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)

Human keratinocyte growth factor (KGF) is a recently identified mitogen for epithelial cells produced by normal stromal fibroblasts. KGF has been shown to stimulate keratinocyte migration and promote re-epithelialization of skin suggesting a critical role for KGF in wound healing. To understand how KGF might be regulated during wound healing, we examined the ability of the pro-inflammatory cytokines interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) transforming growth factor-beta 1 (TGF-beta 1) and interferon-gamma (IFN-gamma) to modulate KGF gene expression in cultured human fibroblasts, using northern blot analysis. Exposure to IL-1 alpha (20 units/ml) or IL-1 beta (100 units/ml) for 24 h increased KGF mRNA expression by 352% and 504%, respectively, with early induction seen at 2 h and maximal induction seen at 8 h. TNF-alpha (30 ng/ml) increased KGF mRNA expression by 535% at 24 h, with induction first seen at 8 h. The maximal induction of KGF mRNA was observed when IL-1 alpha, IL-1 beta and TNF-alpha were used at 100 units/ml, and 3 ng/ml, respectively, although concentrations 100-500-fold lower (IL-1 alpha, 0.02 units/ml; IL-beta, 0.02 units/ml; and TNF-alpha, 0.03 ng/ml) were nearly as stimulatory, increasing KGF mRNA expression by 175%, 254% and 322%, respectively. IL-6 (200 units/ml), TGF-beta 1 (5 ng/ml) and IFN-gamma (200 units/ml) did not change the level of KGF mRNA at 24 h in human fibroblasts under the same conditions. The protein synthesis inhibitor cycloheximide abrogated the effects of IL-1 alpha, IL-1 beta and TNF-alpha on KGF gene induction, indicating that new protein synthesis is required in the process. Dexamethasone (10(-7) M), known to inhibit inflammatory reactions and retard wound healing, also inhibited the induction of KGF mRNA expression by IL-1 alpha, IL-1 beta and TNF-alpha. Individual variation in KGF mRNA expression was see when fibroblasts from different aged donors were analysed, but no consistent age-associated change was observed. These results suggest that IL-1 alpha, IL-1 beta and TNF-alpha up-regulate KGF gene expression in fibroblasts and might be responsible for its induction following skin wounding or other injury.
J Dermatol Sci 1996 Jan
PMID:Regulation of keratinocyte growth factor gene expression in human skin fibroblasts. 886 66

Interferon-alpha combined with retinoid or PUVA is used for the treatment of cutaneous T-cell lymphoma. Anti-IFN-alpha antibodies (IFN ab) occur regularly during IFN-alpha treatment. We investigated the incidence of neutralizing and binding IFN ab and analysed their relationship with clinical and immunological parameters. A group of 17 CTCL patients were treated with IFN alpha-2a three times weekly subcutaneously at a dose of 3 Mill. I.U. combined either with retinoid (acitretin, Neotigason; 0.5 mg/kg bodyweight) daily or with 5-methoxypsoralen (1.2 mg/kg bodyweight) plus UVA radiation three times weekly. Prior to and during treatment we monitored stage, skin involvement by a tumour burden index, serum levels of beta 2-microglobulin, neopterin, binding and neutralizing IFN ab, Interleukin-6 (IL-6), soluble IL-2 receptors (sIL-2r) and the CD4/CD8 ratio of peripheral blood mononuclear cells. We observed two complete, two partial and six minor responses, four patients with stable disease and three patients with progressive disease. Of the 17 patients, 7 developed binding IFN ab, but only 2 had neutralizing IFN ab which were associated with high titres of binding IFN ab. IFN ab formation was more frequent in patients with normal CD4/CD8 ratios and a high tumour burden index and showed a trend to be more frequent in PUVA-cotreated patients than in retinoid-cotreated patients. Responses were more frequently seen in IFN ab-negative patients. IFN ab developed in patients treated with PUVA or retinoid combined with IFN. Binding as well as neutralizing IFN ab may have an impact on the treatment success in CTCL patients.
Arch Dermatol Res 1996 Aug
PMID:Incidence and in-vivo relevance of anti-interferon antibodies during treatment of low-grade cutaneous T-cell lymphomas with interferon alpha-2a combined with acitretin or PUVA. 887 50

Paraformaldehyde-fixed biopsy specimens of normal and chronic cutaneous leishmaniasis human skin were investigated for the presence and cellular distribution of interleukin-1 alpha, interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha and the corresponding receptors in eccrine sweat glands, using an indirect immunoperoxidase technique. There was cytoplasmic staining for all 4 cytokines as well as their receptor proteins in the clear cells of the eccrine sweat glands of both normal and inflamed skin specimens. No staining could be seen in the dark cells or the myoepithelial cells, neither in normal nor in inflamed skin. However, a difference between normal and inflamed skin was observed in the ductal system. Thus, cell layers of the dermal ducts in leishmaniasis skin were stained for all 4 cytokines, with more intense labelling in the basal cell layer of the coiled ducts, while in the normal skin, an intense staining was more evident in the inner luminal layer, with variable and less intense labelling of the basal layer. The immunolabelling for the cytokine receptors within the dermal ducts exhibited similar staining intensity in both luminal and basal cell layers, except in the case of the IL-6 receptor, which showed a moderate to intense signal in the basal cell layer but a weak staining of the luminal cell layer. Infiltrating inflammatory cells around the sweat gland apparatus in leishmaniasis skin exhibited immunoreactivities for all cytokines and their corresponding receptors.
Exp Dermatol 1996 Aug
PMID:Proinflammatory cytokines and their corresponding receptor proteins in eccrine sweat glands in normal and cutaneous leishmaniasis human skin. An immunohistochemical study. 888 71

A novel epithelioid sarcoma (ES) cell line, designated as ES-OMC-MN, was established from a 44-year-old woman with recurrence and metastasis of ES. The cells were spindle-shaped or polygonal and were positive for cytokeratin and vimentin on immunohistochemical staining. Electron microscopy revealed desmosome-like structures between the cells. These characteristics were also noted in the original tumor. Southern blot analysis of HindIII digests showed an additional 8.0 kb band and an 8.8 kb band in DNA from the cultured cells and the original tumor as well as the peripheral blood cells of the patient, while only an 8.8 kb band was observed in control human placental DNA. There were no point mutations of N-ras codons 12, 13, and 61, suggesting that the abnormality of N-ras was not due to mutation but to polymorphism. Interleukin-6 (IL-6) was secreted into the culture medium at high levels. Recombinant IL-6 augmented the proliferation of these cells, while cell growth was inhibited by incubation with an anti-IL-6 antibody. The cells also expressed surface IL-6 receptors, indicating that IL-6 acted on this cell line in an autocrine manner. IL-6 and IL-6 receptors were also found in the original tumor. These results demonstrate that ES-OMC-MN cells retained all the morphological and biochemical characteristics of the original tumor and suggest that an autocrine effect of IL-6 may be involved in the development of ES.
Arch Dermatol Res 1997 Mar
PMID:Establishment and characterization of an epithelioid sarcoma cell line with an autocrine response to interleukin-6. 914 39

Epidermal Langerhans cells are frequently anatomically associated with calcitonin gene-related peptide-containing nerves. Furthermore, calcitonin gene-related peptide inhibits Langerhans cells antigen-presenting function in several assays. Studies were performed to further explore the hypothesis that Langerhans cells and nerves have a functional relationship. To examine whether Langerhans cells may produce factors that influence nerve cell differentiation, we utilized the Langerhans cell-like cell line XS52 as a surrogate for Langerhans cells and compared it with Langerhans cells enriched to 90%. Supernatants conditioned by lipopolysaccharide-stimulated XS52 cells were able to induce the differentiation of the pheochromocytoma line PC12 into sympathetic neuron-like cells. This was also the case with enriched Langerhans cells stimulated by lipopolysaccharide. Pretreatment of conditioned supernatants with specific neutralizing anti-sera indicated that most of the differentiation-inducing activity was due to interleukin-6 and a small amount was due to nerve growth factor and basic fibroblast growth factor. By reverse transcriptase polymerase chain reaction, three clones of the XS52 cell line, XS52-4D, XS52-11D, and XS52-8B, were found to express mRNA for interleukin-6 and expression was markedly augmented by lipopolysaccharide. mRNA for nerve growth factor and basic fibroblast growth factor was detected in XS52-4D and XS52-11D, but not in XS52-8B. The expression of these neurotrophic factors by enriched Langerhans cells was quite similar to that of XS52-4D. In order to examine whether Langerhans cells may express receptors for nerve-derived peptides, reverse transcriptase polymerase chain reaction was employed to look for pituitary adenylate cyclase activating polypeptide type I, type II, and type III, and gastrin-releasing peptide receptors. All clones examined, as well as enriched Langerhans cells, expressed pituitary adenylate cyclase activating polypeptide type II and type III, and gastrin-releasing peptide receptors. These results suggest bi-directional signalling between Langerhans cells and nerves; nerve cells may regulate Langerhans cell function by elaboration of certain neuropeptides whereas Langerhans cells may promote the differentation of nerves by elaboration of interleukin-6 and, possibly, other factors.
J Invest Dermatol 1997 Oct
PMID:Expression of neurotrophic factors and neuropeptide receptors by Langerhans cells and the Langerhans cell-like cell line XS52: further support for a functional relationship between Langerhans cells and epidermal nerves. 932 95

Phosphatase activity on endothelial cell surfaces is responsible, in part, for the conversion of adenosine nucleotides to adenosine, a potent vasodilator and anti-inflammatory mediator that can protect tissues from the ischemic damage that results from injury. To evaluate whether phosphatases are actively induced by a soluble factor released following injury, the effect of tissue fluids collected from porcine or human skin wounds was tested on primary cultures of endothelial cells. Phosphatase activity increased approximately 50-fold following 48-h culture in the presence of wound fluid. Inductive activity was present only in fluids collected during the inflammatory phase of wound repair. The phosphatase activity metabolized adenosine monophosphate to free phosphate and was the liver/bone/kidney alkaline phosphatase isoenzyme: activity was temperature- and levamisole-sensitive, 1-phenylalanine-resistant, and linked to the cell surface via phospholipid, and migrated at a size identical to this isozyme. interleukin-6 was identified as the phosphatase-inducing factor in wound fluid and the related cytokines, leukaemia inhibiting factor, and oncostatin M, caused a similar degree of alkaline phosphatase induction. Therefore, following injury, accumulation of interleukin-6 can lead to production by alkaline phosphatase of adenosine and subsequent protection from ischemic injury.
J Invest Dermatol 1997 Oct
PMID:Endothelial cell surface alkaline phosphatase activity is induced by IL-6 released during wound repair. 932 97

Cutaneous plasmacytosis is a rare disorder without systemic plasma cell proliferation in organs other than the skin, with a possible malignant transformation. However, there are few effective therapies available. It has been reported that interleukin-6 (IL-6), which is a cytokine inducing B-cell differentiation to immunoglobulin-producing cells, plays a part in systemic plasmacytosis. In this study, we performed intralesional steroid therapy in the lesions of cutaneous plasmacytosis in three patients, which resulted in sufficient clinical effects. We demonstrated that before treatment, plasma IL-6 levels were significantly elevated in all the patients, and that levels were reduced in parallel with the clinical improvement after therapy. Immunohistochemistry revealed IL-6 protein expression on tumour cells in the lesional skin. Reverse transcription-polymerase chain reaction (RT-PCR) detected IL-6 mRNA in the lesional skin in all cases, levels of which were decreased after the effective intralesional steroid therapy, but which were unchanged after ineffective topical photochemotherapy (PUVA). Peripheral blood mononuclear cells from the patients produced significantly large quantities of IL-6 which were reduced by addition of steroid in vitro. These results suggest that the generation of IL-6 plays the key role in cutaneous plasmacytosis and that intralesional steroid therapy is effective in reducing the production of IL-6 in this disorder.
Br J Dermatol 1997 Oct
PMID:Increased plasma interleukin-6 in cutaneous plasmacytoma: the effect of intralesional steroid therapy. 939 Mar 45

Epidermal growth factor (EGF) family members and its receptor (EGFR) are thought to have an important role in the proliferation of epidermal keratinocytes. In this report, we investigated the EGF/EGFR system in primary keratinocytes derived from normal and psoriatic lesional skin. EGF elicited the growth of both normal human keratinocytes (NHKs) and psoriatic lesional keratinocytes (PLKs). Interleukin-6 (IL-6) potentiated the EGF-dependent growth of NHKs, but has no observable effect on PLKs, while IL-6 itself showed no growth-stimulating activities in both cell types. Immunodetection and in situ hybridization analyses revealed that IL-6 induces EGFR expression in NHKs in a time- and dose-dependent manner. This EGFR expression decreased reversibly to an undetectable level when IL-6-treated NHKs were re-cultured in IL-6-free conditions. On the other hand, PLKs expressed high levels of EGFR even when unstimulated and the expression level was not affected by IL-6 stimulation. These results suggest that the EGF/EGFR system is involved in the growth of NHKs and PLKs and that IL-6 potentiates NHK growth partly through the induction of EGFR. The different EGFR regulatory system may contribute to the pathogenesis of psoriasis.
J Dermatol Sci 1998 Jan
PMID:Different growth properties in response to epidermal growth factor and interleukin-6 of primary keratinocytes derived from normal and psoriatic lesional skin. 945 24

Several cytokines are increased in psoriatic skin, mainly at the lesional level. Some of these mediators seem to be very important in the pathogenesis of psoriasis since they are thought to stimulate keratinocyte proliferation and/or to drive the inflammatory changes associated with psoriasis. Among the proinflammatory modulators, hematopoietins, which are a family of cytokines sharing a receptor component (the gp130 subunit), have been under intensive investigation in recent years. The hematopoietin family includes interleukin-6 (IL-6), interleukin-11 (IL-11,) leukemia inhibitory factor (LIF), oncostatin-M (OSM), granulocyte colony-stimulating factor (G-CSF), ciliary neurotrophic factor (CNTF) and cardiotrophin. Amounts of two of these molecules, IL-6 and IL-11, have been found to be increased in psoriatic lesions. The present study adds new information concerning the spontaneous release of two hematopoietins, namely LIF and OSM, in 48-h culture supernatants of lesional and nonlesional skin punch biopsies from psoriatic patients and normal subjects. The cytokine determinations were performed using commercially available ELISA kits. The results are expressed as picograms per milligram of tissue, after weight normalization. The levels of LIF released by lesional skin (median 2.4 pg/mg, range 0.05-13.4 pg/mg) were significantly higher than from nonlesional (median 0.4 pg/mg, range under detection limit (UDL)-4.4 pg/mg; P = 0.001) and normal skin (median 0.4 pg/mg, range UDL-0.9 pg/mg; P = 0.005). The OSM levels were also significantly higher in supernatants of lesional skin (median 0.9 pg/mg, range 0.4-5.2 pg/mg) than in supernatants of nonlesional (median 0.2 pg/mg, range UDL-0.8 pg/mg; P = 0.001) and normal skin (median 0.1 pg/mg, range UDL-0.4 pg/mg; P = 0.0001). In addition, interleukin-8 (IL-8), a cytokine involved in the pathomechanisms of psoriasis, showed a similar behaviour when measured in the same samples. Lesional skin showed a median value of 752.5 pg/mg, range 98.8-2063.8 pg/mg, nonlesional skin a median value of 58.3 pg/mg, range UDL-1252.5 pg/mg (P = 0.007) and normal skin a median value of 44.6 pg/mg, range UDL-176.7 pg/mg (P = 0.004). No significant differences were found between nonlesional and normal skin for the three molecules analyzed. Taken together with the fact that at least two other hematopoietins (namely IL-6 and IL-11) are also increased in supernatants of lesional psoriatic skin, these data point to a possible involvement of the hematopoietins in inflammatory processes associated with psoriasis.
Arch Dermatol Res
PMID:Spontaneous release of leukemia inhibitory factor and oncostatin-M is increased in supernatants of short-term organ cultures from lesional psoriatic skin. 952 95

1,25-dihydroxyvitamin D3 (1,25-D3) modulates lymphocyte and macrophage functions in vitro. These effects are exerted through production of 1,25-D3 by antigen-presenting monocytes/macrophages (MO) and binding to vitamin D receptors expressed in MO and in activated, but not in resting T-lymphocytes. 1,25-D3 inhibits production of MO-derived cytokines such as interleukin-1 alpha, interleukin-6, and tumor necrosis factor alpha at the post-transcriptional level, most likely by reducing the half-life of specific mRNAs. The proliferation of T-cells and their release of cytokines such as IL-2 and interferon gamma are also suppressed by 1,25-D3, partly as a result of the reduced production of T-cell-activating cytokines (interleukin-1 alpha, tumor necrosis factor alpha), but also because of a direct effect on the T-cells. Although 1,25-D3 has no apparent effect on B-lymphocytes, the T-cell suppression indirectly inhibits antibody production by B-cells. The CD45R0+ subset of T-helper cells is relatively more sensitive than the CD45RA+ subset to the inhibitory effects of 1,25-D3. The CD45R0+ subset plays a key role in immune activation and in the pathogenesis of many autoimmune disease. 1,25-D3 acts as an important local regulator of T-cell functions and thus modulates several immunological effector functions. The actions of 1,25-D3 are distinct from those of commonly used immunosuppressants, and vitamin D3 analogs are therefore potentially useful as alternatives to conventional immunosuppressive therapies.
J Investig Dermatol Symp Proc 1996 Apr
PMID:1,25-Dihydroxyvitamin D3 as a natural regulator of human immune functions. 962 96


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>