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)

Androstenediol (AED) is a metabolic product of dehydroepiandrosterone (DHEA), an adrenal steroid known to possess immunomodulatory characteristics. The present study was undertaken to assess the efficacy of AED treatment in mice ocularly infected with herpes simplex virus type 1 (HSV-1). The subcutaneous administration of 320 mg/kg AED 4 h prior to viral inoculation was found to enhance the survival of HSV-1-infected mice while lower doses (32.0-100.0 mg/kg) were without effect. However, there were no apparent differences in the viral load in the eye or trigeminal ganglion (TG) 3 or 6 days post infection (p.i.) in vehicle- or AED (320 mg/kg)-treated mice. Likewise, there were no differences in the expression of cytokine or chemokine mRNAs in the eyes or TG early (i.e., 3 days p.i.) following infection. However, by 6 days p.i., there was a significant increase in the expression of the chemokines IP-10, MCP-1, and RANTES and the cytokines interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) in the AED (320 mg/kg)-treated mice compared to vehicle-treated controls as determined by reverse transcription (RT)-polymerase chain reaction (PCR) and quantitative PCR (for IFN-gamma). Likewise, there was a corresponding increase in IFN-gamma and IL-2 but not IL-12 protein in the TG of AED-treated mice 6 days p.i. AED-treatment also induced a rise in splenic natural killer activity in a dose- and time-dependent fashion. Collectively, these results suggest that the protective effect following subcutaneous administration of AED is associated in a rise in selective type 1 cytokines (IL-2 and IFN-gamma) as well as natural killer activity.
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PMID:Increased levels of IFN-gamma in the trigeminal ganglion correlate with protection against HSV-1-induced encephalitis following subcutaneous administration with androstenediol. 972 38

5-Androstenediol (5-AED) stimulates hematopoiesis and enhances survival in animals exposed to ionizing radiation (IR), suggesting that this steroid may act on hematopoietic progenitor cells. We used gamma-irradiated primary human CD34(+) hematopoietic progenitor cells to show that 5-AED protects hematopoietic cells from IR damage, as shown by enhanced cell survival, clonogenicity, proliferation, and differentiation. Unlike in tumor cells, IR did not induce nuclear factor-kappaB (NFkappaB) activation in primary progenitors. However, IR stimulated IkappaB(beta) release from NFkappaB/IkappaB complexes and caused NFkappaB1 (p50) degradation. 5-AED stabilized NFkappaB1 in irradiated cells and induced NFkappaB gene expression and NFkappaB activation (DNA binding). 5-AED stimulated interleukin-6 and granulocyte colony-stimulating factor (G-CSF) secretion. The survival-enhancing effects of 5-AED on clonogenic cells were abrogated by small interfering RNA inhibition of NFkappaB gene expression and by neutralization of G-CSF with antibody. The effects of 5-AED on survival and G-CSF secretion were blocked by the NFkappaB inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132). 5-AED had no effect on accumulation of the proapoptotic factor p53 after IR, as determined by Western blot. The results indicate that NFkappaB1 degradation after IR may be responsible for the radiation sensitivity of CD34+ cells compared with tumor cells. 5-AED exerts survival-enhancing effects on irradiated human hematopoietic progenitor cells via induction, stabilization, and activation of NFkappaB, which results in increased secretion of hematopoietic growth factor G-CSF.
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PMID:5-Androstenediol promotes survival of gamma-irradiated human hematopoietic progenitors through induction of nuclear factor-kappaB activation and granulocyte colony-stimulating factor expression. 1747 57