Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arachidonic acid (AA) activates the 5-lipoxygenase, induces leukotriene-B(4) (LTB(4)) synthesis, enhances interleukin-6 (IL-6) release and increases intracellular neutral lipids in human sebocytes. Moreover, the enzymes of LTB(4) biosynthesis are activated in acne-involved sebaceous glands. Zileuton a 5-lipoxygenase inhibitor, reduces the number of inflammatory acne lesions and lipogenesis in patients with acne. In this study, we investigated the activity of zileuton on LTB(4) generation, lipid content and IL-6 and -8 release from human SZ95 sebocytes in vitro. Pretreatment with zileuton partially prevented the AA-induced LTB(4) and IL-6 release and increased neutral lipid content. IL-6 release and neutral lipid content were also reduced under long-term zileuton treatment. In conclusion, zileuton prevents the activation of the leukotriene pathway and enhancement of lipogenesis by AA in human sebocytes in vitro.
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PMID:Zileuton prevents the activation of the leukotriene pathway and reduces sebaceous lipogenesis. 1964 54

Tissue inflammation is a major component of the acne process. Leukotriene B(4) (LTB(4)) is considered to be a major player in the development of tissue inflammation. Synthesis of LTB(4) is controlled by the enzyme 5-lipoxygenase. Since Zileuton blocks the activity of 5-lipoxygenase, experimental and clinical studies have been conducted to test mode of function, as well as efficacy and safety of this compound in the treatment of acne vulgaris. Human SZ95 sebocytes and inflammatory cells in vitro express the enzymes of the leukotriene pathway at mRNA and protein levels and enzymes involved in the biosynthesis of LTB(4) are activated in sebaceous glands of acne lesions. Pre-treatment of SZ95 sebocytes with Zileuton partially prevented short-term arachidonic acid-induced effects, such as induction of LTB(4), increase of neutral lipid content and stimulation of interlekin-6 release. Long-term treatment with Zileuton directly reduced the content of neutral lipids and interleukin-6 release from SZ95 seb ocytes. PPAR mRNA levels were not regulated by Zileuton. In a first pilot clinical study with 10 patients with papulopustular acne Zileuton 4 x 600 mg/d p.o. for 3 months decreased the acne severity index in a time-dependent manner being 41% of the initial score at week 12 (p < 0.05). This was mostly due to a decrease of the number of inflammatory lesions of 29% (p < 0.01). In addition, total sebum lipids significantly decreased (35%, p < 0.05) and the pro-inflammatory free fatty acids (22%) and lipoperoxides (26%) were markedly diminished in patients' sebum under treatment. The magnitude of clinical improvement strongly correlated with the reduction of total sebum lipids (p = 0.0009, r(2) = 0.81) and free fatty acids (p = 0.0003, r(2) = 0.82). In a further study, a 40-year-old female with mild disseminated sebaceous gland hyperplasia and seborrhea, responded with normalization of the casual skin surface lipids and similar reduction of facial sebum synthesis under treatment with Zileuton over 2weeks and-after a wash-out phase-low-dose isotretinoin (10 mg/2nd d) over 5 weeks. These data are in agreement with a phase II multicenter, clinical study in 101 patients with mild to moderate inflammatory facial acne conducted in the US, which showed a significant efficacy of Zileuton in a subset of patients with moderate acne, whereas those patients treated with Zileuton showed a significant mean decrease in inflammatory lesions compared to the placebo group. In all clinical studies, Zileuton was found to be safe and well tolerated.
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PMID:Zileuton, a new efficient and safe systemic anti-acne drug. 2043 87

Stroke is one of the most frequent causes of death and disability worldwide causing a major clinical and socioeconomic impact. Although the pathophysiology of brain ischemia and reperfusion is complex, the inflammatory process plays an important role in pathogenesis, contributing to the expansion of brain injury. The 5-lipoxygenase (5-LOX) is a key enzyme in the biosynthesis of the leukotrienes and has been implicated and in the central nervous system (CNS) disorders such as Alzheimer's disease and acute ischemic stroke. Zileuton, a selective 5-LOX inhibitor, has antiinflammatory properties and exerts an inhibitory effect on inflammatory diseases. The objective of this study was to evaluate the effects of blocking 5-LOX activity in a murine model of transient and global brain ischemia. Zileuton improved neurological deficits and significantly decrease volume and density of lesion, compared to vehicle-ischemic animals measured by magnetic resonance imaging (MRI). In addition, the blockage of 5-LOX reduced infarct area and histopathological changes. Furthermore, by enzyme immunoassay (ELISA) increased brain levels of tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-C motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5) were detected in the vehicle-ischemic group, whereas in Zileuton-ischemic group presented reduction of these mediators. The concentration of the antiinflammatory cytokine interleukin-10 (IL-10) was increased after 5-LOX inhibition. Our results suggest that Zileuton decreases brain damage and reduces inflammatory cytokines expression in the CNS which contributes, at least in part, to improve the neurological outcome of brain ischemia.
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PMID:The 5-lipoxygenase (5-LOX) Inhibitor Zileuton Reduces Inflammation and Infarct Size with Improvement in Neurological Outcome Following Cerebral Ischemia. 2626 53