MH2 domain of Smad3 reduces HIV-1 Tat-induction of cytokine secretion

Eldeen, Mazen B.; Deshmane, Satish L.; Simbiri, Kenneth O; Khalili, Kamel; Amini, Shohreh; Sawaya, Bassel E.

doi:10.1016/j.jneuroim.2006.04.004

Cited by 11 publications

(7 citation statements)

References 43 publications

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“…As CCL2 is associated with a variety of disorders, several regulatory factors have been found to affect its production, such as enhancers AP-1, AP-2beta, STAT6, NFκB [49-51], TNF-α [52], Tat [53], LPS [54], S1P [55], and Nef [56]. There are also a numbers of suppressors, such as RS102895 [57], p38 or SB203580 [58], HDL [38], and Smad3 [59]. In one study, p53 was found to be involved in the regulation of CCL2 production in HPV-positive cells [60].…”

Section: Discussionmentioning

confidence: 99%

p53 is an Important Regulator of CCL2 Gene Expression

Tang¹,

Asano²,

O’Reilly³

et al. 2012

CMM

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The p53 protein is a sequence-specific DNA-binding factor that regulates inflammatory genes such as CCL2/MCP-1 that may play a role in various diseases. A recent study has indicated that the knockdown of human p53 leads to a strong negative regulation of CCL2 induction. We are therefore interested in how p53 regulates CCL2 gene expression. In the following study, our findings indicate that UV-induced p53 accumulation in mouse macrophages significantly decreases LPS-induced CCL2 production, and that p53 binds to CCL2 5’UTR in the region (16-35). We also found that a p53 domain (p53pep170) mimics full length p53 to down-regulate CCL2 promoter activity. Treatment of p53-deficient mouse primary macrophages with synthetic p53pep170 was found to decrease LPS-induced production of CCL2 without association with cellular endogenous p53. CCL2 production induced by lentiCLG in human monocytes or mouse primary macrophages was blocked in the presence of p53pep170. Overall, these results demonstrate that p53 or its derived peptide (p53pep170) is an important regulator of CCL2 gene expression via its binding activity, and acts as a novel model for future studies linking p53 and its short peptide to pave the way to possible pharmaceutical intervention of CCL2-mediated inflammatory and cancer diseases.

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Section: Discussionmentioning

confidence: 99%

p53 is an Important Regulator of CCL2 Gene Expression

Tang¹,

Asano²,

O’Reilly³

et al. 2012

CMM

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“…CNS production of proinflammatory cytokines, chemokines and neurotoxic viral gene products may lead to extensive brain injury 44. MCP‐1 may influence viral replication within the brain 45, which occurs primarily in cells of monocytic lineage (monocyte‐derived macrophages and microglia), alter the inflammatory cascade 46 or otherwise interact with viral proteins 38, 47–52. Experimental evidence suggests that MCP‐1 primes the responsiveness of glia to inflammatory stimuli 53 and an MCP‐1 antagonist delays onset and reduces neurological signs associated with neuroinflammation 54.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of neurological status in HIV infection: A 3‐year study

Ragin

Ochs

et al. 2010

Proteomics Clinical Apps

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In this investigation, circulating cytokines and chemokines were screened as correlates of brain injury in individuals with advanced Human Immunodeficiency Virus (HIV) infection. Markers were quantified using high throughput multiplexed analysis at baseline and three years later in the clinical course. Neurological status was ascertained based on objective measurements of the brain derived in vivo with Magnetic Resonance (MR) segmentation algorithms and with Diffusion Tensor Imaging (DTI). Of the markers examined, Monocyte Chemoattractant Protein-1 (n.b. MCP-1 or CCL-2) was the most prominent correlate of brain injury. At the initial assessment, elevated MCP-1 levels correlated with alterations in brain white matter. The relationship to brain injury was more extensive three years later; MCP-1 was significantly correlated with both microstructural measures (fractional anisotropy and mean diffusivity) and with brain atrophy (in gray matter and overall parenchyma). Conclusion These findings provide further evidence of the potential importance of MCP-1 as a marker of neurological injury in HIV infection. These observations build on our prior descriptions suggesting that elevated levels of MCP-1 may be a useful predictive marker for HIV-associated neurocognitive disorder (HAND). As a potent chemoattractant, MCP-1 may mediate injury through participation in self-reinforcing cycles of chronic immune activation and cytokine/chemokine-mediated neurotoxicity.

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“…Adeno-Vpr recombinant shuttle containing Vpr sequence (pDC515-Vpr) was transfected into HEK-293 cells with pBHGfrt (del) E1, 3FLP, and a plasmid that provides adenovirus type 5 genome deleted in E1 and E3 genes. Plaques of recombinant adenovirus arising as a result of frt/FLP recombination were isolated, grown, and purified by cesium chloride density equilibrium banding as described previously (35). Empty shuttle plasmid, pDC515, was used to construct control adenoviral vector (Adeno-null, a virus without a transgene).…”

Section: Methodsmentioning

confidence: 99%