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)

Most of the matrix metalloproteinases (MMP) are not expressed in normal intact skin but they are upregulated in inflamed or diseased skin. The recently cloned MMP-19 is one of the few MMP members that are also expressed in healthy epidermis. In this study, we found that MMP-19 is generally coexpressed with cytokeratin 14 that is confined to keratinocytes of the stratum basale. MMP-19 was also detected in hair follicles, sebaceous glands, and eccrine sweat glands. Its expression, however, changed in cutaneous diseases exhibiting increased alternations of epidermal proliferation, such as psoriasis, eczema, and tinea. In the affected area, MMP-19 was also found in suprabasal and spinous epidermal layers. We also studied the regulation of MMP-19 expression at the protein level, as well as by using a promoter assay. The constitutive expression of MMP-19 was upregulated with phorbol myristate acetate and downregulated with retinoic acid and dexamethasone. Tumor necrosis factor-alpha, interleukin (IL)-6, TGF-beta, IL-15, IL-8, and RANTES as well as the bacterial compounds lipopolysaccharide and lipoteichoic acid did not show any profound effect in HaCaT cells. In contrast, type IV and type I collagens upregulated MMP-19 significantly. The dysregulation of MMP-19 expression in epidermis suggests its possible involvement in the perpetuation of cutaneous infections and proliferative disorders such as psoriasis.
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PMID:Matrix metalloproteinase-19 expression in normal and diseased skin: dysregulation by epidermal proliferation. 1470 97

Dermatophytosis (tinea) is a common disease in superficial mycoses and is generally confined to the stratum corneum in the epidermis and cutaneous appendages. The mechanisms by which dermatophytes cause dermatophytosis, however, are poorly understood. In this study, we evaluated the effect of Trichophyton mentagrophytes, T. tonsurans and T. rubrum on cytokine production by normal human epidermal keratinocytes (NHEKs). After 3-24 h of co-culture of NHEKs with each of the dermatophytes, cytokines in the supernatant were measured by enzyme-linked immunosorbent assay. Promoter activity of IL-8 was measured by chloramphenicol acetyl transferase (CAT) assay. IL-8 and GRO-alpha levels were higher in supernatants co-cultured with T. mentagrophytes isolates from animal than in those with T. mentagrophytes isolates from human, and with T. tonsurans and T. rubrum isolates. CAT expression for IL-8 promoter activity was higher in cell lysates stimulated with T. mentagrophytes isolates from animal than in those with T. mentagrophytes isolates from human, and with T. tonsurans and T. rubrum isolates. These findings suggest that dermatophytes directly induce production of cytokines at the transcriptional level by human keratinocytes, and that there are differences in their ability to induce cytokine production between the dermatophytes.
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PMID:The effect of dermatophytes on cytokine production by human keratinocytes. 1771 Apr 24