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)

Normal human epidermal keratinocytes (NHEK) and dermal fibroblasts express a cell-specific pattern of efflux transport proteins. Since regulatory mechanisms for these transporters in cells of the human skin were unknown, we analyzed the influence of inflammatory cytokines on the expression of multidrug resistance-associated proteins (MRP1, 3, 4, 5). Using real-time PCR, RT-PCR, cDNA microarray, immunostaining and efflux assays we demonstrated that stimulation of NHEK and primary human dermal fibroblasts with interleukin-6 (IL-6), in combination with its soluble alpha-receptor, or oncostatin M (OSM) for 24-72 h resulted in an upregulation of MRP expression and activity. Both cytokines induced a strong activation of signal transducer and activator of transcription (STAT)1 and STAT3 as well as the mitogen-activated protein kinase (MAPK) Erk1/2. OSM additionally activated proteinkinase B strongly. Using the MAPK/extracellular signal-regulated kinase kinase 1-specific inhibitor U0126 we could exclude a stimulatory effect of MAPK on MRP gene expression. Inhibition of the phosphatidylinositol 3-kinase, however, indicated that this pathway might be involved of OSM-mediated upregulation of MRP4 in dermal fibroblasts. Several inflammatory skin diseases show an enhanced expression of IL-6-type cytokines. Correspondingly, upregulation of MRP expression was found in lesional skin taken from patients with psoriasis and lichen planus.
J Invest Dermatol 2005 Jan
PMID:Interleukin-6-type cytokines upregulate expression of multidrug resistance-associated proteins in NHEK and dermal fibroblasts. 1565 50

Primary cutaneous plasmacytoma is a rare type of cutaneous B-cell lymphoma, characterized by clonal proliferation of plasma cells, that primarily develops in the skin. Five cases have been described to date in which a local triggering stimulus may be involved in development of this skin tumour. We describe the case of a primary cutaneous plasmacytoma localized to the lower lip. This site had been affected for 15 years with recurrent herpes simplex virus-1 infection. Neoplastic plasma cells were found to be bcl-2-positive. We hypothesize that chronic stimulation of keratinocytes by herpes simplex virus-1, possibly through toll-like receptors, may have favoured the release of cytokines (e.g. interleukin-6) able to induce plasma cell proliferation, transformation and survival.
Clin Exp Dermatol 2005 May
PMID:Primary cutaneous plasmacytoma: a role for a triggering stimulus? 1580 75

The role of human papillomaviruses (HPVs) in the pathogenesis of psoriasis is uncertain, and it has been postulated that the virus can act as a putative superantigen or it is activated from a latent status by inflammatory cytokines. To determine the involvement of HPV in the pathogenesis of psoriasis, primary cultures of keratinocytes from psoriatic lesions were analysed for the viral presence and for the production of inflammatory cytokines. Biopsies were taken from psoriatic lesions of 11 patients and from healthy donors undergoing plastic surgery. HPV DNA/RNAs were detected by nested polymerase chain reaction methods. The secretion of interleukin-6 (IL-6), IL-8 and IL-18 was determined in the conditioned medium by commercial enzyme-linked immunosorbent assay kits. Sixty-four per cent of the psoriatic keratinocytes were positive to HPV type 5 (HPV5), whereas no normal samples showed the presence of viral sequences. In the corresponding paraffin-embedded sections, multiple infection by HPV5 and HPV1 was detected. Comparable results in the production of inflammatory cytokines were obtained from HPV-infected vs. non-infected cell cultures. Specific HPV5 mRNAs were detected in the keratinocytes in the absence of cytokine stimulation, indicating that the expression of the viral genome may not be a consequence of the activation of the viral promoter by cytokines. The results are suggestive of an involvement of HPV5 in the psoriasis and reinforce the hypothesis that the replication of this virus in the psoriatic keratinocytes may cause the epidermal hyperproliferation as well as the antigen stimulation, which induces autoimmune phenomena.
Exp Dermatol 2005 Nov
PMID:Human papillomavirus type 5 in primary keratinocytes from psoriatic skin. 1623 4

We report a 75-year-old Japanese woman with classic Kaposi's sarcoma. PCR amplified human herpesvirus 8 (HHV-8) DNA sequences from her skin lesions and peripheral blood mononuclear cells (PBMC), but not her plasma, saliva or urine. An antibody test against HHV-8 lytic antigens was positive. Immunohistochemical staining detected latent antigen. There was no evidence of HHV-8 infection in her husband, sister or daughter. Genes coding for HHV-8-encoded viral interleukin-6, viral macrophage inflammatory protein I, viral G protein-coupled receptor, viral cyclin D and viral Bcl-2 were expressed to the same degree in both her skin lesion and PBMC. Latency-associated T0.7 mRNA and HHV-8-encoded viral tegument protein genes were expressed in her PBMC at levels lower than in the skin lesions. Based on the gene expression profile, we concluded that lytic HHV-8 infection was present in her skin lesions and PBMC.
Clin Exp Dermatol 2006 Jan
PMID:Transcripts of the human herpesvirus 8 genome in skin lesions and peripheral blood mononuclear cells of a patient with classic Kaposi's sarcoma. 1630 2

The cellular and cytokine dynamics of reactions triggered by atopy patch testing with house dust mites were studied in six high-IgE beagles. Sites were scored and biopsied at 6, 24, 48, and 96 h, and samples were processed for histopathology, immunohistochemistry, and polymerase chain reaction (PCR). All dogs developed positive reactions at some point in time. Mean clinical scores were significantly higher than baseline at 24, 48, and 96 h. Clinically, one of six dogs had a positive reaction at 6 h; two of six reacted at 24 and 48 h, and five of six at 96 h. Histologically, superficial perivascular mononuclear and granulocytic dermatitis developed (5/6) after 6 h, and progressed in severity at 24 h (6/6). Additionally, at 48 h epidermal spongiosis, hyperplasia and pustules developed (5/6), and were marked at 96 h (6/6). At and beyond 6 h, progressive CD1c-positive epidermal Langerhans cell hyperplasia with cluster formation and dermal dendritic cell infiltration was noted. Cutaneous infiltration of CD3-positive T lymphocytes with epidermal clusters developed over time. mRNA expression for the cytokines gamma-interferon (gamma-IFN), interleukin-6 (IL-6), IL-12p35, IL-13, IL-18, and thymus and activation regulated chemokine (TARC) exhibited significant increases during the challenge compared to baseline, but there was no appreciable alteration in expression for tumour necrosis factor-alpha (TNF-alpha), IL-12p40, IL-10, regulated on activation normal T-cell expressed and secreted (RANTES), IL-5, IL-2, IL-4, and IL-8. No correlation was detected between clinical scores and cytokines. It is concluded that IL-6 plays a role in early reactions followed by an increase of TARC and IL-13, while IL-18 progressively increases in later reactions.
Vet Dermatol 2006 Apr
PMID:Cellular and cytokine kinetics after epicutaneous allergen challenge (atopy patch testing) with house dust mites in high-IgE beagles. 1651 53

There is evidence that cytokines (CKs) play a significant role in the development and/or progression of skin cancer. The aim of the present study was to investigate the mRNA expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8 in biopsy specimens of basal cell carcinoma (BCC), and to compare the results with the mRNA levels of non-lesional skin of BCC patients and healthy subjects. Skin samples were obtained from 22 patients with BCC (lesional, non-lesional) and 25 healthy subjects (controls). Routine histology and real-time RT-PCR was performed. Histological examination revealed 12 nodular BCCs and 10 superficial BCCs. The mRNA levels of CKs observed in healthy controls did not significantly (P > 0.05) differ from non-lesional CK levels of BCCs patients. However, IL-6 and IL-8 levels of lesional skin were significantly (P < 0.05) higher than the CK levels observed in non-lesional skin and controls, respectively. mRNA expression of IL-6 and IL-8 showed a significant positive correlation (r = 0.51; P < 0.05). There was no significant (P > 0.05) difference between lesional mRNA levels of TNF-alpha and those levels observed in non-lesional skin and controls. The mRNA expression of CKs found in nodular and superficial BCCs did not significantly differ (P > 0.05). BCC is associated with a significant increase of IL-6 and IL-8 expression. We have shown for the first time that upregulation of IL-6 mRNA significantly correlates with IL-8 overexpresssion. In accordance with previous studies our data suggest a role for IL-6 and IL-8 in the development and/or progression of BCC, since mRNA expression of both CKs are significantly increased in tumour tissue.
Arch Dermatol Res 2006 Aug
PMID:Cytokine mRNA expression in basal cell carcinoma. 1682 14

Several clinical reports have shown promising, but not optimal, results from photodynamic therapy with delta-aminolevulinic acid-derived protoporphyrin IX, termed ALA-PDT, as a treatment for cutaneous leishmaniasis (CL). Therefore, understanding the basis of the phototoxic response of Leishmania parasites to ALA-PDT may be critical for optimization. We report here both in vitro and in vivo mechanistic studies of ALA-PDT against CL. Following in vitro co-incubation of Leishmania major with 0.1 microM ALA, the PpIX concentration remained at the basal level, whereas after co-incubation with 0.1 microM exogenous PpIX, the PpIX level was 100-fold higher. No differences in ALA-derived PpIX levels were detected between Leishmania-infected and non-infected J774.2 cells, and PDT did not demonstrate any parasiticidal effects on amastigotes. In contrast, in vivo topical ALA-PDT, performed on a murine CL model, resulted in significant reductions of the parasite loads and vigorous tissue destruction. After ALA-PDT, a dramatically decreased percentage of macrophages and increased levels of interleukin-6 were observed in the infected skin. The clinical outcome observed with ALA-PDT is likely the result of unspecific tissue destruction accompanied by depopulation of macrophages rather than direct killing of parasites.
Exp Dermatol 2007 Aug
PMID:Parasiticidal effect of delta-aminolevulinic acid-based photodynamic therapy for cutaneous leishmaniasis is indirect and mediated through the killing of the host cells. 1762 92

This study reports three cases of an unusual leprotic reaction characterized by superficial bullous ulcerative cutaneous lesions associated with high fever, malaise and oedema in patients with leprosy. Two patients responded to thalidomide treatment, with regression of the symptoms and skin ulcers. The third patient responded to thalidomide plus prednisone. Analysis of the ulcerated skin lesions showed dermal oedema with mononuclear cell infiltrate enriched for gammadelta-positive T lymphocytes and an increased number of Mycobaterium leprae bacilli within capillary endothelium. In contrast, gammadelta+ cells were decreased in or absent from the blood. Tumour necrosis factor-alpha and interleukin-6 were raised in the serum of the patients at the onset of the reaction. After the episode, cytokine levels and the percentage of gammadelta+ cells in the blood returned to normal. These cases characterize an uncommon leprotic reaction with clinical similarities to type II reaction and may indicate a significant role for gammadelta+ T cells in its pathogenesis.
Clin Exp Dermatol 2008 May
PMID:Clinical, immunological and histological aspects of an uncommon type II reaction in patients with lepromatous leprosy. 1826 Nov 42

It is unclear whether any clinical and laboratory features are associated with pulmonary fibrosis (PF) in systemic sclerosis (SSc). We assessed these features using a database of 29 patients with SSc and anti-topoisomerase I antibodies and 68 patients with SSc and anticentromere antibody (ACA). Clinical features were not associated with the incidence of PF in patients with SSc and anti-topoisomerase I antibodies, although severe skin sclerosis was correlated with the presence of PF in patients with ACA. Serum IgG levels were often raised in patients with SSc and PF. Serum IgG levels in patients with PF were significantly higher than those in patients without PF, and were negatively correlated with percentage vital capacity and percentage diffusing capacity of the lung for carbon monoxide. In addition, serum IgG levels were correlated with serum interleukin-6. Thus, serum IgG levels are associated with PF in patients with SSc and anti-topoisomerase I antibodies and in patients with SSc and ACA.
Clin Exp Dermatol 2008 May
PMID:Elevation of IgG levels is a serological indicator for pulmonary fibrosis in systemic sclerosis with anti-topoisomerase I antibodies and those with anticentromere antibody. 1831 58

Acne is a complex, chronic and common skin disorder of pilosebaceous units. Although it is known that exacerbation of acne results from emotional stress, the nature of the association between stress and acne remains unclear. This is due in part to the lack of substantial evidence regarding the participation of cutaneous neurogenic factors in the pathogenesis of acne. Culture of sebocytes provides a new insight into the participation of neuropeptides, notably substance P (SP), in the pathophysiology of acne. To examine the possible involvement of neurogenic factors in the pathogenesis of acne, we used immunohistochemistry and RT-PCR to compare the expression of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), peroxisome proliferators activated receptors-gamma (PPAR-gamma) on the cultured sebocytes stimulated by SP. IL-1 is primarily proinflammatory cytokines to stimulate the expression of genes associated with inflammation. IL-6 is a pleiotropic cytokine with a wide range of biological activities and regulates inflammation. TNF-alpha is a pleiotropic pro-inflammatory cytokine that exerts multiple biologic effects. PPAR-gamma is a nuclear hormone receptor and plays a unique role in stimulating sebocyte lipogenesis. More numerous immunoreactivity to IL-1, IL-6, TNF-alpha and PPAR-gamma and increased RNA amplification for IL-1, IL-6, TNF-alpha and PPAR-gamma were observed after addition of SP compared with the control. This study reveals that SP is involved in the pathogenesis of acne.
Arch Dermatol Res 2008 Jul
PMID:Influence of substance-P on cultured sebocytes. 1842 22


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