Simvastatin inhibits pro-inflammatory mediators through induction of heme oxygenase-1 expression in lipopolysaccharide-stimulated RAW264.7 macrophages

Leung, Pak-On; Wang, Sue-Hong; Lu, Sheng-Hua; Chou, Wen-Hsiang; Shiau, Chia‐Yang; Chou, Tz-Chong

doi:10.1016/j.toxlet.2011.09.004

Cited by 29 publications

(22 citation statements)

References 25 publications

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“…The HO-1 activity was determined by measuring the bilirubin formation as previously described [20]. Briefly, the cell pellet of various groups was suspended in potassium phosphate buffer (100 mM, pH 7.4) followed by sonication in ice before centrifugation at 18,000 × g for 10 min at 4°C.…”

Section: Ho-1 Activity Assaymentioning

confidence: 99%

Activation of Nrf2/HO-1signaling pathway involves the anti-inflammatory activity of magnolol in Porphyromonas gingivalis lipopolysaccharide-stimulated mouse RAW 264.7 macrophages

Lü

Hsu

Chen

et al. 2015

International Immunopharmacology

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Section: Ho-1 Activity Assaymentioning

confidence: 99%

Activation of Nrf2/HO-1signaling pathway involves the anti-inflammatory activity of magnolol in Porphyromonas gingivalis lipopolysaccharide-stimulated mouse RAW 264.7 macrophages

Lü

Hsu

Chen

et al. 2015

International Immunopharmacology

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“…Statins, however, also possess secondary anti-inflammatory properties which are achieved via (i) interference with G-protein receptor-mediated signaling mechanisms in immune and inflammatory cells [68] and (ii) induction of the enzyme heme oxygenase-1 which, in turn, mediates the synthesis of anti-inflammatory proteins [69]. Both mechanisms have the potential to control harmful neutrophilic inflammation.…”

Section: Adjuvant Anti-inflammatory Strategies In Severe Pneumococcalmentioning

confidence: 99%

Recent advances in our understanding of Streptococcus pneumoniae infection

Feldman

2014

F1000Prime Rep

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A number of significant challenges remain with regard to the diagnosis, treatment, and prevention of infections with Streptococcus pneumoniae (pneumococcus), which remains the most common bacterial cause of community-acquired pneumonia. Although this infection is documented to be extremely common in younger children and in older adults, the burden of pneumonia it causes is considerably underestimated, since the incidence statistics are derived largely from bacteremic infections, because they are easy to document, and yet the greater burden of pneumococcal pneumonias is non-invasive. It has been estimated that for every bacteremic pneumonia that is documented, three non-bacteremic infections occur. Management of these infections is potentially complicated by the increasing resistance of the isolates to the commonly used antibiotics. Furthermore, it is well recognized that despite advances in medical care, the mortality of bacteremic pneumococcal pneumonia has remained largely unchanged over the past 50 years and averages approximately 12%. Much recent research interest in the field of pneumococcal infections has focused on important virulence factors of the organism, on improved diagnostic and prognostication tools, on defining risk factors for death, on optimal treatment strategies involving both antibiotics and adjunctive therapies, and on disease prevention. It is hoped that through these endeavors the outlook of pneumococcal infections will be improved.

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“…Statins have been widely prescribed to reduce cholesterol levels by inhibiting HMG-CoA reductase [301]. However, in vitro and in vivo rodent models have shown that statins can robustly induce HO-1 in monocytes/macrophages, leading to reduction of inflammation [302-305]. BBB-permeable statins therefore have the potential to induce HO-1 in cells of the CNS, including macrophages, microglia, and astrocytes, although such studies have yet to be reported.…”

Section: Therapeutic Potential Of Exogenous Inducers Of Heme Oxygenasmentioning

confidence: 99%

Heme Oxygenase-1 Dysregulation in the Brain: Implications for HIVAssociated Neurocognitive Disorders

Ambegaokar¹,

Kolson

2014

CHR

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Heme oxygenase-1 (HO-1) is a highly inducible and ubiquitous cellular enzyme that subserves cytoprotective responses to toxic insults, including inflammation and oxidative stress. In neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis, HO-1 expression is increased, presumably reflecting an endogenous neuroprotective response against ongoing cellular injury. In contrast, we have found that in human immunodeficiency virus (HIV) infection of the brain, which is also associated with inflammation, oxidative stress and neurodegeneration, HO-1 expression is decreased, likely reflecting a unique role for HO-1 deficiency in neurodegeneration pathways activated by HIV infection. We have also shown that HO-1 expression is significantly suppressed by HIV replication in cultured macrophages which represent the primary cellular reservoir for HIV in the brain. HO-1 deficiency is associated with release of neurotoxic levels of glutamate from both HIV-infected and immune-activated macrophages; this glutamate-mediated neurotoxicity is suppressed by pharmacological induction of HO-1 expression in the macrophages. Thus, HO-1 induction could be a therapeutic strategy for neuroprotection against HIV infection and other neuroinflammatory brain diseases. Here, we review various stimuli and signaling pathways regulating HO-1 expression in macrophages, which could promote neuronal survival through HO-1-modulation of endogenous antioxidant and immune modulatory pathways, thus limiting the oxidative stress that can promote HIV disease progression in the CNS. The use of pharmacological inducers of endogenous HO-1 expression as potential adjunctive neuroprotective therapeutics in HIV infection is also discussed.

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Simvastatin inhibits pro-inflammatory mediators through induction of heme oxygenase-1 expression in lipopolysaccharide-stimulated RAW264.7 macrophages

Cited by 29 publications

References 25 publications

Activation of Nrf2/HO-1signaling pathway involves the anti-inflammatory activity of magnolol in Porphyromonas gingivalis lipopolysaccharide-stimulated mouse RAW 264.7 macrophages

Activation of Nrf2/HO-1signaling pathway involves the anti-inflammatory activity of magnolol in Porphyromonas gingivalis lipopolysaccharide-stimulated mouse RAW 264.7 macrophages

Recent advances in our understanding of Streptococcus pneumoniae infection

Heme Oxygenase-1 Dysregulation in the Brain: Implications for HIVAssociated Neurocognitive Disorders

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