Modulation of LPS stimulated NF-kappaB mediated Nitric Oxide production by PKCε and JAK2 in RAW macrophages

Jones, Edward G.; Adcock, Ian M.; Ahmed, Bayes; Punchard, Neville A.

doi:10.1186/1476-9255-4-23

Cited by 96 publications

(67 citation statements)

References 45 publications

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“…Moreover, it has been shown that ERK inhibitor potentiates the binding of NFκB and consequently its pro-inflammatory effect [24]. Other studies have reached the same conclusion; Jones et al, [25] shows that PMA (phorbol-12-myristate-13-acetate), which is known to activate ERK pathway, significantly attenuated LPS-induced NO production in RAW264.7 cells. Another group demonstrated that hyper activation of the ERK pathway contributes to the negative regulation of LPS-induced IL-12 p40 production in mouse peritoneal macrophages [26].…”

Section: Discussionsupporting

confidence: 62%

N-methyl pyrrolidone (NMP) inhibits lipopolysaccharide-induced inflammation by suppressing NF-κB signaling

et al. 2015

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OBJECTIVE: N-methyl pyrrolidone (NMP), a small bioactive molecule, stimulates bone formation and inhibits osteoclast differentiation and bone resorption. The present study was aimed to evaluate the anti-inflammatory potentials of NMP on the inflammatory process and the underlying molecular mechanisms in RAW264.7 macrophages. MATERIALS AND METHODS: RAW264.7 macrophages and mouse primary bone marrow macrophages (mBMMs) were used as an in vitro model to investigate inflammatory processes. Cells were pre-treated with or without NMP and then stimulated with lipopolysaccharides (LPS). The productions of cytokines and NO were determined by proteome profiler method and nitrite analysis, respectively. The expressions of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were measured by Western blotting and/or qPCR. Western blot, ELISA-base reporter assay, and immunofluorescence were used to evaluate the activation of MAP kinases and NF-B. RESULTS: LPS-induced mRNA expressions of TNF-, IL-1, IL-6, iNOS, and COX-2 were inhibited by NMP in a dose-dependent manner. NMP also suppressed the LPS-increased productions of iNOS and NO. The proteome profiler array showed that several cytokines and chemokines involved in inflammation and up-regulated by LPS stimulation were significantly down-regulated by NMP. Additionally, this study shows that the effect of NMP is mediated through down-regulation of NFB pathway. CONCLUSIONS: Our results show that NMP inhibits the inflammatory mediators in macrophages by an NFB-dependent mechanism, based on the epigenetical activity of NMP as bromodomain inhibitor. In the light of its action on osteoblast and osteoclast differentiation process and its anti-inflammatory potential, NMP might be used in inflammation-related bone loss. CONCLUSIONS:Our results show that NMP inhibits the inflammatory mediators in macrophages by an NFκB-dependent mechanism, based on the epigenetical activity of NMP as bromodomain inhibitor. In the light of its action on osteoblast and osteoclast differentiation process and its anti-inflammatory potential, NMP might be used in inflammation-related bone loss.

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Section: Discussionsupporting

confidence: 62%

N-methyl pyrrolidone (NMP) inhibits lipopolysaccharide-induced inflammation by suppressing NF-κB signaling

et al. 2015

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“…In these present studies increases in glutamate release were 19 apparent in microglia, but not macrophages, after bacterial stimulation. Expression of inducible nitric oxide synthase will also be enhanced after microglial activation as was evident in these present studies.…”

Section: Discussionsupporting

confidence: 49%

“…Among the many inflammatory mediators produced by activated phagocytic cells, i.e. macrophages and microglia, NO production has been widely regarded as representative of inflammatory activation [19] [20]. Therefore inhibitors which, preferentially target molecules that are involved in NFkappaB activation may be of therapeutic value.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory actions of a taurine analogue, ethane β-sultam, in phagocytic cells, in vivo and in vitro

Ward

Lallemand

Witte

et al. 2011

Biochemical Pharmacology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64

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“…In our data, treatment with SN50, a NF-kB inhibitor, reduced LECT2-induced H. pylori killing and NO production in macrophages. Since NF-kB activation can stimulate iNOS, leading to enhanced NO production (Jones et al, 2007), our results may preliminarily indicate that NF-kB activation by LECT2 mediates NO production to enhance H. pylori killing by macrophages.…”

Section: Discussionmentioning

confidence: 83%

LECT2 association with macrophage-mediated killing of Helicobacter pylori by activating NF-κB and nitric oxide production

Shen

Chen

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Helicobacter pylori employs unique methods to colonize the stomach, which induces chronic inflammation. It is also able to avoid eradication by macrophages and other immune cells. Leukocyte cell-derived chemotaxin 2 (LECT2), a multi-functional cytokine involved in many pathological conditions, has recently been shown to activate macrophages via the CD209a receptor. Therefore, we aimed to investigate the effects of LECT2 on H. pylori-infected macrophages. Macrophages were treated with recombinant LECT2, and both their ability to kill H. pylori and produce nitric oxide were analyzed. Western blot was performed to determine nuclear translocation and protein phosphorylation of p65, a subunit of nuclear factor (NF)-kB. Transfection experiments were performed to analyze the signaling pathway of LECT2 in macrophages. We found that treatment with LECT2 enhanced H. pylori killing and nitric oxide production in macrophages. In addition, DNA-binding activity and nuclear translocation of p65 were up-regulated by LECT2 treatment. Furthermore, we found that NFkB activation by LECT2 was mediated by Raf-1 in macrophages, and Raf-1 phosphorylation was specifically altered in response to LECT2. Moreover, LECT2 induced Ser28 phosphorylation in the intracellular domain of CD209a. CD209a Ser28 phosphorylation was required for LECT2-induced Raf-1 and NF-kB activation in RAW264.7 macrophages. Our study showed that the effects of LECT2 on H. pylori killing and nitric oxide production were dependent on CD209a phosphorylation, Raf-1, and NF-kB activation. Together, these results demonstrate for the first time that exposure to LECT2 can modulate specific intracellular mechanisms downstream of CD209a to enhance H. pylori killing and nitric oxide production in macrophages.

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Modulation of LPS stimulated NF-kappaB mediated Nitric Oxide production by PKCε and JAK2 in RAW macrophages

Cited by 96 publications

References 45 publications

N-methyl pyrrolidone (NMP) inhibits lipopolysaccharide-induced inflammation by suppressing NF-κB signaling

N-methyl pyrrolidone (NMP) inhibits lipopolysaccharide-induced inflammation by suppressing NF-κB signaling

Anti-inflammatory actions of a taurine analogue, ethane β-sultam, in phagocytic cells, in vivo and in vitro

LECT2 association with macrophage-mediated killing of Helicobacter pylori by activating NF-κB and nitric oxide production

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