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)

While the impact of the dengue viruses on liver function is prominent as shown by hepatomegaly, liver enzyme abnormality, occasional fulminant hepatic failure and histological changes including hepatocellular necrosis, significant debate exists as to the possible involvement of the predominant cell type in the liver, hepatocytes, in the disease process. To address this issue purified human primary hepatocytes were exposed to dengue virus serotype 2 and the production of de novo viral progeny was established by standard plaque assay, RT-PCR and immunocytochemistry. To investigate the response of the primary hepatocytes to infection, the expression of a panel of 9 cytokine genes (IFN-beta, TRAIL, MCP-1, IL-6, IL-1beta, IL-8, MIP-1alpha, MIP-1beta, and RANTES) was semi-quantitatively investigated by RT-PCR and up-regulation of TRAIL, MIP-1alpha, IFN-beta, MIP-1beta, IL-8, and RANTES was observed in response to infection. The induction of IL-8 in response to infection was accompanied by the secretion of IL-8 as verified by ELISA assay. The ability of hepatocytes to be infected with dengue virus serotype 2 in vitro support evidence implicating human hepatocytes as a target cell in cases of dengue virus infection, and provide the first experimental evidence to support the large number of clinical studies that implicate the liver as a critical target organ in severe cases of dengue infection.
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PMID:Infection of human primary hepatocytes with dengue virus serotype 2. 1724 28

Arsenicosis is a multisystem disorder, with virtually no system spared from its vicious claw; though its predominant manifestations are linked to cutaneous involvement. Cutaneous effects take the form of pigmentary changes, hyperkeratosis, and skin cancers (Bowen's disease, squamous cell carcinoma, and basal cell epithelioma). Peripheral vascular disease (blackfoot disease), hypertension, ischemic heart disease, noncirrhotic portal hypertension, hepatomegaly, peripheral neuropathy, respiratory and renal involvement, bad obstetrical outcome, hematological disturbances, and diabetes mellitus are among the other clinical features linked to arsenic toxicity. The effects are mediated principally by the trivalent form of arsenic (arsenite), which by its ability to bind with sulfhydryl groups present in various essential compounds leads to inactivation and derangement of body function. Though the toxicities are mostly linked to the trivalent state, arsenic is consumed mainly in its pentavalent form (arsenate), and reduction of arsenate to arsenite is mediated through glutathione. Body attempts to detoxify the agent via repeated oxidative methylation and reduction reaction, leading to the generation of methylated metabolites, which are excreted in the urine. Understandably the detoxification/bio-inactivation process is not a complete defense against the vicious metalloid, and it can cause chromosomal aberration, impairment of DNA repair process, alteration in the activity of tumor suppressor gene, etc., leading to genotoxicity and carcinogenicity. Arsenic causes apoptosis via free radical generation, and the cutaneous toxicity is linked to its effect on various cytokines (e.g., IL-8, TGF-beta, TNF-alpha, GM-CSF), growth factors, and transcription factors. Increased expression of cytokeratins, keratin-16 (marker for hyperproliferation) and keratin-8 and -18 (marker for less differentiated epithelial cells), can be related to the histopathological findings of hyperkeratosis and dysplastic cells in the arsenicosis skin lesion.
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PMID:Pathogenesis, clinical features and pathology of chronic arsenicosis. 1917 78