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

Involvement of T-lymphocytes in the pathogenesis of psoriasis and atopic dermatitis is well established. The question arises as to whether not only tissue infiltrating but also circulating T-lymphocytes are involved in the disease process. Therefore we sought to determine whether T-lymphocytes from patients with psoriasis and atopic dermatitis show abnormal biological behavior to the proinflammatory chemokine interleukin 8 (IL-8) in vitro as studied by their chemotactic activity. In addition, the expression of T-cell activation markers such as HLA-DR and interleukin 2 receptor (IL-2R) were analysed with FACS-technique. In all, 25 patients with psoriasis (13 patients with severe psoriasis and 12 patients with mild psoriasis) and 11 patients with atopic dermatitis were investigated. For comparison. T-lymphocytes from 14 healthy controls were tested equally. The results show that T-cell chemotactic responses to IL-8 were significantly decreased in patients with severe psoriasis as compared to healthy controls. T-cells from patients with atopic dermatitis demonstrated an even more pronounced decrease in chemotactic response as compared to T-cells from psoriasis patients or healthy controls. In contrast, increased expression of activation markers HLA-DR and IL-2R were demonstrated in circulating T-cells from patients with severe psoriasis and atopic dermatitis in comparison to healthy controls. It can be concluded that circulating T-cells in patients with severe psoriasis and atopic dermatitis show a decreased in vitro chemotactic response to IL-8. Furthermore, the in vivo phenotypic activation state of T-lymphocytes in these patients seemed to be associated with their decreased in vitro functional capacity.
Exp Dermatol 1996 Dec
PMID:The chemotactic activity of T-lymphocytes in response to interleukin 8 is significantly decreased in patients with psoriasis and atopic dermatitis. 902 95

Activation of endothelium is a critical event during the initiation of inflammatory processes and is associated with the induction of cell adhesion molecules and cytokines. The latter include chemotactically active cytokines (chemokines) that promote leukocyte diapedesis from the circulation to sites of evolving inflammation. In this study we evaluated the chemokine repertoire of human endothelial cells derived from the skin (HDMECs) and regulation of these chemokines by cytokines. HDMECs and an immortalized human dermal microvascular endothelial cell line, HMEC-1, were investigated for the expression of C-X-C and C-C chemokines at mRNA and protein levels. Upon stimulation with interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), both HDMECs and HMEC-1 expressed high levels of IL-8, GRO, and monocyte chemoattractant protein-1 (MCP-1). RANTES was only weakly induced; however, concomitant treatment with TNF-alpha and interferon-gamma (IFN-gamma) led to upregulation of RANTES, indicating a synergy between these two cytokines. The C-X-C chemokine IFN-inducible protein-10 was upregulated by IFN-gamma but not by other cytokines studied. Macrophage inflammatory protein-1alpha and beta, 1-309, and ENA-78 could not be induced. The chemokine repertoires of HDMECs and HMEC-1 were compared to those of human umbilical vein endothelium and found to be rather similar with the important exception that IFN-gamma and IL-4 up-regulated MCP-1 only in macrovascular endothelium. Our data indicate that HDMECs contribute to the dermal cytokine network by selective production of MCP-1, IL-8, GRO, RANTES, and IP-10, which may critically influence the site-specific recruitment of leukocyte subsets.
J Invest Dermatol 1997 Apr
PMID:The chemokine repertoire of human dermal microvascular endothelial cells and its regulation by inflammatory cytokines. 907 72

The purpose of this study was to clarify the relationship between the cellular and humoral immune components in the pathogenesis of vitiligo vulgaris. By using cytokines as indicators of peripheral mononuclear cell (MNC) function, we compared the effects of phytohemagglutinin (PHA) and purified IgG on MNCs derived from patients suffering from active vitiligo with those from normal controls. The results revealed (i) a significant increase in spontaneous production of IL-6 and IL-8 in patients; (ii) PHA, purified IgG from patients (IgG-anti-MC), or IgG from normal controls (N-IgG) induced a significant increase in IL-6 but diminished GM-CSF, TNF-alpha, and IFN-gamma release in patients; and (iii) IgG-anti-MC brought about a significantly higher stimulatory effect on IL-1beta and IFN-gamma production than N-IgG in normal controls. Immunologically, IL-6 can enhance melanocyte ICAM-1 expression, which may increase leukocyte-melanocyte attachment and cause melanocyte damage in vitiligo. A decrease in GM-CSF (an intrinsic growth factor for melanocyte) production may retard recovery from vitiligo by checking the proliferation of surviving melanocytes. A significant decrease in TNF-alpha and IFN-gamma production may partially explain the reduced inflammatory reaction in vitiliginous lesions. That IgG-anti-MC stimulates an increase in IL-1beta and IFN-gamma production in controls suggests that IgG-anti-MC may play a role in melanocyte destruction mediated by monocytes.
J Invest Dermatol 1997 Apr
PMID:Alterations in IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma release by peripheral mononuclear cells in patients with active vitiligo. 907 86

The in vivo response to ultraviolet B (UVB) radiation in skin is characterized by the accumulation of both mononuclear and polymorphonuclear cells within the dermis and an induction of vascular endothelial adhesion molecules. Epidermal production of cytokines (IL-8 and TNF-alpha) has been strongly implicated in the development of UVB-induced inflammation. In the current study, we examined the time course of IL-8 and TNF-alpha mRNA and protein expression in the epidermis over a 24-h period after in vivo UVB irradiation. Also, the induction of adhesion molecule expression and the accumulation of neutrophils within the dermis were followed. We found constitutive expression of both cytokines (mRNA and protein) in the epidermis of unirradiated skin. IL-8 was rapidly upregulated after irradiation and mRNA and protein increased at 4 h, reaching a maximum between 8 and 24 h. TNF-alpha mRNA and protein was minimally increased by 8 h after UVB irradiation and reached a maximum by 24 h. No significant alteration in ICAM-1 or VCAM-1 expression was observed. E-selectin expression, which was absent from control samples, was increased from 4 h onward and also reached a maximum at 24 h, coinciding with peak neutrophil accumulation. A strong correlation (r = 0.96) was found between number of E-selectin-positive vessels and numbers of infiltrating neutrophils at this time. Moreover, because E-selectin expression was increased before any apparent increase in TNF-alpha protein (4 h), TNF-alpha does not appear to be involved in the early induction of the adhesion molecule, but cytokines such as TNF-alpha and IL-8 may act subsequently to augment the inflammatory response.
J Invest Dermatol 1997 May
PMID:TNF-alpha and IL-8 are upregulated in the epidermis of normal human skin after UVB exposure: correlation with neutrophil accumulation and E-selectin expression. 912 30

To investigate the role of prostaglandin (PG) E1 in preventing scar formation as well as that of the related cytokines, we culture fibroblasts from hypertrophic scar tissue (SDF) and normal dermis (NDF) collected from patients with scar contracture. We have compared the type I collagen synthesis, type I collagenase activity, and the production of interleukin (IL)-6, IL-8 and transforming growth factor (TGF)-beta(1) in two types of cultured fibroblasts before and after addition of PGE1. Our results demonstrated that levels of type I collagen and TGF-beta(1) production were higher and that type I collagenase activity and IL-8 production were significantly lower in the culture supernatants of SDF. There was no significance difference in IL-6 production between SDF and NDF culture supernatants. On the other hand, PGE1 significantly increased type I collagenase activity and IL-8 production in the SDF culture supernatants and it increased IL-6 and TGF-beta(1) production in both types of fibroblasts. However, there was no effect on synthesis of type I collagen in either group. To further investigate the role of TGF-beta(1) in NDF and SDF, exogenous recombinant human (rh) TGF-beta(1) was added. In NDF group, rhTGF-beta(1) induced a decrease in the type I collagenase/type I collagen ratio, while rhTGF-beta(1) had no effect on the same ratio in the SDF group. These results suggest that PGE1 may have a role in the prevention of hypertrophic scar by increasing the activity of type I collagenase.
J Dermatol Sci 1997 Mar
PMID:Effects of prostaglandin E1 on cultured dermal fibroblasts from normal and hypertrophic scarred skin. 913 79

Anthralin is a most widely used compound for topical treatment of psoriasis. Whereas numerous studies have ascertained anthralin as a safe and effective drug its mode of action still remains unclear. Previous studies demonstrated dose-dependent inhibition of a number of pro-inflammatory functions in human neutrophils and monocytes (MO). The aim of the present study was to investigate in stimulated MO the effect of anthralin on the secretion of cytokines which are of known importance for the psoriatic tissue reaction. Highly purified MO were incubated with anthralin (0.01-1.0 microgram/ml), its clinically inactive derivative danthrone (0.1 and 10 micrograms/ml), the solvent acetone, or medium alone. Culture supernatants were analysed for immunoreactivity for interleukin-1 beta, and -8 (IL-1 beta, IL-8), and tumour necrosis factor alpha (TNF-alpha) by specific ELISA. IL-6 bioactivity was determined using the B9-bioassay. Additionally, IL-1 bioactivity was measured by the D10[N4]M-bioassay. The results show a dose-dependent inhibition of MO IL-6, IL-8, and TNF-alpha release with a half-maximal inhibitory concentration of 0.25-0.6 microgram/ml of anthralin. There was no effect of danthrone or acetone on the secretion of these cytokines from MO. Secretion of IL-1 beta immunoreactivity measured by ELISA as well as determination of biological activity of IL-1 using the D10[N4]M-bioassay revealed a slight increase in IL-1 secretion with a maximum at an anthralin concentration of 0.1 microgram/ml. Danthrone at a concentration of 10 micrograms/ml and acetone (0.1%) similarly enhanced IL-1 secretion from human MO measured by both methods. Our results demonstrate a differential, dose-dependent inhibition of cytokine secretion from human MO by anthralin. The present data provide evidence that the anti-inflammatory and anti-proliferative activity of anthralin may at least in part be due to its inhibitory effect on pro-inflammatory cytokine secretion by MO.
Br J Dermatol 1997 Apr
PMID:Anthralin (dithranol) in vitro inhibits human monocytes to secrete IL-6, IL-8 and TNF-alpha, but not IL-1. 915 55

Spontaneous tumor regression, which is observed clinically and histologically in some primary melanomas, occurs in the absence of any effective therapy. It is probably immunologically mediated, because regressing melanomas are infiltrated with larger numbers of activated T cells, primarily CD4+, than nonregressing melanomas. To investigate the hypothesis that spontaneous regression of melanomas is caused by T-cell cytokine production, cytokine mRNA expression in 20 primary melanomas was examined using a noncompetitive, quantitative reverse-transcriptase polymerase chain reaction method. DNA standards were used to generate known numbers of molecules in each sample. Results were standardized to the internal control, glyceraldehyde-3-phosphate dehydrogenase. mRNA for CD35, lymphotoxin (TNF-beta), and IL-2 were significantly elevated in the ten regressing melanomas compared to the ten nonregressing melanomas. IFN-gamma mRNA was also elevated in regressing melanomas but failed to reach statistical significance. The Th2 cytokines IL-10 and IL-13 did not show differences in the regressing melanomas compared to nonregressing melanomas; neither did the pro-inflammatory cytokines IL-1alpha, IL-1beta, IL-6, IL-8, and TNF-alpha, nor the growth factors, bFGF and TGF-beta or GM-CSF. This study shows an association between Th1 cytokines and spontaneously regressing melanomas. Although we have not shown that these cytokines cause regression, these findings support our hypothesis that activated CD4+ T cells may mediate melanoma regression by secretion of Th1 cytokines.
J Invest Dermatol 1997 Jun
PMID:T helper 1 cytokine mRNA is increased in spontaneously regressing primary melanomas. 918 21

Increased levels of several cytokines, mainly proinflammatory mediators, have been reported in psoriatic lesions. Little information, if any, is available concerning other cytokines, especially those initially studied as marrow differentiation agents. Using the experimental approach of measuring cytokines released by skin organ cultures. IL-11 and three other proinflammatory cytokines (IL-1 beta, IL-6 and IL-8) were determined using commercially available ELISA kits in supernatants of ten biopsies from lesional and nonlesional psoriatic skin areas and in supernatants of biopsies from ten normal volunteers. The results obtained showed that the amounts of IL-11 and the other three modulators were significantly increased in the material from the lesional areas (P < 0.01). The amounts of IL-11, which is known to have functional activity similar to the proinflammatory cytokines and to share a receptor component with IL-6, were also correlated with the disease severity index (R = 0.69, P = 0.04). In addition, a nearly significant correlation was noted between the amounts of IL-11 released by the lesional and the nonlesional skin biopsies (R = 0.66, P = 0.05). More detailed studies are needed to clarify whether IL-11 plays a specific functional role in psoriasis, but this study emphasizes the complexity of the pathogenesis of psoriasis and the cytokine network, including activation of proinflammatory and haemopoietic biological response modifiers, in this disease.
Arch Dermatol Res 1997 Jun
PMID:Interleukin-11 production is increased in organ cultures of lesional skin of patients with active plaque-type psoriasis as compared with nonlesional and normal skin. Similarity to interleukin-1 beta, interleukin-6 and interleukin-8. 924 18

The expression of IL-8 in psoriasis has been clearly shown with the use of immunocytochemical, RT-PCR and in situ hybridization methods. The presence of its ligand, the IL-8 receptor, has been demonstrated by the RT-PCR technique. We report here a study of the expression of both IL-8 type A and B receptors by immunohistochemical techniques, using one polyclonal and four monoclonal antibodies. By this technique, we found that the neutrophilic granulocytes express the IL-8 type A receptor, whereas the IL-8 type B receptor was present on the keratinocytes. The type B receptor on the keratinocytes was localized in the suprabasal layers of the epidermis. Following therapy, the expression of the IL-8 type B receptor on the keratinocytes was reduced. This could suggest that IL-8 in psoriasis is involved in the disturbed differentiation rather than in proliferation, probably via an autocrine loop.
Arch Dermatol Res 1997 Jul
PMID:The expression of interleukin-8 receptor in untreated and treated psoriasis. 926 20

Pentoxifylline (PTX) is a methylxanthine derivative used in a wide range of dermatoses. As well as its hemorrheologic activity, PTX has anti-inflammatory properties. Buflomedil chlorhydrate (BC) is another hemorrheological drug with peripheral vasodilatory action, whose clinical uses are similar to those of PTX. Both drugs increase intracellular levels of cAMP, either secondary to phosphodiesterase inhibition (PTX) or adenyl-cyclase stimulation (BC). Long-term cultures of normal human keratinocytes were prepared in a free-serum medium, and stimulated with 1 mg/ml of phorbol 12-myristate 13-acetate (TPA) and PTX or BC (100-1000 micrograms/ml). Levels of TNF-alpha, IL-1 alpha, IL-1 beta, IL-8 and TGF-beta 1 using ELISA and Northern blot or RT-PCR techniques were measured. TPA-induced TNF-alpha and IL-8 release from keratinocytes. TPA did not induce IL-1 alpha or IL-1 beta release of keratinocytes. TPA increased RNA expression of the TNF-alpha, IL-1 alpha, IL-1 beta, IL-8 and TGF-beta 1. BC diminished TPA-induced TNF-alpha and IL-8 release from keratinocytes; in the case of IL-8 it is possible that this inhibition occur to transcriptional level. Moreover PTX was unable to inhibit TNF-alpha and IL-8 synthesis and expression. PTX and BC reduced TPA-induced IL-1 alpha and beta expression. It is possible that BC action is specifically exerted on keratinocytes, because we did not find similar results with TNF-alpha and IL-8 synthesis in mononuclear peripheral blood cells.
Exp Dermatol 1997 Aug
PMID:Differential modulation of IL-8 and TNF-alpha expression in human keratinocytes by buflomedil chlorhydrate and pentoxifylline. 929 91


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