thiols to protect the hypoxic cells characteristic of many tumors may also contribute to their selectivity for normal tissues. The observation that WR-1065 protects cultured normal human fibroblasts, but not fibrosarcoma tumor cells, suggests that additional factors may contribute to the selectivity of radioprotection by WR-2721 m vivo (18). 

A critical step in radioprotection involves the IL-1 receptors. Monoclonal antibodies to the type 1 IL-1 receptor block IL-l-induced radioprotection (167). Although this receptor is not present on BM cells, it is present on fibroblasts, which suggests that the effects of IL-1 on stem cells maybe largely indirect and mediated by stromal cell activation (168). Anti-IL-1 receptor (type 1) also sensitizes normal mice to the effects of TBI, which suggests that endogenous IL-1 has an intrinsic radioprotective role. IL-6 induction by IL-1, but not CSF levels, is inhibited, which supports the concept that G-CSF and GM-CSF are insufficient by themselves at radioprotecting stem cells and indicates a contributory role for IL-6. Anti-IL-6 antibody blocks IL-1 and TNF-induced radioprotection and also decreases the intrinsic radioresistance of mice, as does anti-TNF- a (169). 

A 2-h incubation with another PGE2 analogue, nocloprost (9P-chloro-DMPG) protects normal human fibroblasts but has no effect on the survival of colon adenocarcinoma cells exposed to 10 Gy (1000 rad) (218). Nocloprost protects against radiation-induced DSBs in normal cells but not in tumor cells. Moreover, incubation using nocloprost for 2 h after irradiation enhances the rate of DSB rejoining in fibroblasts but not in adenocarcinoma cells. These data possibly reflect a different distribution of PG receptors on the plasma membrane of the two cell types. 

Factor VII. This is a vitamin K-dependent serine protease that functions in the extrinsic coagulation pathway and catalyzes the activation of Factors IX and X. Factor VII is present constitutively in the surface membrane of pericytes and fibroblasts in the adventitia of blood vessels, vascular endothehum, and monocytes. It is a single-chain glycoprotein of approximately 50,000 daltons. 

One limitation of enzyme replacement therapy is the targeting of enzyme proteins to appropriate sites of substrate accumulation. Administration of a cholesterol esterase conjugated to albumin results in the degradation of pathologic cholesterol ester accumulations within the lysosomes of fibroblasts from a patient with cholesterol ester storage disease (246). 

In vitro cytotoxicity assays using isolated cells have been applied intermittently to cyanobacterial toxicity testing over several years." Cells investigated for suitability in cyanobacterial toxin assays include primary liver cells (hepatocytes) isolated from rodents and fish, established permanent mammalian cell lines, including hepatocytes, fibroblasts and cancerous cells, and erythrocytes. Earlier work suggested that extracts from toxic cyanobacteria disrupted cells of established lines and erythrocytes," but studies with purified microcystins revealed no alterations in structure or ion transport in fibroblasts or erythrocytes,... 

Interferons [alFN, piFN and ylFN]. Interferons are a family of glycosylated proteins and are cytokines which are produced a few hours after cells have been infected with a virus. Interferons protect cells from viral infections and have antiviral activities at very low concentrations ( 3 x 10 M, less than 50 molecules are apparently sufficient to protect a single cell). Double stranded RNA are very efficient inducers of IFNs. There are three main types of IFNs. The aIFNs are synthesised in lymphocytes and the piFNs are formed in infected fibroblasts. The a and P families are fairly similar consisting of ca 166 to 169 amino acids. Although ylFNs are also small glycosylated proteins (ca 146 amino acids), they are different because they are not synthesised after viral infections but are produced by lymphocytes when stimulated by mitogens (agents that induced cell division). 

Several of these IFNs of mouse and human lymphocytes and fibroblasts are available commercially and have been best prepared in quantity by recombinant DNA procedures because they are produced in very small amounts by the cells. The commercial materials do not generally require further purification for their intended purposes. [Pestkas, Interferons and Interferon standards and general abbreviations. Methods Enzymol, Wiley Sons, 119 1986, ISBN 012182019X Lengyel, Biochemistry of interferons and their actions, Ann Bev Biochem 51 251-282 7982 De Maeyer and De Maeyer-Guignard, Interferons in The Cytokine Handbook, 3rd Edn, Thomson et al. Eds, pp. 491-516 7998 Academic Press, San Diego, ISBN 0126896623.]... 

Protease nexin (From cultured human fibroblasts) [148263-58-5], Purified by affinity binding of protease nexin to dextran sulfate-Sepharose. [Farrell et al. Biochem J 237 707 1986.]... 

VR Iyer, MB Risen, DT Ross, G Schuler, T Moore, JCF Lee, JM Trent, LM Staudt, J Hudson Jr, MS Boguski, D Lashkari, D Shalon, D Botstem, PO Brown. The transcriptional program m the response of human fibroblasts to serum. Science 283 83-87, 1999. 

Heparin was immobilized on the WPG-P A and the sorbent was used for isolation of the fibroblast growth factor from bovine hypophysis. Mitogenic activity of the factor purified on the heparin-WPG-PA and Heparin-Sepharose, as estimated with mice fibroblasts of line N1H-3T3, was virtually the same [130]. 

Fibroblasts, which are undifferentiated pre-adipo-cytes, can be stimulated and converted into adipocytes. 

Interferon (IFN) differs from bona fide antiviral diugs since it is a natural defense protein of the host organism and does not directly interfere with the viral replication steps. Interferons are small glycoproteins inducing immune modulatory and antiviral activities. They are secreted by lymphocytes, leukocytes and fibroblasts in response to foreign nucleic acids (dsRNA). 

Double stranded (ds) RNA is not a constituent of a normal cells but is produced during replication of many RNA and DNA viruses either as an obligatory intermediate or as a side product. As a foreign molecule, double stranded RNA induce the secretion of interferon (EFN) from lymphocytes, neutrophils and fibroblasts. 

ET-1 also stimulates anti-apoptotic signal cascades in fibroblasts, vascular smooth muscles and endothelial cells (via phosphatidylinositol-3-kinase and Akt/pro-tein kinase B). In prostate and ovarian cancer, upregulation of endothelin synthesis and ETA receptors has been associated with a progression of the disease. The inhibiton of ETA receptors results in a reduced tumour growth. In malignant melanoma, ETB receptors are associated with tumour progression. Endothelins can also stimulate apoptosis in stretch-activated vessels via the ETB receptor, which contrasts the above-mentioned effects. The molecular basis for these differential anti- and pro-apoptotic reactions mediated by endothelins remains elusive. 

---