Inhibition of Interleukin-12 p40 Transcription and NF-κB Activation by Nitric Oxide in Murine Macrophages and Dendritic Cells

Xiong, Huabao; Zhu, Chen; Li, Fengling; Hegazi, Refaat; He, Kai-Li; Babyatsky, Mark W.; Bauer, Anthony J.; Plevy, Scott E.

doi:10.1074/jbc.m313416200

Cited by 104 publications

(111 citation statements)

References 36 publications

(37 reference statements)

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“…To the best of our knowledge, no previous studies have described the effect of the TNF-␣/IL-6 balance on regulating inflammatory and immune responses, but TNF-␣ is reported to be required for differentiation and maturation of classical APC and NO production by macrophages, which are important effectors in regulating innate immunity and adaptive immunity (50,51). TNF-␣ also initiates the polarization of naive T lymphocytes to the Th1 phenotype (52).…”

Section: Discussionmentioning

confidence: 99%

A Regulatory Effect of the Balance between TNF-α and IL-6 in the Granulomatous and Inflammatory Response to Rhodococcus aurantiacus Infection in Mice

Yimin

Kohanawa

2006

The Journal of Immunology

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After i.v. inoculation with Rhodococcus aurantiacus, wild-type (WT) mice develop nonnecrotic, epithelioid granulomas. Because a high level of TNF-α is observed during the initial phase postinfection, we examined the extent to which TNF-α contributes to granulomatous inflammation using TNF-α gene-deficient (TNF-α−/−) mice. Despite a lack of R. aurantiacus proliferation, TNF-α−/− mice displayed high mortality rates within 5 days postinfection, as well as a high level of IL-6 in their spleens. Histological examination showed an absence of granuloma formation in TNF-α−/− mice. Pretreatment of TNF-α−/− mice with rTNF-α failed to restore this granuloma formation but accelerated bacterial removal and cellular recruitment. This rTNF-α administration also attenuated IL-6 production, resulting in increased survival rates of TNF-α−/− mice. Heat-killed R. aurantiacus induced in vitro enhanced mRNA expression and production of IL-6 in macrophages and DCs from TNF-α−/− mice when compared with WT controls, and treatment of TNF-α−/− mouse cells with rTNF-α decreased the IL-6 secretion. Moreover, anti-TNF-α or anti-IL-6 treatment increased IL-6 or TNF-α production by WT mouse cells, respectively. These data suggest that the production of TNF-α and IL-6 can be negatively regulated by each other. Administration of rIFN-γ to TNF-α−/− mice caused immature granulomas in livers, and treatment with both rTNF-α and rIFN-γ led to the formation of mature granulomas. Overall, TNF-α appears crucial for bacterial clearance, cellular recruitment, and granuloma formation. The balance between TNF-α and IL-6 during the early phase of infection controls the development of the inflammatory response to R. aurantiacus infection.

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Section: Discussionmentioning

confidence: 99%

A Regulatory Effect of the Balance between TNF-α and IL-6 in the Granulomatous and Inflammatory Response to Rhodococcus aurantiacus Infection in Mice

Yimin

Kohanawa

2006

The Journal of Immunology

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“…Other catechins had little or no effect at the concentrations tested. Since it is reported that EGCG inhibits LPS-induced TNFa production and NO production in mouse macrophages, 11,28) we examined effect of catechins on TNFa and NO production induced by LPS. Similar to their effect on IL-12p40 production, (Ϫ)-ECG, (Ϫ)-EGCG and (Ϫ)-GCG decreased TNFa production significantly (Fig.…”

Section: Effect Of Catechins On Il-12p40mentioning

confidence: 99%

Effect of Various Catechins on the IL-12p40 Production by Murine Peritoneal Macrophages and a Macrophage Cell Line, J774.1

Ichikawa¹,

Matsui²,

Imai³

et al. 2004

Biological & Pharmaceutical Bulletin

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“…Protein concentration was determined using the Bradford assay (Pierce). Western blot analyses were performed on nuclear extracts as described previously (16). Anti-p65 and anti-c-Rel Abs were obtained from Santa Cruz Biotechnology, and antipoly(ADP-ribose) and anti-phosphorylated (phospho) p65 Abs were obtained from Cell Signaling.…”

Section: Nuclear Extracts and Western Blottingmentioning

confidence: 99%

Amelioration of Chronic Murine Colitis by Peptide-Mediated Transduction of the IκB Kinase Inhibitor NEMO Binding Domain Peptide

Davé¹,

Tilstra²,

Matsuoka³

et al. 2007

The Journal of Immunology

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The NF-κB family of transcription factors is a central regulator of chronic inflammation. The phosphorylation of IκB proteins by the IκB kinase (IKK) complex (IKKα, IKKβ, and NF-κB essential modulator or NEMO) is a key step in NF-κB activation. Peptides corresponding to the NEMO binding domain (NBD) of IKK blocks NF-κB activation without inhibiting basal NF-κB activity. In this report, we determined the effects of the IKK inhibitor peptide (NBD) in a model of spontaneously occurring chronic murine colitis, the IL-10-deficient (IL-10−/−) mouse. Using a novel cationic peptide transduction domain (PTD) consisting of eight lysine residues (8K), we were able to transduce the NBD peptide into cells and tissues. In a NF-κB reporter system, 8K-NBD dose-dependently inhibits TNF-induced NF-κB activation. Furthermore, 8K-NBD inhibited nuclear translocation of NF-κB family members. In NF-κBEGFP knock-in mice, 8K-NBD inhibited LPS-activated NF-κB (EGFP activity) in the ileum but did not inhibit basal NF-κB in Peyer’s patches. IL-10−/− mice treated systemically with 8K-NBD demonstrate amelioration of established colitis, decreased NF-κB activation in the lamina propria, and a reduction in spontaneous intestinal IL-12 p40, TNF, IFN-γ, and IL-17 production. These results demonstrate that inhibitors of IKK, in particular a PTD-NBD peptide, may be therapeutic in the treatment of inflammatory bowel disease.

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Inhibition of Interleukin-12 p40 Transcription and NF-κB Activation by Nitric Oxide in Murine Macrophages and Dendritic Cells

Cited by 104 publications

References 36 publications

A Regulatory Effect of the Balance between TNF-α and IL-6 in the Granulomatous and Inflammatory Response to Rhodococcus aurantiacus Infection in Mice

A Regulatory Effect of the Balance between TNF-α and IL-6 in the Granulomatous and Inflammatory Response to Rhodococcus aurantiacus Infection in Mice

Effect of Various Catechins on the IL-12p40 Production by Murine Peritoneal Macrophages and a Macrophage Cell Line, J774.1

Amelioration of Chronic Murine Colitis by Peptide-Mediated Transduction of the IκB Kinase Inhibitor NEMO Binding Domain Peptide

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