Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Topical application of 1alpha,25-dihydroxyvitamin D3 (VD3) is thought to be beneficial in psoriasis because of its action in regulating keratinocyte proliferation and inflammation mediated by various cytokines. We assessed the effect of VD3 on the production levels of interferon (IFN)-alpha, interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha in mitogen-stimulated peripheral blood mononuclear cells (PBMC) of psoriatic patients. The results demonstrated that VD3 significantly inhibited IFN- , IL-6, and IL-8 levels produced by concanavalin A (Con A)-stimulated PBMC of psoriatic patients in a dose-dependent manner, and reduced mRNA expression for IFN- and IL-8. These findings suggest that in addition to the direct anti-proliferation effect on keratinocytes, VD3 may down-regulate the inflammatory cytokine production by infiltrating cells in psoriatic lesions.
Eur J Dermatol
PMID:Regulatory effects of 1alpha,25-dihydroxyvitamin D3 on inflammatory responses in psoriasis. 964 61

Exposure of the skin to ultraviolet (UV) light causes DNA damage, inflammation, and impairment of local as well as systemic immune responses. Dermal microvascular endothelial cells are key elements for the recruitment of inflammatory cells during the pathogenesis of inflammatory skin diseases via the expression of adhesion molecules and the release of cytokines. Because UVB may directly affect the function of dermal cells it was investigated whether UVB irradiation alters the production of proinflammatory and chemotactic cytokines by endothelial cells. UVB exposure of transformed human microvascular endothelial cells (HMEC-1) resulted in a dose dependently increased mRNA expression as well as release of interleukin (IL)-1beta, IL-6, IL-8, and growth-regulated oncogene alpha (GROalpha). Maximum cytokine production was observed 16-24 h after irradiation when 7.5-12.5 mJ UVB per cm2 were used. In addition, it was examined whether IL-10, which is upregulated in keratinocytes following UVB irradiation and accounts for UV mediated immunosuppression such as inhibition of contact hypersensitivity, also affects endothelial cell cytokine production. Treatment of HMEC-1 with IL-10 significantly enhanced IL-6 and IL-8 release and further upregulated UVB-induced IL-6 and IL-8 mRNA expression. These findings demonstrate that UVB both directly and indirectly via the release of IL-10 stimulates microvascular endothelial cells to produce proinflammatory cytokines and chemokines that are required for the migration and activation of inflammatory cells in UV-mediated inflammatory skin reactions.
J Invest Dermatol 1998 Jul
PMID:Ultraviolet light and interleukin-10 modulate expression of cytokines by transformed human dermal microvascular endothelial cells (HMEC-1). 966 86

Epidermal infiltration by neoplastic CD4+ T cells is a characteristic histologic feature of early stage mycosis fungoides, the most common type of cutaneous T cell lymphoma (CTCL). The mechanisms involved in epidermotropism are unknown. It has been suggested that the CXC chemokines IL-8 and interferon-gamma inducible protein 10 (IP-10) may play a role, but evidence that these chemokines are produced within the epidermis in epidermotropic CTCL is lacking. In this study skin biopsies from 17 CTCL patients, including 12 mycosis fungoides, four pleomorphic CTCL, and one CD8+ CTCL, were investigated for epidermal IL-8 and IP-10 mRNA expression by RNA in situ hybridization. In addition, the expression of monokine induced by gamma-interferon (Mig) mRNA, a CXC chemokine closely related to IP-10, was studied as well. The expression of IL-8 receptors A and B (CXCR1 and CXCR2, respectively) was investigated by immunohistochemistry. The results were correlated with the number and phenotype of epidermotropic T cells. Epidermal expression of IP-10 and Mig mRNA was detected in 10 of 11 and seven of 11 epidermotropic CTCL, respectively, but not in five nonepidermotropic CTCL biopsies or normal human skin. Epidermal IP-10 and Mig mRNA expression correlated with epidermal infiltration of CD4+ T cells, but not of CD8+ T cells. IL-8 mRNA was demonstrated in the epidermis of only two of 15 CTCL biopsies, and was associated, in both cases, with accumulation of neutrophils. Consistently, immunostaining of the (intraepidermal) T cells with antibodies against CXCR1 and CXCR2 was not observed. In conclusion, the results of this study indicate that IP-10, and to a lesser extent Mig, but not IL-8 is involved in the preferential infiltration of neoplastic CD4+ T cells in CTCL.
J Invest Dermatol 1998 Aug
PMID:Epidermal interferon-gamma inducible protein-10 (IP-10) and monokine induced by gamma-interferon (Mig) but not IL-8 mRNA expression is associated with epidermotropism in cutaneous T cell lymphomas. 969 21

Keratinocytes are influenced by cytokines released by skin-infiltrating T lymphocytes. IL-17 is produced by activated CD4+ T cells and can stimulate epithelial cells. We investigated whether IL-17 could modulate the cytokine production and cell-surface molecule expression of keratinocytes. The effects of IL-17 were compared with those of IFN-gamma, which is also derived from activated T cells and is a strong stimulator for keratinocytes. IL-17 enhanced the mRNA and protein production of the proinflammatory cytokines IL-6 and IL-8 in a concentration-dependent way, and induced a weak expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR. The production of IL-1alpha and IL-15 was not altered. IFN-gamma augmented the production of IL-6, IL-8, and IL-15 and strongly induced both cell-surface molecules. IL-17 and IFN-gamma showed marked synergism in the stimulation of IL-6 and IL-8 protein secretion and, to a lesser extent, in the induction of ICAM-1 and HLA-DR expression. The majority of the CD4+ and CD8+ T cell clones derived from lesional psoriatic skin expressed IL-17 mRNA, suggesting that skin-infiltrating T cells can produce this cytokine. This IL-17 mRNA expression was detectable in T helper cell type 1 and type 2 and did not correlate with the IFN-gamma or IL-4 production. In addition, IL-17 mRNA is detectable in biopsies from lesional psoriatic skin, but not in nonlesional control biopsies. Our study indicates that IL-17 is a proinflammatory cytokine, which could amplify the development of cutaneous inflammation and may support the maintenance of chronic dermatoses, through stimulation of keratinocytes to augment their secretion of proinflammatory cytokines.
J Invest Dermatol 1998 Oct
PMID:Interleukin-17 and interferon-gamma synergize in the enhancement of proinflammatory cytokine production by human keratinocytes. 976 47

Interactions between infiltrating T cells and keratinocytes via the secretion of the TH1 cytokines interleukin (IL) 2 and interferon gamma (INF-gamma), the keratinocyte growth factor transforming growth factor alpha (TGF-alpha) and the cytokines IL-6 and IL-8 are thought to be the predominant mechanisms inducing skin lesions in psoriatic patients. Systemic treatment of psoriasis with fumaric acid derivatives (FAEs) has been reported to be effective in the treatment of psoriasis, but the mode of action is still unknown. To clarify this phenomenon, keratinocytes from psoriatic patients as well as from healthy volunteers were mono- and cocultured with HUT 78 T cells with/without the addition of FAEs; the cytokine concentrations were then measured in the culture supernatants. Furthermore, mRNA expression was determined in epidermal growth factor (EGF) -activated keratinocytes as well as in phytohaemagglutinin (PHA)-activated HUT 78 T cells. Only dimethylfumarate (DMF) diminished IL-6 and TGF-alpha secretion in the psoriatic cocultures. However, it did not have this effect on cocultures from control subjects or on monocultures. DMF suppresses EGF-induced TGF-alpha mRNA induction in psoriatic keratinocytes. DMF inhibited INF-gamma secretion in all cultures but stimulated the IL-10 secretion. This immunomodulation away from the TH1 cytokine IFN-gamma to the TH2 cytokine IL-10 was confirmed in HUT 78 T cells by Northern blot analysis. An increased number of eosinophils is a known side-effect in patients treated with this drug, suggesting a clinical relevance of this immunomodulation in vivo. This immunomodulation and the suppression of cytokines from the psoriatic cytokine network could be responsible for the beneficial effect of DMF in the treatment of a hyperproliferative and TH1 cytokine-mediated skin disease.
Br J Dermatol 1998 Sep
PMID:The antipsoriatic agent dimethylfumarate immunomodulates T-cell cytokine secretion and inhibits cytokines of the psoriatic cytokine network. 976 81

Ultraviolet (UV) irradiation of the skin induces complex local and systemic immunomodulatory reactions. The biological effects of UV irradiation on human skin derived afferent lymph however are unknown. The aim of this study was to examine the effects of a single combined UV-A and UV-B irradiation with 1 minimal erythema dose (MED) on human skin derived lymph in vivo. After cannulation of a superficial lymph vessel on the lower leg, lymph flow and cell output per hour were determined before and for 6 days after UV irradiation of the lymph draining skin area in 5 volunteers. Furthermore, expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells and cytokine levels (IL-1alpha, IL-1beta, IL-2, IL-6, IL-8, IL-10, IL-13, TNF-alpha and IFN-gamma) in the afferent lymph were analyzed by cytofluorometry and ELISA. After UV irradiation a small initial enhancement in the daily lymph flow per hour was noticed in correlation with the slight erythematous skin reaction. Following resolution of the skin reaction, a delayed increase in cell output in correlation with an additional peak in the lymph flow was found between the 4th and 6th day after UV irradiation. However, no changes in the expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells were detectable. Interestingly, in parallel to the increased lymph flow and cell output, only elevated IL-8 protein levels were reproducibly detected in the afferent lymph after UV irradiation. Furthermore, using immunohistochemistry positive staining for IL-8 was found on migrating mononuclear lymph cells. In conclusion, our data demonstrate that a single UV irradiation of the skin with 1 minimal erythema dose leads to a delayed enhancement of lymph flow, number of migrating lymph cells and cytokine levels of IL-8. Moreover, we provide evidence that migrating lymph cells, besides resident epidermal and dermal cells, may contribute to the detected levels of IL-8 in the afferent lymph.
Exp Dermatol 1998 Dec
PMID:Effects of UV irradiation with one minimal erythema dose on human afferent skin lymph in vivo. 985 39

Mast cells are traditionally viewed as effector cells of immediate type hypersensitivity reactions. There is, however, a growing body of evidence that the cells might play an important role in the maintenance of tissue homeostasis and repair. We here present our own data and those from the literature elucidating the possible role of mast cells during wound healing. Studies on the fate of mast cells in scars of varying ages suggest that these cells degranulate during wounding, with a marked decrease of chymase-positive cells, although the total number of cells does not decrease, based on SCF-receptor staining. Mast cells contain a plethora of preformed mediators like heparin, histamine, tryptase, chymase, VEGF and TNF-alpha which, on release during the initial stages of wound healing, affect bleeding and subsequent coagulation and acute inflammation. Various additional vasoactive and chemotactic, rapidly generated mediators (C3a, C5a, LTB4, LTC4, PAF) will contribute to these processes, whereas mast cell-derived proinflammatory and growth promoting peptide mediators (VEGF, FGF-2, PDGF, TGF-beta, NGF, IL-4, IL-8) contribute to neoangiogenesis, fibrinogenesis or re-epithelization during the repair process. The increasing number of tryptase-positive mast cells in older scars suggest that these cells continue to be exposed to specific chemotactic, growth- and differentiation-promoting factors throughout the process of tissue remodelling. All these data indicate that mast cells contribute in a major way to wound healing. their role as potential initiators of or as contributors to this process, compared to other cell types, will however have to be further elucidated.
Exp Dermatol 1999 Feb
PMID:Mast cells and their mediators in cutaneous wound healing--active participants or innocent bystanders? 1020 16

The increased number and early activation of cutaneous mast cells is a typical feature of psoriatic inflammation. Interferon-gamma (IFN-gamma) is believed to be one of the important mediators in the cytokine cascade of psoriasis. Human mast cells have been previously reported to release various cytokines upon stimulation including interleukin (IL) -4, IL-5, IL-6, IL-8, IL-13 and tumour necrosis factor-alpha. Here we report that human mast cells synthesize also IFN-gamma at mRNA and protein level and that the number of IFN-gamma producing mast cells is significantly increased in the psoriatic skin. IFN-gamma immunoreactivity in mast cells was demonstrated by staining non-lesional and lesional skin sections from 21 patients with psoriasis. Ten patients with atopic dermatitis (AD) and five healthy persons served as control groups. The percentage (mean +/- SD) of IFN-gamma + mast cells in lesional compared with non-lesional psoriatic skin was 67 +/- 18% vs. 44 +/- 17% (P < 0.0001, paired t-test), respectively, but only 9 +/- 6% vs. 10 +/- 7% in corresponding skin samples of AD. In the skin of healthy controls, only 12 +/- 12% of the mast cells were IFN-gamma +. Using immunoelectron microscopy, we confirmed the ultrastructural localization of IFN-gamma within the granules of mast cells in psoriatic skin. In addition, stimulation of a human mast cell line HMC-1 with phorbol myristate acetate (PMA) (100 nmol/L) for periods of 2-24 h induced expression of IFN-gamma mRNA, which peaked at 24 h. When HMC-1 cells were stimulated with PMA (100 nmol/L) for periods of 0-3 days, the cells released IFN-gamma protein, peaking on day 1. These results provide further evidence for the important role of mast cells in the pathogenesis of psoriasis.
Br J Dermatol 1999 Apr
PMID:Mast cells in psoriatic skin are strongly positive for interferon-gamma. 1023 11

Linear IgA bullous dermatosis (LAD) is an acquired, heterogeneous, subepidermal blistering disease characterized by linear IgA deposits at the dermoepidermal basement membrane zone (BMZ), often with circulating IgA antibodies to the BMZ. The pathogenetic mechanism, possibly related to the immunophenotype of infiltrating cells, as well as the potential role of cytokines in determining bullous lesions, have not yet been elucidated. An immunohistochemical study was performed with a large panel of monoclonal antibodies [to CD3, CD4, CD8, CD25, CD1a, CD30, CD54, CD50, endothelial leucocyte adhesion molecule-1, vascular cell adhesion molecule-1, myeloperoxidase (MPO), eosinophil cationic protein EG1 and EG2, tryptase, HLA-DR, human interleukin (IL)-3, human IL-5, human IL-8, human IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte/macrophage colony-stimulating factor] using the alkaline phosphatase-antialkaline phosphatase procedure on lesional and perilesional skin of nine patients (one male, eight female; age range 8 months-80 years) with clinical, histological and immunofluorescent proven LAD. The predominant infiltrating cells, distributed mostly inside and below the bullae, were neutrophils and eosinophils which showed intense activation (MPO +, EG1 +, EG2 +). The lymphocytic infiltrate, consisting principally of CD4 +, HLA-DR + and CD30 + T cells, had a predominantly perivascular distribution. Proinflammatory cytokines, such as TNF-alpha and IFN-gamma, showed a moderate focal expression on the dermal perivascular sites; IL-8 was found to have a particularly intense staining on all the epidermal cell layers and at perivascular and vascular sites. Other cytokines, such as IL-4 and IL-5, showed a prevalent intracytoplasmic staining on some cells of the dermal infiltrate (probably mastocytes and lymphocytes), and at the dermal-epidermal separation sites there was also an intense scattered distribution of IL-5. The specific tissue lesions of LAD may be the consequence of the IgA deposits at the BMZ and also of the release of these cytokines together with tissue damage enzymes derived from neutrophils or eosinophils.
Br J Dermatol 1999 Jun
PMID:The role of lymphocytes, granulocytes, mast cells and their related cytokines in lesional skin of linear IgA bullous dermatosis. 1035 73

The two photodermatoses, polymorphic light eruption (PLE) and chronic actinic dermatitis (CAD), are characterized by lymphocyte-rich inflammatory infiltrates, the pathogeneses of which are not fully understood. We have therefore studied suction blister fluid (SBF) samples from patients with these conditions before and at two time points after the induction of experimental lesions by means of a solar simulator; this SBF was then tested for the presence of selected cytokines known to induce peripheral blood lymphocyte (PBL) migration in vitro. A specific EL-4 NOB-1 bioassay was used to detect interleukin (IL)-1 activity, which has already been noted in normal skin and this was found in pre-irradiation control samples as well as 1-3 h and 24 h post-irradiation in both patient groups, but at levels not significantly different from those of controls. Use of a B9 cell proliferation assay showed no detectable IL-6-like activity pre-irradiation, but there was substantial activity in samples at both post-irradiation time points in both patient groups. Further, in other experiments, retained SBF samples were tested in an in vitro PBL migration assay in the presence and absence of neutralizing antibodies against IL-1 alpha, IL-1 beta, IL-6 and IL-8; considerable PBL attractant activity was noted in the pre-irradiation SBF from both patient groups; a finding consistent with previous reports of such activity in samples from normal skin, and at least in CAD patients, a proportion of this activity appeared to be due to IL-1, pre-incubation of SBF with neutralizing antibodies against IL-1 alpha and IL-1 beta reducing the effect significantly. Substantial PBL attractant activity was present also in the SBF from 1-3 h and 24 h post-irradiation samples in both patient groups and again, IL-1 neutralizing antibodies reduced this in the 1-3 h and 24 h CAD samples. In addition, neutralizing antibodies against IL-6 and IL-8 reduced the activity in the 24 h PLE samples significantly and although not fully conclusive in the case of IL-1, these data suggest that IL-6, IL-8 and possibly IL-1 may be involved in the induction of PBL infiltrates, and perhaps other events, in both PLE and CAD.
Clin Exp Dermatol 1999 Jul
PMID:The role of interleukins 1, 6 and 8 as lymphocyte attractants in the photodermatoses polymorphic light eruption and chronic actinic dermatitis. 1045 40


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