Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is known that many immunologic responses to IL-1 are antagonized by the neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH). This led us to investigate the possible reciprocal effects of IL-1 and the functionally related epidermal cytokines, epidermal cell-derived thymocyte activating factor (ETAF) and IL-6, on the melanogenic effect of alpha-MSH on murine Cloudman melanoma cells. When these cells were treated with ETAF in combination with alpha-MSH or its potent analog [Nle4,D-Phe7]-alpha-MSH, the melanotropin induced increase in tyrosinase activity, and thus melanin synthesis, was abrogated. This inhibitory effect of ETAF was not mediated by competitive binding to the melanotropin receptor, because ETAF also blocked the melanogenic response of melanoma cells to isobutyl methylxanthine (IBMX) and to PGE1 and PGE2. ETAF had no effect on cellular proliferation. Inhibition of the stimulated tyrosinase activity by ETAF was not due to diminished cAMP synthesis or increased cAMP degradation. Cells treated concomitantly with ETAF and alpha-MSH, IBMX, or PGE1 had the same cAMP levels as cells treated with alpha-MSH, IBMX, or PGE1 alone. In contrast to ETAF, human rIL-1 alpha or IL-1 beta alone or in combination did not have an inhibitory effect on melanogenesis. IL-6 significantly inhibited the basal level of tyrosinase and partially abrogated the alpha-MSH-induced tyrosinase activity. IL-6 also stimulated cellular proliferation when added alone or in combination with alpha-MSH. Granulocyte-macrophage colony stimulating factor (GM-CSF) did not alter either the tyrosinase activity or cellular replication at the concentrations tested. IL-1 alpha, GM-CSF, and IL-6 or IL-1 alpha and GM-CSF added together did not significantly affect the MSH-induced tyrosinase activity. These results ascribe a new potential function for ETAF and IL-6 as modulators of the melanogenic response of pigment cells.
 ...
PMID:A new role for epidermal cell-derived thymocyte activating factor/IL-1 as an antagonist for distinct epidermal cell function. 246 81

Expression of an extended panel of cytokine genes was investigated by reverse polymerase chain reaction (PCR) in 10 freshly excised melanoma metastases infiltrated by lymphocytes (TIL). cDNA encoding for CD3-delta and tyrosinase could be amplified in all samples, confirming the presence of T lymphocytes and melanoma cells. Cytokine genes possibly transcribed by both cell types, such as GM-CSF, IL-6 and IL-10 could be amplified from 5, 2 and 2 samples respectively. In contrast, IL-1 beta and TNF-alpha mRNA were never detectable, IL-1 alpha, IL-3 and IL-7 mRNA could be observed only in one case each. Transcripts encoding for TGF-beta 1 were observed in 8 samples, while TGF-beta 2 and 3 mRNA were detectable in only 2 specimens. mRNA encoding for cytokine genes typically transcribed by antigen-stimulated T lymphocytes, such as IL-2, IL-4 and IFN-gamma were rarely or never detectable (none, none and 1 of the samples respectively). In one case, where no cytokine gene transcription was detectable at the time of surgery, we addressed the question of the antigenicity of the tumor and of the functional competence of TIL. A primary tumor cell line was generated and cultured TIL were induced to transcribe IL-2 and IFN-gamma genes by incubation with the autologous irradiated tumor cell line, but not with autologous EBV-transformed cells. In these conditions, tumor-specific cytotoxic T lymphocytes (CTL) could be generated only after 3 weekly re-stimulations. In contrast, if autologous irradiated EBV-transformed cells were added to the cultures, specific CTL could be detected after one single tumor stimulation. Thus, signs of active responsiveness in terms of lymphokine gene mRNA are seldom detectable in melanoma metastases. Tumor-specific responses, however, including IL-2 and IFN-gamma gene expression and generation of CTL can be produced in vitro from specimens in which no cytokine gene mRNA is detectable ex vivo.
 ...
PMID:The pattern of cytokine gene expression in freshly excised human metastatic melanoma suggests a state of reversible anergy of tumor-infiltrating lymphocytes. 818 65