Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis is an inducible suicide program that occurs in all phases of multicellular as well as in protozoa life and gains more and more importance in all medical disciplines. It is required for normal ontogenesis, organ and tissue remodeling, function of the immune system, prevention of inappropriate cellular proliferation and of survival of inappropriate mutations. Thereby apoptosis represents the key event which guarantees differentiation and maintenance of homeostasis. Terminal differentiation seems to be a special form of apoptosis. Dysregulated apoptosis is associated with various pathological conditions, including inflammation, and cancer. Acanthosis, the hallmark of psoriatic skin, is an example for diminished epidermal apoptosis. Defects in termination of inflammatory reactions occur in atopic dermatitis. Lupus erythematosus may arise due to disturbed apoptosis on several check points of the apoptosis cascade. Experimental evidence suggests a role for Bcl-2 and CD95L in the inhibition of programmed cell death in UV-induced skin cancer or malignant melanoma cells. Thus, it leads to survival of malignant cell clones. The slow growth of basal cell carcinomas is due to an increased apoptosis to mitosis ratio. Spontaneous regression of tumors is associated with increased apoptotic rates. Malignant melanoma cells characteristically show different anti-apoptotic strategies which underscore its aggressive behavior and its refractory towards classic therapeutic regimens. Additionally, induction of apoptosis in tumor infiltrating immune cells seems to be a strategy by which the tumor escapes from an immunological attack (tumor counter-attack). Since apoptosis is either absent or altered under pathological conditions therapeutic procedures should correct this. Established therapies like dithranol, vitanin-D3 analogs, low-dose methotrexate, induce apoptosis. Future treatment regimens like vaccine and gene therapy are designed to selectively induce apoptosis. Therefore, pharmacological agents and therapeutic strategies interfering with disrupted apoptosis regulation could improve the therapeutic arsenal in the future.
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PMID:Apoptosis in physiological and pathological skin: implications for therapy. 1690 Jun 61

There exists several reports where malignant melanoma is associated with vitiligo, vitiligo with discoid lupus erythematosus and lupus erythematosus with urticaria. However, there are no reports in which vitiligo, malignant melanoma, lupus erythematosus and urticaria coexist in the same case. Herein, we report a case of a patient who developed lupus erythematosus, malignant melanoma, vitiligo and urticaria simultaneously.
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PMID:Vitiligo associated with malignant melanoma and lupus erythematosus. 1723 55

Innate immune receptors that recognize nucleic acids, such as TLRs and RNA helicases, are potent activators of innate immunity that have been implicated in the induction and exacerbation of autoimmunity and inflammatory arthritis. Polyriboinosine-polyribocytidylic acid sodium salt (poly(IC)) is a mimic of dsRNA and viral infection that activates TLR3 and the RNA helicases retinoic acid-induced gene-1 and melanoma differentiation-associated gene-5, and strongly induces type I IFN production. We analyzed the effects of systemic delivery of poly(IC) on the inflammatory effector phase of arthritis using the collagen Ab-induced and KRN TCR-transgenic mouse serum-induced models of immune complex-mediated experimental arthritis. Surprisingly, poly(IC) suppressed arthritis, and suppression was dependent on type I IFNs that inhibited synovial cell proliferation and inflammatory cytokine production. Administration of exogenous type I IFNs was sufficient to suppress arthritis. These results suggest a regulatory role for innate immune receptors for dsRNA in modulating inflammatory arthritis and provide additional support for an anti-inflammatory function of type I IFNs in arthritis that directly contrasts with a pathogenic role in promoting autoimmunity in systemic lupus.
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PMID:Suppression of the effector phase of inflammatory arthritis by double-stranded RNA is mediated by type I IFNs. 1727 25

Sphingolipids have long been viewed as rather passive structural components of cellular membranes. More recently, it has become evident that metabolism of sphingomyelin yields several lipid mediators that evoke diverse and specific responses in different cell types. One sphingomyelin derivate, sphingosine-1-phosphate (S1P), has attracted particular attention for its effect on epidermal cells, which differs from those on most other cell types. S1P inhibits keratinocyte proliferation and induces keratinocyte differentiation and migration, suggesting a role for S1P in the re-epithelialization of wounds. The migratory response involves the phosphorylation and activation of Smad3. In epithelial tumors, S1P signaling has been linked with potential oncogenic effects, but has also been found to inhibit metastasis in a mouse melanoma model. S1P promotes endothelial cell survival, acts as a chemoattractant for vascular cells, and exerts a protective effect on the endothelial barrier. Conversely, S1P receptor knockout leads to embryonic lethality mainly due to impaired vascular maturation. S1P presumably modulates peripheral T-lymphocyte levels by stimulating their egress from lymphoid organs rather than by promoting T-cell proliferation. The S1P analog FTY720 (fingolimod) acts as a functional antagonist by inhibiting lymphocyte egress, and thus holds great promise as an immunosuppressant drug for the prevention of allograft rejection and treatment of T-lymphocyte-driven inflammatory skin diseases, such as lupus erythematosus, psoriasis, and atopic dermatitis. Topical use of S1P and other sphingosine compounds is also under investigation, particularly for the treatment of acne vulgaris.
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PMID:Sphingosine-1-phosphate signaling and the skin. 1803 15

In recent years, DNA microarray technology has been used for the analysis of gene expression patterns in a variety of skin diseases, including malignant melanoma, psoriasis, lupus erythematosus, and systemic sclerosis. Many of the studies described herein confirmed earlier results on individual genes or functional groups of genes. However, a plethora of new candidate genes, gene patterns, and regulatory pathways have been identified. Major progresses were reached by the identification of a prognostic gene pattern in malignant melanoma, an immune signaling cluster in psoriasis, and a so-called interferon signature in systemic lupus erythematosus. In future, interference with genes or regulatory pathways with the use of different RNA interference technologies or targeted therapy may not only underscore the functional significance of microarray data but also may open interesting therapeutic perspectives. Large-scale gene expression analyses may also help to design more individualized treatment approaches of cutaneous diseases.
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PMID:DNA microarray technology in dermatology. 1848 20

Selected health hazards of outdoor work are reported. The hazards are attributable to physical agents (cold and hot microclimate, UV radiation), chemical agents (e.g., pesticides and herbicides, exhaust fumes), fine particulate dust, biological agents (insect bites, organic dusts, bacteria, poisonous vegetables), excessive physical (static and dynamic) loads. Exposures to those agents may cause circulatory diseases (arterial hypertension, ischemic heart disease), symptoms of lower and upper spine or renal calculosis. Particular attention was paid to dermal diseases caused by exposure to solar radiation, such as sunburns, idiopathic dermatoses, chronic lesions, exacerbation of other skin diseases (lupus erythematosus, porphyria), phototoxic and photoallergic reactions, melanoma and nonmelanoma skin cancer. Besides, solar radiation causes premature skin ageing and premalignant lesions (lentigo maligna, solar keatosis).
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PMID:[Outdoor work-related health hazards]. 1938 63

Osteopontin (OPN) is a glycoprotein expressed by various tissues and cells. The existence of variant forms of OPN as a secreted (sOPN) and intracellular (iOPN) protein and its modification through post-translational modification and proteolytic cleavage explain its broad range of functions. There is increasing knowledge which receptors OPN isoforms can bind to and which signaling pathways are activated to mediate different OPN functions. sOPN interacts with integrins and CD44, mediates cell adhesion, migration and tumor invasion, and has T helper 1 (Th1) cytokine functions and anti-apoptotic effects. iOPN has been described to regulate macrophage migration and interferon-alpha secretion in plasmacytoid dendritic cells. Both sOPN and iOPN, through complex functions for different dendritic cell subsets, participate in the regulation of Th cell lineages, among them Th17 cells. For skin disease, OPN from immune cells and tumor cells is of pathophysiological relevance. OPN is secreted in autoimmune diseases such as lupus erythematosus, and influences inflammation of immediate and delayed type allergies and granuloma formation. We describe that OPN is overexpressed in psoriasis and propose a model to study OPN function in psoriatic inflammation. Through cytokine functions, OPN supports immune responses against Mycobacteria and viruses such as herpes simplex virus. OPN is also implicated in skin tumor progression. Overexpression of OPN influences invasion and metastasis of melanoma and squamous cell carcinoma cells, and OPN expression in melanoma is a possible prognostic marker. As OPN protein preparations and anti-OPN antibodies may be available in the near future, in-depth knowledge of OPN functions may open new therapeutic approaches for skin diseases.
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PMID:Osteopontin and the skin: multiple emerging roles in cutaneous biology and pathology. 1955 97

Double-stranded (ds) DNA, DNA- or RNA-associated nucleoproteins are the primary autoimmune targets in SLE, yet their relative inability to trigger similar autoimmune responses in experimental animals has fascinated scientists for decades. While many cellular proteins bind non-specifically negatively charged nucleic acids, it was discovered only recently that several intracellular proteins are involved directly in innate recognition of exogenous DNA or RNA, or cytosol-residing DNA or RNA viruses. Thus, endosomal Toll-like receptors (TLR) mediate responses to double-stranded RNA (TLR-3), single-stranded RNA (TLR-7/8) or unmethylated bacterial cytosine (phosphodiester) guanine (CpG)-DNA (TLR-9), while DNA-dependent activator of IRFs/Z-DNA binding protein 1 (DAI/ZBP1), haematopoietic IFN-inducible nuclear protein-200 (p202), absent in melanoma 2 (AIM2), RNA polymerase III, retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) mediate responses to cytosolic dsDNA or dsRNA, respectively. TLR-induced responses are more robust than those induced by cytosolic DNA- or RNA- sensors, the later usually being limited to interferon regulatory factor 3 (IRF3)-dependent type I interferon (IFN) induction and nuclear factor (NF)-kappaB activation. Interestingly, AIM2 is not capable of inducing type I IFN, but rather plays a role in caspase I activation. DNA- or RNA-like synthetic inhibitory oligonucleotides (INH-ODN) have been developed that antagonize TLR-7- and/or TLR-9-induced activation in autoimmune B cells and in type I IFN-producing dendritic cells at low nanomolar concentrations. It is not known whether these INH-ODNs have any agonistic or antagonistic effects on cytosolic DNA or RNA sensors. While this remains to be determined in the future, in vivo studies have already shown their potential for preventing spontaneous lupus in various animal models of lupus. Several groups are exploring the possibility of translating these INH-ODNs into human therapeutics for treating SLE and bacterial DNA-induced sepsis.
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PMID:Nucleic acid sensing receptors in systemic lupus erythematosus: development of novel DNA- and/or RNA-like analogues for treating lupus. 2045 14

Interleukin-21 (IL-21) is a potent immunomodulatory cytokine, with pleiotropic effects on both innate and adaptive immune responses. These actions include positive effects, such as enhanced proliferation of lymphoid cells, increased cytotoxicity of CD8(+) T cells and natural killer cells, and differentiation of B cells into plasma cells. IL-21 is also produced by Th17 cells and is a critical regulator of Th17 development. IL-21 has potent antitumor activity, but is also associated with the development of autoimmune disease. Many of these activities are critically involved in the pathogenesis of several skin diseases such as psoriasis, atopic dermatitis, lupus erythematosus, and melanoma. Here we review recent advancements on the understanding of the role of IL-21 in skin diseases and how this knowledge can be translated into innovative therapeutic approaches.
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PMID:IL-21 in the pathogenesis and treatment of skin diseases. 2088 35

Twins have always fascinated medical research even before the discovery of DNA and the understanding of the differences between identical and non-identical twins. Dermatology with the benefit of being able to visualize phenotypes was one of the first specialities reporting on the fascinating concordance in identical (MZ) twins in the 1920's. Over the last 20 years, the heritability of skin diseases using twins has been clearly demonstrated, across a wide variety of traits including melanoma, polymorphic light eruption, psoriasis, eczema and acne. Other rarer diseases have also been shown to have a significant genetic basis such as lupus, sarcoidosis and lichen sclerosus. Following evidence of heritability for many skin disease the next step was Genome-Wide Association Studies (GWAS) which are uncovering new genes in large twin cohorts. The twin model is also ideal for the new field of epigenetics, investigating subtle differences in DNA methylation within discordant MZ pairs for a disease, as well as differences in CNVs. Twins are also valuable for examining differences in gene function via RNA expression in twins discordant for a skin trait or disease.
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PMID:The use of the twin model to investigate the genetics and epigenetics of skin diseases with genomic, transcriptomic and methylation data. 2224 46


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