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)

Previous studies have shown that neutrophil-activating peptide 1/interleukin-8 (IL-8) is present in psoriatic scales and to a lesser extent in normal human epidermis. A panel of monoclonal antibodies and polyclonal antisera raised against IL-8 was used to localize IL-8 with immunoperoxidase techniques in non-lesional and lesional skin of patients with psoriasis and palmo-plantar pustulosis (PPP), and in corresponding sites from healthy subjects. Intracellular IL-8 immunoreactivity was found in all epidermal cell layers in biopsies of healthy subjects and in non-lesional and lesional skin in both PPP and psoriasis. The most intense immunolabeling was regularly found in the basal cell layer. Intercellular epidermal IL-8 immunolabeling was regularly detected in lesional biopsies in PPP and psoriasis, but not in healthy subjects or non-lesional skin in PPP and psoriasis. No intercellular immunolabeling was detected after successful treatment of lesional skin. The majority of cells along the eccrine sweat glands, dermal mononuclear cell infiltrates, and endothelial cells were IL-8 immunoreactive in all biopsies studied. The present study suggests that IL-8, its precursor form, or, alternatively, a degradation product is present in normal human epidermis.
J Invest Dermatol 1992 Jan
PMID:Interleukin-8 immunoreactivity in the skin of healthy subjects and patients with palmoplantar pustulosis and psoriasis. 172 43

Neutrophil accumulation in the epidermis is a histologic characteristic of psoriasis. We addressed the question: What is the major protein-like chemotactic principle responsible for neutrophil accumulation? Purification of proteinaceous neutrophil chemoattractants from extracts obtained from psoriatic scales by multistep high-performance liquid chromatography (HPLC) yielded three biochemically distinct polypeptides with potent neutrophil chemotactic activity. Aminoterminal amino acid sequence analysis of the quantitatively major neutrophil attractant revealed the sequence ELRXQXIKTYSK, which is identical to that of a 69 residue form of neutrophil-activating peptide-1/interleukin 8 (NAP-1/IL-8). The second major attractant showed the sequence XXVATELRXQXL . . ., which is identical to that of the gene product of the oncogene "gro" as well as "melanoma growth stimulatory activity, MGSA," whereas the third and minor neutrophil chemotaxin has an NH2-terminal sequence identical with NAP-1/IL-8. Estimation of NAP-1/IL-8-related proteins and gro/MGSA by HPLC combined with bioassay revealed a mean of 3.3 +/- 1.7 ng NAP-1/IL-8-related proteins (n = 11) and 3.2 +/- 1.9 ng gro/MGSA (n = 11) per 1 mg psoriatic scales. In normal heel callus (n = 8), these neutrophil attractants were found at concentrations below 0.02 +/- 0.01 ng/mg. The finding of more than 150-times increased amounts of both NAP-1/IL-8 and gro/MGSA in lesional psoriasis material suggest that these mitogenic as well as neutrophil- and lymphocyte-chemotactic compounds may play an important role in the pathogenesis of psoriasis.
J Invest Dermatol 1992 Feb
PMID:Neutrophil-activating proteins in psoriasis. 173 89

Interleukin-8 (IL-8), formerly known as NAP-1, is formed by a variety of cells upon stimulation with IL-1 or tumor necrosis factor (TNF). The biologic activity of the cytokine involves activation of almost every neutrophil function studied so far in different species. In the present study, we compared the effects of recombinant human IL-8 (rIL-8) and the lipid mediators, leukotriene B4 (LTB4) and platelet-activating factor (PAF), on neutrophil functions in dogs. All three chemotactic factors induced neutrophil aggregation and chemotaxis, with rIL-8 being far more potent than LTB4 and PAF. The migration induced by rIL-8 was significantly greater than that observed towards LTB4 and PAF. In the aggregation assay, rIL-8 was shown for the first time to be a potent stimulant. The aggregation response was more persistent than that obtained with LTB4 and PAF and the potency of rIL-8 was greater. An intradermal dose-response study showed that rIL-8 is an extremely potent inducer of selective neutrophil infiltration in canine skin. The infiltration was more pronounced than following injection of LTB4 or PAF. It was proposed that the superior effect of rIL-8 was caused by a synergistic effect between injected rIL-8 and LTB4, which was shown to be produced in biologically active amounts by canine neutrophils stimulated with rIL-8. From a therapeutic point of view, the simultaneous presence of rIL-8 and LTB4 in inflammatory skin diseases highlights the need to develop drugs that inhibit the production and/or effect of both mediators.
J Invest Dermatol 1991 Feb
PMID:Recombinant human interleukin-8 is a potent activator of canine neutrophil aggregation, migration, and leukotriene B4 biosynthesis. 184 1

The presence of the leukocyte chemotactic cytokine interleukin 8 (IL-8) in psoriatic scales and in epidermal tissue overlying allergic patch test reactions suggests a role for this cytokine in certain inflammatory skin diseases. IL-8 can be produced by several cell types present in the skin. Their relative potentials for IL-8 expression has, however, not yet been studied, due to the lack of convenient methods for quantitative comparison of specific mRNA amounts in different cell types. Using a new method for quantification, we compared specific IL-8 mRNA amounts in cultures of keratinocytes, dermal fibroblasts, endothelial cells, and monocytes, stimulated with interleukin 1 alpha (IL-1 alpha). Endothelial cells produced very high, fibroblasts and monocytes intermediate, and keratinocytes low amounts of IL-8 mRNA. We also studied the time course of IL-8 mRNA levels in the four cell types following IL-1 alpha stimulation, and found a clear difference both in onset and stability of the response. We discuss the different strength of the response at different time points in the cell types analyzed in relation to their possible role in regulation of the normal response to stimulation.
J Invest Dermatol 1991 Sep
PMID:Quantitative determination of IL-1 alpha-induced IL-8 mRNA levels in cultured human keratinocytes, dermal fibroblasts, endothelial cells, and monocytes. 187 50

The capacity of human melanocytes and melanoma cells to produce IL-8 and monocyte chemotactic and activating factor (MCAF) was investigated. Melanocytes expressed mRNA for IL-8 and MCAF, when stimulated with either IL-1 alpha or TNF alpha, but not when stimulated with IL-6, IFN gamma, or LPS alone. IL-8 and MCAF could be induced in a dose-dependent fashion with doses as low as 0.1 ng/ml TNF alpha and 0.5 ng/ml IL-1 alpha. IL-8 and MCAF mRNA were rapidly expressed and peaked between 2 and 4 h for IL-8 and between 4 and 8 h for MCAF. This correlated well with the accumulation of IL-8 antigen as measured by a radioimmunoassay. Supernatants from melanocyte cultures stimulated with either IL-1 alpha or TNF alpha and separated on a heparin-Sepharose column became positive for neutrophil and monocyte chemotactic activity in a dose- and time-dependent fashion. When IFN gamma was added to melanocyte cultures stimulated with suboptimal doses of TNF alpha there was a synergistic increase in secreted IL-8 protein and monocyte chemotactic activity. These data provide further evidence for the possible role of melanocytes in the initiation of an inflammatory reaction. Three different malignant melanoma cell lines stimulated with either TNF alpha or IL-1 alpha expressed IL-8 mRNA, but not mRNA for MCAF. The IL-8 mRNA signal corresponded well with the amount of secreted IL-8 protein. These data suggest that IL-8 and MCAF may play a role in growth regulation and spreading of melanomas.
J Invest Dermatol 1991 Sep
PMID:Expression and secretion of leukocyte chemotactic cytokines by normal human melanocytes and melanoma cells. 187 58

Previous studies have suggested that epidermal-derived interleukin-1 is involved in the pathogenesis of cutaneous T-cell lymphoma (CTCL); however, the findings are conflicting and studies that combine immunohistochemistry and functional activity have not been performed. We investigated the interleukin-1 level in epidermis of patients with cutaneous T-cell lymphoma using both immunohistochemistry, enzyme-linked immunosorbent assays, and the thymocyte co-stimulation assay. Using supernatants obtained from epidermal cell cultures, we found a significant but small increase of interleukin 1 alpha protein release from involved CTCL epidermis compared to normal epidermis from healthy individuals. Both keratinocytes and leukocytes could release interleukin-1 alpha, but the majority was derived from the keratinocytes. Interleukin-1 beta protein was not detectable. In the thymocyte assay, interleukin-1 alpha was found to be biologically active. When lymphokines derived from a T-cell clone obtained from involved CTCL skin were co-cultured with epidermal cells, an enhanced release of epidermal interleukin-1 alpha could be demonstrated. Because interleukin 1 alpha was increased, we investigated the presence of interleukin 1-inducible keratinocyte-derived interleukin 8 and found it increased in CTCL epidermis compared to normal epidermis from healthy individuals. This study demonstrated an elevated epidermal IL-1 alpha level and IL-8 immunoreactivity in CTCL epidermis, which suggests that this elevated level is induced by lymphokines released from activated T cells.
J Invest Dermatol 1991 Nov
PMID:Epidermal interleukin 1 alpha functional activity and interleukin 8 immunoreactivity are increased in patients with cutaneous T-cell lymphoma. 140 10

Neutrophil-activating protein-1/interleukin 8 (NAP-1/IL-8), purified to homogeneity from lipopolysaccharide-stimulated human peripheral blood monocytes, was injected intracutaneously into human skin. Sequential biopsy specimens were taken in order to investigate the sequence of ultrastructural changes induced by the cytokine. Whereas intracutaneous injection of 100 ng of NAP-1/IL-8 per site caused no macroscopic changes, by histology infiltration with polymorphonuclear leukocytes (PMN) and monocytes was present within 1 h and increased at 3 and 5 h. No lymphocyte infiltration was noted. The first ultrastructural changes (30 min) consisted of the presence of cytoplasmic 7-nm microfilament bundles, as well as numerous protrusions of the luminal plasma membrane of endothelial cells (EC). As a striking feature, multiple 100- to 160-nm electron lucent vesicles could be observed in the EC cytoplasm. These structures differed from plasmalemmal vesicles and suggest secretory activity. When PMN and monocytes appeared in the vascular lumen (1 h and later), the number of 100-160-nm electron-lucent vesicles had decreased significantly. In contrast to C5a-injected skin sites, mast cell degranulation was absent.
J Invest Dermatol 1991 May
PMID:Inflammatory properties of neutrophil-activating protein-1/interleukin 8 (NAP-1/IL-8) in human skin: a light- and electronmicroscopic study. 202 75

The histological features of biopsies from 18 previously unreported cases of Sweet's syndrome are reported. The dermal infiltrate in the majority of the cases contained numerous histiocytes that at first sight appeared to mimic neutrophils. The immunophenotype of these histiocytes was consistent with monocytes that have freshly infiltrated into the lesions. Only two of the cases in this series, associated with leukaemia, displayed the histological features of Sweet's syndrome with a predominant neutrophilic infiltration. We suggest that the initiating mechanisms in Sweet's syndrome are that monocyte/histiocyte-derived cytokines such as the interleukins IL-1 and IL-8, secreted either by infiltrating histiocytes in the non-leukaemia-associated cases of Sweet's syndrome or by tumoural myelomonocytic cells in those associated with leukaemia, are responsible for the systemic manifestations and the infiltration with neutrophils in the skin lesions.
Br J Dermatol 1991 Apr
PMID:Histiocytes in Sweet's syndrome. 153 89

There is increasing evidence that epidermal cytokines may have an important role in mediating inflammatory and immune responses in the skin. A number of cell types in the epidermis are capable of secreting cytokines including keratinocytes, Langerhans cells, melanocytic cells, and even Merkle cells. Keratinocytes are the major source of cytokines in the epidermis and have been reported to secrete IL-1, IL-3, IL-6, IL-8, CSF, TNF alpha, TGF alpha, TGF beta, and PDGF. Normally these cytokines are not actively secreted by keratinocytes; however, a number of agents are capable of mediating keratinocyte cytokine production, including cytokines themselves. We examined the effect of a number of cytokines on keratinocyte IL-1, IL-6, GM-CSF, and PDGF production. It was found that these keratinocyte cytokines are all modulated by one or more cytokines, including several that keratinocytes themselves secrete. These effects appear to be mediated by high-affinity cytokine receptors on keratinocytes. We are only beginning to understand the molecular mechanisms underlying the production, regulation, and precise role of keratinocyte cytokines in normal and diseased skin; however, recent studies suggest that cytokines secreted by epidermal cells and lymphoid cells may be important modulators of keratinocyte cytokine production.
J Invest Dermatol 1990 Jun
PMID:Cytokine modulation of keratinocyte cytokines. 216 84

In 1986 it was discovered that cultured human keratinocytes, when treated with gamma interferon, attract and bind T lymphocytes and monocytes. More is now known about trafficking of inflammatory cells in the skin, with specific molecular details involving various cytokines, chemotactic factors, and adhesion molecules. One key element is the in vivo movement of T cells that express LFA-1 into the epidermis, and their subsequent binding to keratinocytes via the surface expression of intercellular adhesion molecule-1 (ICAM-1). This interaction represents a common immunologic pathway, which has been identified in a wide variety of different skin diseases. This review provides a synopsis of advances in this field, which have grown rapidly during the past few years, and adds recent results dealing with coordinate regulation at the gene-transcriptional level of keratinocyte chemotactic factor production and adhesion molecule expression. Moreover, epidermal keratinocytes appear to play a pre-eminent role in the skin, serving as transducing elements converting exogenously applied low-molecular-weight chemical stimuli such as phorbol ester and urushiol (the active ingredient in poison ivy extracts) into the production of endogenously derived immunoregulatory proteins. These keratinocyte-derived molecules may then influence immunocytes and endothelial cells to further amplify the inflammatory response. The identification of keratinocyte-derived molecules such as IL-8 and ICAM-1, which influence the chemotaxis and adherence of T cells, adds substantial evidence supporting an active participatory role for keratinocytes in cutaneous immunohomeostasis. Finally, we highlight the importance of these immunoregulatory molecules in two malignant cutaneous disorders (cutaneous T-cell lymphoma and basal-cell carcinoma) and attempt to integrate these new findings into novel pathophysiologic models for two inflammatory dermatoses (rhus dermatitis and psoriasis).
J Invest Dermatol 1990 Jun
PMID:The role of adhesion molecules, chemotactic factors, and cytokines in inflammatory and neoplastic skin disease--1990 update. 219 Oct 50


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