Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we have tested the ability of coal dust to stimulate kinase phosphorylation of activator protein-1 (AP-1) signal transduction pathways and production of interleukin-6 (IL-6) in both mouse epidermal JB6 and human lung epithelial A549 cells. Seven coal samples from three coalmine regions of Pennsylvania (PA), West Virginia (WV), and Utah (UT) with high, medium, and low prevalence of coal workers' pneumoconiosis (CWP), respectively, were investigated. Results from the present study indicate that three PA coals stimulated the mitogen-activated protein kinase (MAPK) family of extracellular signal-regulated kinases (ERKs) and p38 MAPK, but not c-Jun-NH2-terminal kinases (JNKs) in human lung A549 cells. The effects of three UT coals on the kinase phosphorylation were less as compared to those of the PA coals. Coal dusts from three coalmine regions induced IL-6 in a dose-dependent manner in both JB6 and A549 cells. Interestingly, levels of IL-6 in both cells treated with coals from three coalmine regions correlated well with CWP prevalence from that region. To assess the role of AP-1 pathways in coal-mediated transcriptional activation of IL-6, various inhibitors were used in cells treated with one PA coal, which induced a maximal response. It was found that the increase in IL-6 protein and mRNA by the PA coal was completely eliminated by the pretreatment of both cell types with PD98059, a specific MEK1 inhibitor, and SB202190, a p38 kinase inhibitor. Our results indicate that coal dust can stimulate IL-6 release from mouse epidermal JB6 cells and human lung epithelial A549 cells, and the coal-induced IL-6 increase may involve ERKs and p38 MAPK pathways.
 ...
PMID:Coal-induced interleukin-6 gene expression is mediated through ERKs and p38 MAPK pathways. 1291 2

We recently cloned a c-Jun amino-terminal kinase (JNK) sequence from the C6/36 cell line, derived from the mosquito Aedes albopictus. We showed that SP600125, an inhibitor of JNK proteins, inhibits phagocytosis by C6/36 cells, suggesting that the JNK-like protein regulates phagocytosis. Here, we show that C6/36 cells constitutively express low levels of mRNA encoding the antibacterial peptides, cecropin and defensin, but that these mRNAs were up-regulated upon stimulation by lipopolysaccharide (LPS). Thus, the C6/36 cells have properties similar to those of mammalian macrophages. To characterize further the functional properties of C6/36 cells, we have assayed the role of the JNK-like protein in phagocytosis, endocytosis, and viral infection. C6/36 cells phagocytosed bacteria and artificial beads, and this was only slightly up-regulated following LPS stimulation, suggesting that newly stimulated JNK-like protein was not necessary for phagocytosis. SP600125 inhibited the acidification of intracellular compartments, including those involved in the endocytic pathway. Pretreatment of C6/36 cells with SP600125 or bafilomycin A1, but not cytochalasin D, inhibited the entry of West Nile virus (WNV), suggesting that WNV is internalized mainly by endocytosis, and that the JNK signalling pathway is important for endocytic entry. These findings indicate that the JNK-like protein regulates basic physiological functions, including phagocytosis and endocytosis and infection of WNV.
 ...
PMID:Involvement of the JNK-like protein of the Aedes albopictus mosquito cell line, C6/36, in phagocytosis, endocytosis and infection of West Nile virus. 1297 54

Interferon regulatory factors (IRF)-3 and IRF-7 are master transcriptional factors that regulate type I IFN gene (IFN-alpha/beta) induction and innate immune defenses after virus infection. Prior studies in mice with single deletions of the IRF-3 or IRF-7 genes showed increased vulnerability to West Nile virus (WNV) infection. Whereas mice and cells lacking IRF-7 showed reduced IFN-alpha levels after WNV infection, those lacking IRF-3 or IRF-7 had relatively normal IFN-b production. Here, we generated IRF-3(-/-)x IRF-7(-/-) double knockout (DKO) mice, analyzed WNV pathogenesis, IFN responses, and signaling of innate defenses. Compared to wild type mice, the DKO mice exhibited a blunted but not abrogated systemic IFN response and sustained uncontrolled WNV replication leading to rapid mortality. Ex vivo analysis showed complete ablation of the IFN-alpha response in DKO fibroblasts, macrophages, dendritic cells, and cortical neurons and a substantial decrease of the IFN-beta response in DKO fibroblasts and cortical neurons. In contrast, the IFN-beta response was minimally diminished in DKO macrophages and dendritic cells. However, pharmacological inhibition of NF-kappaB and ATF-2/c-Jun, the two other known components of the IFN-beta enhanceosome, strongly reduced IFN-beta gene transcription in the DKO dendritic cells. Finally, a genetic deficiency of IPS-1, an adaptor involved in RIG-I- and MDA5-mediated antiviral signaling, completely abolished the IFN-beta response after WNV infection. Overall, our experiments suggest that, unlike fibroblasts and cortical neurons, IFN-beta gene regulation after WNV infection in myeloid cells is IPS-1-dependent but does not require full occupancy of the IFN-beta enhanceosome by canonical constituent transcriptional factors.
 ...
PMID:Induction of IFN-beta and the innate antiviral response in myeloid cells occurs through an IPS-1-dependent signal that does not require IRF-3 and IRF-7. 1979 31

Arsenic is a well-established human carcinogen; however molecular mechanisms to arsenic-induced carcinogenesis are complex and elusive. The present study identifies a potential biomarker of arsenic exposure, and redefines arsenic-induced signaling in stimulation of cell proliferation. The effect of arsenic exposure on gene expression was evaluated in PBMC of arsenic-exposed individuals selected from a severely affected district of West Bengal, India. A novel, un-documented biomarker of arsenic exposure, CyclinA was identified by microarray analysis from the study. Non-transformed cell lines HaCat and Int407 when exposed to clinically achievable arsenic concentration showed significant increase of CyclinA substantiating the clinical data. An associated increase in S phase population of cells in cell cycle, indicative of enhanced proliferation was also noticed. On further investigation of the pathway to arsenic-induced proliferation, we observed that arsenic resulted: ROS generation; activated Erk signaling; stimulated AP-1 activity, including immediate early genes, c-Jun and c-Fos. N-Acetyl-l-cysteine, a ROS quencher, blocked the arsenic-induced effects. Our study underlines a previously undefined mechanism by which arsenic imparts its toxicity and results in uncontrolled cell proliferation.
 ...
PMID:Arsenic-induced cell proliferation is associated with enhanced ROS generation, Erk signaling and CyclinA expression. 2065 5