Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For the first time the complete cDNA encoding a major allergen and novel protein of the yeast Malassezia furfur, Mal f 1, has been sequenced and expressed. The amino acid sequences of nine tryptic peptides of the protein were determined. Oligonucleotides were designed from these amino acid sequences. The cDNA sequence was obtained by hybridizing these primers to mRNA and enhancement by reverse-transcriptase PCR techniques. The cDNA is 1176 bp in length. It shows an open reading frame of 1050 bp coding for a protein of 38178 Da and a deduced amino acid sequence containing 350 residues. The hydropathy plot and the tryptic digest indicate that the first 22 amino acids represent a leader sequence determining a mature protein of 35 988 Da. The complete encoding cDNA was expressed as a maltose-binding protein fusion protein in Escherichia coli. The recombinant fusion protein reacted with our specific monoclonal antibody and with IgE from patients with atopic dermatitis.
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PMID:The complete cDNA sequence and expression of the first major allergenic protein of Malassezia furfur, Mal f 1. 921 Apr 81

Epidermal cytokines such as interleukin (IL)-1beta, tumor necrosis factor-alpha, and IL-12 have been described to play a crucial role in the induction and elicitation phase of allergic contact dermatitis upon exposure to haptens. In this study we asked whether these cytokines may also play a role in the epidermis of patients with atopic dermatitis after the application of house dust mite antigens (HDM) to their skin. Epidermal samples were collected by scraping healthy appearing skin of atopic patients and healthy individuals 8 h after the application of an extract of HDM. Sodium lauryl sulfate and saline served as controls. Reverse transcriptase-polymerase chain reaction was performed for IL-1beta, tumor necrosis factor-alpha, IL-12 p35, and IL-12 p40. Exposure to HDM led to a significant upregulation of mRNA of these cytokines in atopic patients only. Whereas IL-1beta and tumor necrosis factor-alpha also showed an upregulation in part of these patients after exposure to the irritant sodium lauryl sulfate, IL-12 p40 mRNA was exclusively enhanced by the application of the allergen. In contrast to IL-12 p40, IL-12 p35 mRNA was not detectable in significant amounts. Interestingly, also in untreated, normal appearing skin of atopic individuals (n = 16), the levels of these cytokines were higher than in normal individuals (n = 8), possibly explaining the increased skin irritability of atopic individuals. Finally, comparing epidermal cytokines in the skin of patients who developed a positive allergen patch test to those who stayed negative, suggests that only expression of IL-1beta mRNA may be a predictive marker for the development of a positive patch test reaction to HDM.
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PMID:Epidermal cytokines IL-1beta, TNF-alpha, and IL-12 in patients with atopic dermatitis: response to application of house dust mite antigens. 985 37

The objectives of the present study were to characterize and compare the repertoire of cytokine-genes transcribed in skin homogenates obtained from normal dogs and dogs with atopic dermatitis (AD) using a reverse-transcriptase polymerase chain reaction and canine-specific cytokine-gene primers. Whereas IL-4 and IL-5 cytokine-gene transcripts were detected more commonly in atopic skin biopsy homogenates, IL-2 mRNA was amplified more often from normal control specimens. IFN-gamma mRNA was detected in 5/29 atopic specimens, 4 of them obtained from the only dog with chronic skin lesions. One-fourth of atopic samples exhibited clear type-2 cytokine profiles; the remainder did not demonstrate polarized repertoires. Conversely, type-1 cytokine profiles were characterized in one-fourth of normal control specimens. The present study establishes, for the first time, the transcription of type-2 cytokine-genes in the skin of dogs with AD. Future experiments investigating the cellular origin and dynamics of allergic cytokine-gene transcription are needed to confirm whether or not canine AD could be considered an immunological model for a human disease.
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PMID:Toward a canine model of atopic dermatitis: amplification of cytokine-gene transcripts in the skin of atopic dogs. 1038 38

CC chemokine receptors are expressed on hematopoietic cells, and these may impart selective homing of monocyte, leukocyte, and lymphocyte subsets to sites of inflammation. CC chemokine receptor 3 is the major receptor on eosinophils and is also expressed on other inflammatory cells suggesting its important role for allergic diseases such as atopic dermatitis and bronchial asthma. Eotaxin, eotaxin-2 and eotaxin-3 have been identified as ligands that only activate CC chemokine receptor 3. CC chemokine receptor 3 is also activated by other promiscuous ligands, however, such as RANTES and monocyte chemotactic protein 4. To date, CC chemokine receptor 3 has not been reported to be expressed on nonhematopoietic cells. In this study, we investigated whether keratinocytes possess autocrine and paracrine mechanisms for CC chemokine secretion and receptor expression as reported for the expression of interleukin 8 and its receptors. Reverse transcriptase polymerase chain reaction analysis demonstrated that CC chemokine receptor 3 mRNA is expressed constitutively in cultured keratinocytes. The signal quantities of the CC chemokine receptor 3 amplicons showed lower intensities for keratinocytes than for eosinophils. In situ hybridization techniques exhibited that basal cell layers of the epidermis were stained homogeneously for CC chemokine receptor 3 mRNA with a decreasing signal to the upper epidermis showing that differentiating and proliferating keratinocytes did express mRNA specific for CC chemokine receptor 3. Immunohistochemical studies confirmed low expression of CC chemokine receptor 3 protein on epidermal keratinocytes compared to the high level observed on infiltrating eosinophils. Furthermore, stimulation of cultured keratinocytes with eotaxin resulted in an increased [3H]thymidine incorporation indicating a role of CC chemokine receptor 3 in epidermal proliferation and differentiation. These data demonstrate that CC chemokine receptor 3 is expressed not only on hematopoietic cells but also on keratinocytes as nonhematopoietic cells with ectodermal origin. Therefore, the identification of CC chemokine receptor 3 on epidermal keratinocytes may indicate a role for CC chemokine receptor 3 and its ligands in skin physiology and pathophysiology.
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PMID:Characterization of the CC chemokine receptor 3 on human keratinocytes. 1128 22

Malassezia species are opportunistic yeasts that are involved in the pathogenesis of a number of skin diseases including atopic eczema/dermatitis syndrome. Previously, we cloned six allergens from Malassezia sympodialis isolate ATCC 42132; these allergens are designated Mala s 1, and Mala s 5-Mala s 9. Three additional allergens, Mala f 2-Mala f 4, have been isolated from M. furfur by other investigators. The objective of the present study was to investigate the presence of these Mala sequences in seven Malassezia species. Genomic DNA amplification by PCR and sequencing showed that M. globosa, M. obtusa and M. sympodialis contain DNA sequences corresponding to all the allergens except Mala f 2 and Mala f 3. M. pachydermatis contains Mala s 1, Mala f 4, and Mala s 5-Mala s 8. M. restricta and M. slooffiae possessed Mala f 4 and Mala s 6. M. furfur was seen to possess Mala f 2-Mala f 4 as well as Mala s 5-Mala s 7. Our data from reverse-transcriptase PCR showed a more species-specific pattern of amplification. M. furfur evidenced expression of Mala f 2-Mala f 4. M. globosa and M. obtusa appeared to express only Mala s 6. M. pachydermatis expressed Mala f 4, Mala s 6, and Mala s 8, while M. restricta and M. slooffiae expressed Mala f 4 and Mala s 6. M. sympodialis expressed all the allergens except Mala f 2 and Mala f 3. Different Malassezia species appear to contain both common and species-specific allergen sequences.
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PMID:Detection of Mala f and Mala s allergen sequences within the genus Malassezia. 1567 71

Eotaxin plays a central role in the development of allergic disease, including atopic dermatitis, asthma, and nasal allergy. Interleukin (IL)-4 induces eotaxin production in normal human dermal fibroblasts. On the other hands, Transforming growth factor-beta (TGF-beta), a multifunctional regulatory cytokine, affects many biological functions, including fibroblast growth and differentiation and Th2 cytokine regulation. In this study, we investigated the effect of TGF-beta on IL-4-induced eotaxin production by normal human fibroblasts, as well as the effect of suplatast tosilate, an antiallergic drug that selectively inhibits Th2 cytokine production. Dermal fibroblast treatment with IL-4 and TGF-beta for 24 h increased eotaxin production and expression of eotaxin mRNA, as measured by enzyme-linked immunosorbent assay (ELISA) and reverse-transcriptase polymerase chain reaction (RT-PCR), respectively. TGF-beta synergistically up-regulated eotaxin production and eotaxin mRNA expression when stimulated with IL-4. Suplatast tosilate dose-dependently inhibited eotaxin production induced by IL-4 or IL-4 plus TGF-beta. These results suggest that TGF-beta may regulate skin allergic inflammation by up-regulating eotaxin production in dermal fibroblasts. Suplatast tosilate might suppress this inflammation by inhibiting eotaxin production.
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PMID:Increase effect of transforming growth factor on eotaxin production by normal cultured dermal fibroblasts stimulated with interleukin-4: inhibitory effect of suplatast tosilate on eotaxin production. 2013 17