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

Biologic dressings are believed to stimulate wound healing in a variety of wound types. Cryopreserved allograft skin (CAS) is used as a biologic dressing for excised wounds, partial-thickness wounds, and meshed split-thickness skin grafts, and the use of allogenic or autologous cultured epithelial sheets (CES) has been reported to enhance healing of skin ulcers and deep partial-thickness wounds. However, limitations of allograft skin include bacteriologic and viral safety, limited availability, cost, and ease of handling. Previously we have reported the successful use of human keratinocytes cultured to single-layer confluence on Hydroderm polyurethane membranes (HD/HK) for grafting of full-thickness wounds. In this study we evaluated the release of five different growth peptides (transforming growth factors alpha and beta (TGF-alpha, TGF-beta), interleukin-6, interleukin-8, and melanoma growth stimulatory activity from CAS, CES, and HD/HK grafts. Highest levels of TGF-alpha were found for HD/HK (728 +/- 115 pg/10 cm2 of membrane) followed by CES (491 +/- 137 pg/10 cm2; NS). No TGF-alpha was detectable for CAS, and 3.7-fold, and 25-fold higher levels of interleukin-6 were found for CES (257 +/- 12.7 U/10 cm2) compared with HD/HK and CAS, respectively. Interleukin-8 had similar levels for CES (0.65 +/- 0.7 ng/10 cm2) and HD/HK (0.88 +/- 0.12 ng/10 cm2), whereas melanoma growth stimulatory activity was elevated in CES (2314 +/- 97 pg/10 cm2) compared with HD/HK (1071 +/- 55 pg/10 cm2). TGF-beta was barely detectable for CES and HD/HK. Cryopreserved allograft showed high levels of TGF-beta (5.2 +/- 1.6 ng/10 cm2). Overall mitogenic activity of the supernatants on keratinocyte cultures was assessed. Highest proliferation was seen for CES supernatants followed by HD/HK (NS). Supernatants from CAS had an antiproliferative effect on keratinocytes. We conclude that a single layer of keratinocytes cultured on a polyurethane membrane facilitates keratinocyte proliferation similar to CES, whereas cryopreserved allograft has no mitogenic effect on keratinocytes.
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PMID:Growth peptide release from biologic dressings: a comparison. 895 39

In order to investigate the role of neural regulation in corneal epithelial healing, we examined the effect of substance P (SP) on corneal epithelial migration using an organ culture system of rabbit corneas. We investigated the synergistic effects of SP with (1) growth factors: epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta(TGF-beta); (2) extracellular matrix proteins: fibronectin, vitronectin, laminin, and collagen type IV; and (3) cytokines: interleukin-1alpha (IL-1alpha), IL-1beta, and interleukin-6 (IL-6). Rabbit corneal blocks were cultured in the absence or presence of various reagents for 24 hr. The corneal blocks were then fixed, dehydrated, embedded in paraffin and stained by hematoxylin-eosin, and the length of the path of epithelial migration was measured. The addition of SP alone, at concentrations up to 50 microg ml-1, did not affect epithelial migration. EGF, fibronectin, vitronectin, collagen type IV, and IL-6 stimulated epithelial migration, but bFGF, TGF-beta, laminin, IL-1alpha, and IL-1betadid not. The stimulatory effect of EGF on the epithelial migration was enhanced by the presence of SP. This synergistic effect of SP and EGF on corneal epithelial migration was abolished by the addition of an SP antagonist or enkephalinase. Other neurotransmitters (vasoactive intestinal peptide, calcitonin gene-related peptide, acetylcholine chloride, norepinephrine, serotonin) and tachykinins (neurokinin A, neurokinin B, kassinin, eledoisin, physalaemin) were examined, but none exhibited a synergistic effect with EGF. Interestingly, EGF alone stimulated the incorporation of 3H-thymidine into corneal epithelial cells, but the addition of SP with EGF did not enhance this effect. These results demonstrate that SP enhanced the EGF stimulation of corneal epithelial migration in vitro in a specific manner, suggesting a possible role of SP as a modulator of epithelial wound healing.
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PMID:Synergistic effect of substance P with epidermal growth factor on epithelial migration in rabbit cornea. 929 69

To determine which factors are useful for the risk assessment of man-made fibers, we examined the gene expression of proinflammatory cytokines, growth factors, manganese superoxide dismutase (MnSOD), and inducible nitric oxide synthase (iNOS) in mineral fiber-exposed rats by means of reverse transcription-polymerase chain reaction (RT-PCR). Male Wistar rats received a single intratracheal instillation of either saline (control) or two types of fibers (2 mg of Union Internationale Centre le Cancer (UICC) chrysotile or alumina silicate refractory ceramic fiber [RCF]). Expression of interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), platelet-deriving growth factor-A, (PDGF-A), platelet-deriving growth factor-B (PDGF-B), transforming growth factor beta 1 (TGF-beta 1), basic fibroblast growth factor (bFGF), MnSOD, and iNOS mRNA from lung and lipopolysaccharide (LPS)-stimulated alveolar macrophages (AM) were assessed by RT-PCR. Among these factors, IL-1 alpha, TNF-alpha, IL-6, bFGF, and iNOS would be the possible parameters for the risk assessment of fibers. In a follow-up study, we investigated the time course (3 days, 1 week, 1 month, and 3 months) of expression of IL-1 alpha and TNF-alpha by LPS-stimulated AM exposed to mineral fibers in vivo. Male Wistar rats were instilled intratracheally with saline or fibers (2 mg of Union Internationale Contre le Cancer UICC crocidolite or potassium octatitanate whisker [TW]). The expression of IL-1 alpha mRNA by fibers was greatest in TW, crocidolite, chrysotile, and RCF-instilled rat AM, in that order. The increase of IL-1 alpha and TNF-alpha mRNA in AM peaked at 1 month and 3 days after exposure to crocidolite or TW, respectively. The expression of IL-1 alpha by fibers (crocidolite, chrysotile, TW, and RCF) may be a good indicator of the pathologic potential of fibers.
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PMID:Effects of mineral fibers on the expression of genes whose product may play a role in fiber pathogenesis. 940 Jul 19

Plasma levels of interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta 1) were studied during cholecystokinin octapeptide (CCK-8)-induced regeneration after pancreas resection in rats. The weight of the pancreas and the DNA and protein contents increased significantly. The serum levels of TGF-beta 1 and IL-6 were increased significantly on days 7 and 14. There was no significant change in serum amylase levels. These findings indicate that cytokines such as TGF-beta 1 and IL-6 may play a role in the pathomechanism of pancreas regeneration.
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PMID:TGF-beta 1 and IL-6--new aspects in pancreas regeneration? 940 99

During the last few years, progress has been made towards the understanding of local regulation of bone remodelling especially in relation to osteoporosis. Cytokines have shown to be powerful regulators of bone resorption and formation, though under superior control from oestrogen/testosterone, parathyroidhormone and 1,25(OH)2D3. Some of the cytokines primarily enhance osteoclastic bone resorption e.g. IL-1 (Interleukin-1), TNF (Tumor Necrosis Factor) and IL-6 (Interleukin-6), while others primarily stimulate bone formation e.g. TGF-beta (Transforming Growth Factor), IGF (Insulin-like Growth Factor) and PDGF (Platelet Derived Growth Factor). Another category has complex functions with stimulation of bone formation in vitro but stimulation of bone resorption in vivo; IFN-gamma (Interferon-gamma) belongs to this category. The bone remodelling cycle is delicately regulated, and even a slight disturbance in this regulation can cause a pathological state in the bone such as osteoporosis. This paper will try to give a survey of some of the processes that regulate bone metabolism and hopefully contribute to understanding the changes in the remodelling related to osteoporosis.
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PMID:[Cytokines and osteoporosis]. 944 61

End-stage renal disease (ESRD) is more frequent in African Americans (blacks) compared to Caucasian Americans (whites). Identification of remediable causes of the increased prevalence has the potential to reduce the excess burden of ESRD. Because renal fibrosis is a correlate of progressive renal failure and a dominant feature of ESRD, and because transforming growth factor-beta 1 (TGF-beta 1) can induce fibrosis and renal insufficiency, we explored the hypothesis that TGF-beta 1 hyperexpression is more frequent in black ESRD patients compared to white ESRD patients. Our postulate was tested by determining circulating levels of TGF-beta 1 protein in the sera of 56 black and 42 white ESRD patients treated by chronic hemodialysis. A solid-phase sandwich enzyme-linked immunosorbent assay, specific for TGF-beta 1, was used to quantify TGF-beta 1 levels in the ESRD cohort. Additional cytokines implicated in tissue repair/remodeling, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), were also measured. Our investigation demonstrated a significantly higher concentration of TGF-beta 1 protein but not that of IL-6 or TNF-alpha in blacks compared to whites. Our observation that TGF-beta 1 is hyperexpressed in black ESRD patients suggests a mechanism for the increased prevalence of renal failure (since TGF-beta 1 hyperexpression can result in renal insufficiency in experimental models) among the black population.
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PMID:Transforming growth factor-beta 1 hyperexpression in African American end-stage renal disease patients. 950 29

Cytokines appear to play an important role in the development and progression of epithelial tumors. Cultured normal human thyroid follicular cells constitutively release high levels of interleukin-6 (IL-6) and IL-8, together with low to moderate levels of transforming growth factor-alpha (TGF-alpha) and TGF-beta. IL-6 appears to play multiple functions in thyroid physiology and disease. Because certain data indicate an inverse relationship between IL-6 production and epithelial tumor aggressiveness, we used both tissue culture methods and histochemical techniques to search for possible alterations of cytokine expression in thyroid carcinomas. As compared to cultures from normal tissue and well-differentiated carcinoma, production of IL-6 was strongly down-regulated in cultures derived from undifferentiated carcinoma. In contrast, levels of IL-8, TGF-alpha, and TGF-beta produced by neoplastic TFC were similar to those produced by normal cells. Actually, production of TGF-alpha was slightly enhanced in cultures from well-differentiated carcinoma. Immunoassay results were confirmed by reverse transcriptase-PCR analysis. Immunohistochemistry of human thyroid carcinomas (n = 99) and normal thyroid tissue (n = 85) showed that immunoreactive IL-6 was strongly diminished in undifferentiated forms (n = 34) and slightly reduced in well-differentiated carcinoma (n = 65). In agreement with the in vitro results, TGF-alpha expression was significantly increased in neoplastic thyrocytes, as compared to their normal counterpart. The results indicate that, as in the mammary and salivary glands, down-regulation of IL-6 expression may represent a marker of undifferentiated thyroid carcinoma.
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PMID:Reduced expression of interleukin 6 in undifferentiated thyroid carcinoma: in vitro and in vivo studies. 951 26

Tissue transglutaminase is a calcium-dependent, protein cross-linking enzyme that is highly expressed in cells undergoing apoptosis. The expression of tissue transglutaminase is regulated by a variety of molecules including retinoids, interleukin-6, and transforming growth factor-beta1 (TGF-beta1). Retinoid and interleukin-6 inductions of tissue transglutaminase expression are mediated by specific cis-regulatory elements located within the first 4.0 kilobase pairs of the promoter of the gene. The present studies were designed to identify the molecular mechanisms mediating the regulation of tissue transglutaminase gene expression by TGF-beta family members. Transient transfection of Mv1Lu cells with transglutaminase promoter constructs demonstrated that 0.2 nM TGF-beta1 maximally induced the activation of the promoter through a 10-base pair TGF-beta1 response element (TRE; GAGTTGGTGC) located 868 base pairs upstream of the transcription start site. This same element mediated an inhibitory activity of TGF-beta1 on the transglutaminase promoter in MC3T3 E1 cells. The TRE through which TGF-beta1-regulated the activity of the transglutaminase promoter was necessary and sufficient for bone morphogenetic protein 2- (BMP) and BMP4-dependent inhibition of the tissue transglutaminase promoter. The TGF-beta1, BMP2, and BMP4 regulation of the transglutaminase promoter activity was similar to the responses we observed for the endogenous transglutaminase activity of Mv1Lu and MC3T3 E1 cells. For BMP2 and BMP4, this regulation was paralleled by a decrease in tissue transglutaminase mRNA in MC3T3 E1 cells. The results of these experiments suggest that TGF-beta1, BMP2, and BMP4 regulation of mouse tissue transglutaminase gene expression requires a composite TRE located in the 5'-flanking DNA.
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PMID:Identification of a transforming growth factor-beta1/bone morphogenetic protein 4 (TGF-beta1/BMP4) response element within the mouse tissue transglutaminase gene promoter. 958 7

The mechanisms involved in normal cranial suture development and fusion as well as in the pathophysiology of craniosyostosis are not well understood. The purpose of this study was to investigate the expression of several cytokines--transforming growth factor-beta-1 (TGF-beta1), basic fibroblast growth factor (bFGF), and interleukin-6 (IL-6)--during cranial suture fusion. TGF-beta exists in three mammalian isoforms that are abundant in bone and stimulate calvarial bone formation when delivered locally. Other bone growth factors including basic fibroblast growth factor and the interleukins regulate bone growth and are mitogenic for bone marrow cells and osteoblasts. The involvement of growth factors in the pathophysiology of craniosynostosis is supported by recent genetics data linking fibroblast growth factor receptor mutations to syndromal craniosynostoses. In this experimental study, in situ hybridization was used to localize and quantify the gene expression of TGF-beta1, bFGF, and IL-6 during cranial suture fusion. In the Sprague-Dawley rat, the posterior frontal cranial suture normally undergoes fusion between 12 and 22 days of age, whereas all other cranial sutures remain patent. All in situ analyses of fusing posterior frontal sutures were compared with the patent, control, sagittal sutures. Posterior frontal and sagittal sutures, together with underlying dura, were harvested from rats at 8, 12, 16, and 35 days of postnatal life to analyze posterior frontal suture activity before, during, and after fusion. In situ hybridization was performed on frozen sections of these specimens using DNA probes specific for TGF-beta1, bFGF, and IL-6 mRNA. A negative control probe to IL-6 in the sense orientation was also used to validate the procedure. Cells expressing cytokine-specific mRNA were quantified (in cells positive per 10(-1) mm2) and analyzed using the unpaired Student's t test. Areas encompassing the fibrous suture and the surrounding bone plates were analyzed for cellular mRNA activity. IL-6 mRNA expression showed a minimal rise in the posterior frontal suture at days 12 and 16, with an average count of 10 and 6 cells per 10(-1) mm2, respectively. The sagittal suture remained negative for IL-6 mRNA at all time points. TGF-beta1 and bFGF analyses were most interesting, showing marked increases specifically in the posterior frontal suture during the time of active suture fusion. On postnatal day 8, a 1.5-fold increase in posterior frontal suture TGF-beta1 mRNA was found compared with sagittal sutures (p = 0.1890, unpaired Student's t test). This difference was increased 26-fold on day 12 in posterior frontal suture TGF-beta1 expression (p = 0.0005). By day 35, posterior frontal suture TGF-beta1 mRNA had nearly returned to prefusion levels, whereas TGF-beta1 mRNA levels in the sagittal suture remained low. A similar upregulation of bFGF mRNA, peaking at day 12, was observed in posterior frontal but not sagittal sutures (p = 0.0003). Furthermore, both TGF-beta1 and bFGF mRNA samples with intact dura showed an intense dural mRNA expression in the time preceding and during active posterior frontal suture fusion but not in sagittal tissues. Our data demonstrate that TGF-beta1 and bFGF mRNA are up-regulated in cranial suture fusion, possibly signaling in a paracrine fashion from dura to suture. TGF-beta1 and bFGF gene expression were dramatically increased both in and surrounding the actively fusing suture and followed the direction of fusion from endocranial to epicranial. These experimental data on bone growth factors support the recent human genetics data linking growth factor/fibroblast growth factor receptor deletions to syndromal craniosynostoses. The ultimate aim of these studies is to understand the underlying mechanisms regulating suture growth, development, and fusion so surgeons may one day manipulate the biology of premature cranial suture fusion.
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PMID:Studies in cranial suture biology: up-regulation of transforming growth factor-beta1 and basic fibroblast growth factor mRNA correlates with posterior frontal cranial suture fusion in the rat. 958 70

We have studied temporal mRNA expression patterns for interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), macrophage colony stimulating factor (M-CSF), and transforming growth factor-beta1 (TGF-beta1) in two rat injury paradigms with very different cellular inflammatory reactions: contussion of the spinal cord and axotomy of the facial nerve. Our comparative analyses using semiquantitative reverse transcription polymerase chain reaction (RT-PCR) show an early and robust upregulation of IL-1beta, TNF-alpha, IL-6, and M-CSF mRNAs in spinal cord after contusion injury. Peak expression of these mRNAs was transient and returned to control levels by 24 h postinjury. In contrast, expression of IL-1beta and TNF-alpha mRNAs in the axotomized facial nucleus was minimal and delayed, and levels of M-CSF mRNA remained unaltered. Similar to injured spinal cord, the axotomized nucleus showed a dramatic and early upregulation of IL-6 mRNA, but unlike spinal cord, IL-6 mRNA levels subsided only gradually. Both injury paradigms showed gradually increasing levels of TGF-beta1 mRNA which were maximal at 7 days postinjury. RT-PCR analyses were also performed on isolated blood-borne mononuclear cells and neutrophils. The results showed that these cells contain high levels of IL-1beta and M-CSF mRNAs, moderate levels of TGF-beta and TNF-alpha mRNAs, and minimal levels of IL-6 mRNA. The RT-PCR analyses together with histological observations indicate that expression of the proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6 is short-lived and self-limited after contusion injury, and that it occurs primarily within endogenous glial cells. Transient expression of these molecules likely triggers secondary events which may be beneficial to wound repair and regeneration.
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PMID:Cytokine mRNA profiles in contused spinal cord and axotomized facial nucleus suggest a beneficial role for inflammation and gliosis. 968 14


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