Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By interacting with a structurally identical receptor, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) display a common spectrum of action on the transport of mineral elements in bone and kidney. In vivo, PTH/PTHrP similarly reduce the renal tubular reabsorption of inorganic phosphate (Pi) and increase that of calcium. The hypercalcemic effect of PTHrP is due to an increase in both bone resorption and renal calcium reabsorption, the latter through a sodium-independent mechanism. The PTHrP-stimulated bone resorption can be totally inhibited by bisphosphonate therapy. Despite that, the fall in calcemia is moderate, indicating that the PTHrP main hypercalcemic action is due to the stimulation of the renal transport of calcium. For identical effects on renal ionic transports, PTHrP appears to less stimulate bone formation than PTH. These experimental findings are similar to clinical observations in patients with primary hyperparathyroidism or with solid malignant tumors. In vitro, the effects of PTH(1-34), PTHrP(1-34) and PTHrP(1-141) on cAMP production and sodium-dependent phosphate transport (NaPiT) are similar in kidney cells, where NaPiT is specifically inhibited by either peptide. This effect is attenuated by the competitive inhibitor [D-Trp12,Tyr34]bPTH(7-34)amide. Transforming growth factor-alpha similarly modulates the cAMP and NaPiT responses to PTH/PTHrP. In cultured mammary cells isolated from lactating rats, PTHrP elicits a 2-fold increase of cAMP production. Various products of bone and stromal cells, and of leukocytes, such as Interleukin-6 or Tumor necrosis factor-alpha, as well as high extracellular calcium concentration enhance PTHrP production by cultured lung squamous cell carcinoma and Leydig tumor cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Actions of parathyroid hormone and parathyroid hormone-related protein. 133 36

To identify factors that regulate proliferin (PLF) and PLF-related protein (PRP) secretion by the mouse placenta, placental cells from day 9 of pregnancy were cultured for up to 5 days, and PLF and PRP release into the medium was assessed by RIA. Transforming growth factor-alpha, interleukin-1 alpha, and interleukin-6 did not regulate either PLF or PRP secretion. However, treatment of primary placental cell cultures with 8-bromo-cAMP, cholera toxin, or forskolin resulted in 2- to 3-fold increases in the percentages of PLF- and PRP-producing cells in the population and corresponding increases in both PLF and PRP messenger RNA and secreted protein. The increase in the number of PLF-producing cells was accompanied by an increase in the number of cells expressing both PLF and mouse placental lactogen-I. These data suggest that cAMP levels can regulate trophoblast giant cell differentiation and, consequently, the amount of PLF and PRP secretion.
 ...
PMID:Cyclic adenosine 3',5'-monophosphate stimulation of placental proliferin and proliferin-related protein secretion. 772 Jun 52

Cancer remains the second most common cause of death in our society, and advanced disease is often refractory to surgical, chemotherapeutic, and radiologic interventions. One novel approach to cancer treatment involves targeting a cytotoxic agent to a cancer cell. Immunotoxins have been developed that contain a potent toxin (either Pseudomonas exotoxin, ricin toxin, or diphtheria toxin) coupled to a targeting moiety that directs the molecule to cells expressing a certain antigen. Chemically coupled immunotoxins have been developed over the past 12 years. These bind to and kill cells expressing many tumor-associated antigens. Initial clinical results were disappointing, but recent results have been more promising. Furthermore, newer immunotoxins have been developed that will soon be in clinical trials. Some of these are recombinant toxins that have been developed using techniques of genetic engineering. Transforming growth factor-alpha, acidic fibroblast growth factor, insulin-like growth factor-1, interleukin-2, interleukin-4, interleukin-6, the binding portions of monoclonal antibodies, and CD4 have been used to direct toxins to cancer cells or cells infected with the human immunodeficiency virus type 1. Efforts are under way to circumvent problems such as immunogenicity that may limit the clinical usefulness of immunotoxins.
 ...
PMID:Immunotoxins and recombinant toxins in the treatment of solid carcinomas. 836 39

Transforming growth factor-alpha (TGF-alpha) is produced in the lung in experimental and human lung diseases; however, its physiological actions after lung injury are not understood. To determine the influence of TGF-alpha on acute lung injury, transgenic mouse lines expressing differing levels of human TGF-alpha in distal pulmonary epithelial cells under control of the surfactant protein C gene promoter were generated. TGF-alpha transgenic and nontransgenic control mice were exposed to polytetrafluoroethylene (PTFE; Teflon) fumes to induce acute lung injury. Length of survival of four separate TGF-alpha transgenic mouse lines was significantly longer than that of nontransgenic control mice, and survival correlated with the levels of TGF-alpha expression in the lung. The transgenic line expressing the highest level of TGF-alpha (line 28) and nontransgenic control mice were then compared at time intervals of 2, 4, and 6 h of PTFE exposure for differences in pulmonary function, lung histology, bronchoalveolar lavage fluid protein and cell differential, and lung homogenate proinflammatory cytokines. Line 28 TGF-alpha transgenic mice demonstrated reduced histological changes, decreased bronchoalveolar lavage fluid total protein and neutrophils, and delayed alterations in pulmonary function measures of airway obstruction compared with those in nontransgenic control mice. Both line 28 and nontransgenic control mice had similar increases in interleukin-1beta protein levels in lung homogenates. In contrast, interleukin-6 and macrophage inflammatory protein-2 levels were significantly reduced in line 28 transgenic mice compared with those in nontransgenic control mice. In the transgenic mouse model, TGF-alpha protects against PTFE-induced acute lung injury, at least in part, by attenuating the inflammatory response.
 ...
PMID:Attenuation of acute lung injury in transgenic mice expressing human transforming growth factor-alpha. 1056 91