Propionibacterium acnes-induced iNOS and COX-2 protein expression via ROS-dependent NF-κB and AP-1 activation in macrophages

Tsai, Hsiou Hsin; Lee, William R.; Wang, Pai Hua; Cheng, Kur Ta; Chen, Yen Chou; Shen, Shing Chuan

doi:10.1016/j.jdermsci.2012.10.009

Cited by 73 publications

(52 citation statements)

References 34 publications

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“…Modulation of iNOS expression by ROS is not without precedent. High-MOI infection of macrophages with Propionibacterium acnes increases ROS levels, which in turn upregulate iNOS via NF-B/AP-1 activation (58). Similar dependence on ROS for nitric oxide production has also been observed in mouse endothelial cells stimulated with IFN-␥ and LPS (59).…”

Section: Discussionsupporting

confidence: 54%

Chlamydia muridarum Infection of Macrophages Elicits Bactericidal Nitric Oxide Production via Reactive Oxygen Species and Cathepsin B

Rajaram

Nelson

2015

Infect Immun

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bThe ability of certain species of Chlamydia to inhibit the biogenesis of phagolysosomes permits their survival and replication within macrophages. The survival of macrophage-adapted chlamydiae correlates with the multiplicity of infection (MOI), and optimal chlamydial growth occurs in macrophages infected at an MOI of <1. In this study, we examined the replicative capacity of Chlamydia muridarum in the RAW 264.7 murine macrophage cell line at different MOIs. C. muridarum productively infected these macrophages at low MOIs but yielded few viable elementary bodies (EBs) when macrophages were infected at a moderate (10) or high (100) MOI. While high MOIs caused cytotoxicity and irreversible host cell death, macrophages infected at a moderate MOI did not show signs of cytotoxicity until late in the infectious cycle. Inhibition of host protein synthesis rescued C. muridarum in macrophages infected at a moderate MOI, implying that chlamydial growth was blocked by activated defense mechanisms. Conditioned medium from these macrophages was antichlamydial and contained elevated levels of interleukin 1␤ (IL-1␤), IL-6, IL-10, and beta interferon (IFN-␤). Macrophage activation depended on Toll-like receptor 2 (TLR2) signaling, and cytokine production required live, transcriptionally active chlamydiae. A hydroxyl radical scavenger and inhibitors of inducible nitric oxide synthase (iNOS) and cathepsin B also reversed chlamydial killing. High levels of reactive oxygen species (ROS) led to an increase in cathepsin B activity, and pharmacological inhibition of ROS and cathepsin B reduced iNOS expression. Our data demonstrate that MOI-dependent TLR2 activation of macrophages results in iNOS induction via a novel ROS-and cathepsindependent mechanism to facilitate C. muridarum clearance. Infection of host epithelial cells by Chlamydia spp. sets in motion a cascade of signaling events that recruit multiple innate immune effectors to the infected site. Upon recognition of chlamydial pathogen-associated molecular patterns (PAMPs) and host danger signals, infiltrating leukocytes undergo transcriptional reprogramming to amplify the immune response by producing several cytokines and antimicrobial factors. The subsequent inflammatory process aids in bacterial clearance and primes elements of adaptive immunity while also contributing to the damaging pathology associated with chlamydial disease (1, 2).Cells of the monocyte-macrophage lineage play critical roles in innate and adaptive immunity against chlamydial infections. Depletion of macrophages from mice prior to infection with Chlamydia muridarum and Chlamydia psittaci results in increased morbidity and pathogen burden (3, 4). Adoptive transfer of macrophages to RAG-1 Ϫ/Ϫ /gamma interferon (IFN-␥) Ϫ/Ϫ mice has been shown to be sufficient for the control of Chlamydia pneumoniae in lung models of infection (5). Chlamydia trachomatis is rapidly rerouted to lysosomes in RAW macrophages, where the pathogen is killed (6). Macrophage killing and subsequent presentation of elementary body (EB)...

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Section: Discussionsupporting

confidence: 54%

Chlamydia muridarum Infection of Macrophages Elicits Bactericidal Nitric Oxide Production via Reactive Oxygen Species and Cathepsin B

Rajaram

Nelson

2015

Infect Immun

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“…ROS are inevitably produced via the oxygen-using metabolic process [23]. Previous studies have demonstrated that keratinocytes and macrophages generate many ROS with P. acnes stimulation [17]. When we cocultured NPCs with P. acnes , the concentration of ROS significantly increased, along with an increase of iNOS/NO and COX-2/PGE 2 , whereas excessive iNOS/NO and COX-2/PGE 2 expressions were significantly decreased when ROS were neutralized by NAC (Figures 4(d)–4(f)), suggesting that ROS are the key molecules involved in P. acnes -facilitated iNOS/NO and COX-2/PGE 2 activation.…”

Section: Discussionmentioning

confidence: 99%

“…When stimulated, the activation of iNOS and COX-2 results in the production of NO and PGE 2 in IVDs and causes harmful pathophysiologic effects such as inflammation, apoptosis, and degeneration [13–16]. Interestingly, P. acnes is able to stimulate various cells, such as macrophages and keratinocytes, to produce NO and PGE 2 [17]. An important question, therefore, was whether P. acnes could promote the expression of NO and PGE 2 in IVDs and thus induce IVDD.…”

Section: Introductionmentioning

confidence: 99%

Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX‐2/PGE₂ Activation via the ROS‐Dependent NF‐κB Pathway

Yan

Tang

Jiao

et al. 2018

Oxidative Medicine and Cellular Longevity

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Accumulating evidence suggests that Propionibacterium acnes (P. acnes) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD). However, the underlying mechanisms by which P. acnes induces IVDD have been unclear. In this study, we quantified the severity of IVDD, as well as the expressions of inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and cyclooxygenase (COX-2)/prostaglandin (PGE2) in human intervertebral discs (IVDs) infected with P. acnes. Compared with P. acnes-negative IVDs, P. acnes-positive IVDs showed increased iNOS/NO and COX-2/PGE2 activity concomitant with more severe IVDD. In order to detect the potential correlation between iNOS/NO expression, COX-2/PGE2 expression, and IVDD, we developed a P. acnes-induced IVDD rat model and found that the upregulation of iNOS/NO and COX-2/PGE2 was essential to the occurrence of P. acnes-induced IVDD. This finding was supported by the fact that the inhibition of iNOS/NO and COX-2/PGE2 activity ameliorated IVDD significantly, as evidenced by restored aggrecan and collagen II expression both in vivo and in vitro. Mechanistically, we found that P. acnes induced iNOS/NO and COX-2/PGE2 expressions via a reactive oxygen species- (ROS-) dependent NF-κB cascade. Furthermore, NADPH oxidase participated in P. acnes-induced ROS, iNOS/NO, and COX-2/PGE2 expressions. Overall, these findings further validated the involvement of P. acnes in the pathology of IVDD and provided evidence that P. acnes-induced iNOS/NO and COX-2/PGE2 activation via the ROS-dependent NF-κB pathway is likely responsible for the pathology of IVDD.

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“…5A, the activation of ERK, JNK, and p38 via LPS stimulation in RAW264.7 macrophages was inhibited by DDP treatment in a dose-dependent manner, without a change in total protein expression. LPS-induced MAPK activation results in enhanced production of Jun and Fos, followed by the exertion of Jun and Fos transcriptional effects on the AP-1 consensus sequence(s) in the promoter regions of target genes [9,10,18]. We sought to determine the inhibitory effects of DDP on the nuclear translocation of AP-1, c-fos and c-jun, in LPS-stimulated RAW264.7 cells.…”

Section: Ddp Inhibits Mapk and Ap-1 Activationmentioning

confidence: 99%

(E)-3-(3,4-dihydroxy-2-methoxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one, a novel licochalcone B derivative compound, suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice

Park

Jun

Kim

2014

Chemico-Biological Interactions

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Propionibacterium acnes-induced iNOS and COX-2 protein expression via ROS-dependent NF-κB and AP-1 activation in macrophages

Cited by 73 publications

References 34 publications

Chlamydia muridarum Infection of Macrophages Elicits Bactericidal Nitric Oxide Production via Reactive Oxygen Species and Cathepsin B

Chlamydia muridarum Infection of Macrophages Elicits Bactericidal Nitric Oxide Production via Reactive Oxygen Species and Cathepsin B

Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX‐2/PGE₂ Activation via the ROS‐Dependent NF‐κB Pathway

(E)-3-(3,4-dihydroxy-2-methoxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one, a novel licochalcone B derivative compound, suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice

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Propionibacterium acnes-induced iNOS and COX-2 protein expression via ROS-dependent NF-κB and AP-1 activation in macrophages

Cited by 73 publications

References 34 publications

Chlamydia muridarum Infection of Macrophages Elicits Bactericidal Nitric Oxide Production via Reactive Oxygen Species and Cathepsin B

Chlamydia muridarum Infection of Macrophages Elicits Bactericidal Nitric Oxide Production via Reactive Oxygen Species and Cathepsin B

Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX‐2/PGE2 Activation via the ROS‐Dependent NF‐κB Pathway

(E)-3-(3,4-dihydroxy-2-methoxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one, a novel licochalcone B derivative compound, suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice

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Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX‐2/PGE₂ Activation via the ROS‐Dependent NF‐κB Pathway