Anti-inflammatory properties of extracts from plants of the Rubiaceae family

Minocycline protects against asthma independently of its antibiotic function and was recently reported as a potent poly(ADP-ribose) polymerase (PARP) inhibitor. In an animal model of asthma, a single administration of minocycline conferred excellent protection against ovalbumin-induced airway eosinophilia, mucus hypersecretion, and Th2 cytokine production (IL-4/IL-5/IL-12(p70)/IL-13/GM-CSF) and a partial protection against airway hyperresponsiveness. These effects correlated with pronounced reduction in lung and sera allergen-specific IgE. A reduction in poly(ADP-ribose) immunoreactivity in the lungs of minocycline-treated/ovalbumin-challenged mice correlated with decreased oxidative DNA damage. The effect of minocycline on PARP may be indirect, as the drug failed to efficiently block direct PARP activation in lungs of N-methyl-N'-nitro-N-nitroso-guanidine-treated mice or H(2)O(2)-treated cells. Minocycline blocked allergen-specific IgE production in B cells potentially by modulating T cell receptor (TCR)-linked IL-4 production at the mRNA level but not through a modulation of the IL-4-JAK-STAT-6 axis, IL-2 production, or NFAT1 activation. Restoration of IL-4, ex vivo, rescued IgE production by minocycline-treated/ovalbumin-stimulated B cells. IL-4 blockade correlated with a preferential inhibition of the NF-κB activation arm of TCR but not GSK3, Src, p38 MAPK, or ERK1/2. Interestingly, the drug promoted a slightly higher Src and ERK1/2 phosphorylation. Inhibition of NF-κB was linked to a complete blockade of TCR-stimulated GATA-3 expression, a pivotal transcription factor for IL-4 expression. Minocycline also reduced TNF-α-mediated NF-κB activation and expression of dependent genes. These results show a potentially broad effect of minocycline but that it may block IgE production in part by modulating TCR function, particularly by inhibiting the signaling pathway, leading to NF-κB activation, GATA-3 expression, and subsequent IL-4 production.

Diarrhea during the Conditioning Regimen Is Correlated with the Occurrence of Severe Acute Graft-versus-Host Disease through Systemic Release of Inflammatory Cytokines

3-Formylchromone (3-FC) has been associated with anticancer potential through a mechanism yet to be elucidated. Because of the critical role of NF-κB in tumorigenesis, we investigated the effect of this agent on the NF-κB activation pathway. Whether activated by inflammatory agents (such as TNF-α and endotoxin) or tumor promoters (such as phorbol ester and okadaic acid), 3-FC suppressed NF-κB activation. It also inhibited constitutive NF-κB expressed by most tumor cells. This activity correlated with sequential inhibition of IκBα kinase (IKK) activation, IκBα phosphorylation, IκBα degradation, p65 phosphorylation, p65 nuclear translocation, and reporter gene expression. We found that 3-FC inhibited the direct binding of p65 to DNA, and this binding was reversed by a reducing agent, thus suggesting a role for the cysteine residue. Furthermore, mutation of Cys38 to Ser in p65 abolished this effect of the chromone. This result was confirmed by a docking study. 3-FC also inhibited IKK activation directly, and the reducing agent reversed this inhibition. Furthermore, mutation of Cys179 to Ala in IKK abolished the effect of the chromone. Suppression of NF-κB activation led to inhibition of anti-apoptotic (Bcl-2, Bcl-xL, survivin, and cIAP-1), proliferative (cyclin D1 and COX-2), invasive (MMP-9 and ICAM-1), and angiogenic (VEGF) gene products and sensitization of tumor cells to cytokines. Thus, this study shows that modification of cysteine residues in IKK and p65 by 3-FC leads to inhibition of the NF-κB activation pathway, suppression of anti-apoptotic gene products, and potentiation of apoptosis in tumor cells.

Publication bias: Graphical and statistical methods

Immune Activation in Patients With Irritable Bowel Syndrome

Role of Blood- and Tissue-Associated Inducible Nitric-Oxide Synthase in Colonic Inflammation

Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells

α-MSH-Stimulated Tolerogenic Dendritic Cells Induce Functional Regulatory T Cells and Ameliorate Ongoing Skin Inflammation

Bortezomib-resistant nuclear factor κB expression in stem-like cells in mantle cell lymphoma

Aim: The present study elucidated the expression level of Nrf2 and NF-κB, in chronic kidney disease (CKD) patients from South India. Further, the expression levels of these genes are analyzed for cytokines TNF-α and IFN-γ and various subgroups of cases including dialysis, non-dialysis, diabetic and non-diabetic CKD patients, and correlation analysis performed. Methods: 133 CKD patients and 133 healthy individuals were enrolled for the evaluation of NF-κB and Nrf2 expression by qPCR. Results: Upregulated Nrf2 mRNA expression (as fold change) was observed in diabetic (Fc: 1.13), and non-diabetic (Fc: 1.30) patients. Inversely, Nrf2 mRNA expression was down regulated in non-dialysis groups (Fc: 0.80). NF-κB expression was significantly upregulated in non-diabetic (Fc:1.92), non-dialysis (Fc:1.59), dialysis (Fc: 1.36) and CKD patients (pooled) (Fc: 1.27). A dysregulated NF-κB expression was observed in diabetic groups (Fc: 0.69). Nrf2 mRNA expression were positively correlated with IFN-γ expression in diabetes (r = 0.28, p = 0.05) and non-diabetic CKD patients (r = 0.37, p < 0.002). Likewise, TNF-α expression was positively correlated with Nrf2 expression in CKD (pooled) patients (r = 0.33, p < 0.000). A negative correlation was observed in Nrf2 and NF-κB expression in CKD (pooled) (r = -0.028, p = 0.833). Conclusion: The study concluded the down regulated Nrf2 and upregulated NF-κB expressions in non-dialysis patients. On the contrary, in diabetic CKD patients, the expression level of NF-κB was downregulated and Nrf2 was upregulated. Thus, a negative correlation was observed between Nrf2 and NF-κB genes with respect to their expression patterns.

Aim: The present study elucidated the expression level of Nrf2 and NF-κB, in chronic kidney disease (CKD) patients from South India. Further, the expression levels of these genes are analyzed for cytokines TNF-α and IFN-γ and various subgroups of cases including dialysis, non-dialysis, diabetic and non-diabetic CKD patients, and correlation analysis performed. Methods: 133 CKD patients and 133 healthy individuals were enrolled for the evaluation of NF-κB and Nrf2 expression by qPCR. Results: Upregulated Nrf2 mRNA expression (as fold change) was observed in diabetic (Fc: 1.13), and non-diabetic (Fc: 1.30) patients. Inversely, Nrf2 mRNA expression was down regulated in non-dialysis groups (Fc: 0.80). NF-κB expression was significantly upregulated in non-diabetic (Fc:1.92), non-dialysis (Fc:1.59), dialysis (Fc: 1.36) and CKD patients (pooled) (Fc: 1.27). A dysregulated NF-κB expression was observed in diabetic groups (Fc: 0.69). Nrf2 mRNA expression were positively correlated with IFN-γ expression in diabetes (r = 0.28, p = 0.05) and non-diabetic CKD patients (r = 0.37, p < 0.002). Likewise, TNF-α expression was positively correlated with Nrf2 expression in CKD (pooled) patients (r = 0.33, p < 0.000). A negative correlation was observed in Nrf2 and NF-κB expression in CKD (pooled) (r = -0.028, p = 0.833). Conclusion: The study concluded the down regulated Nrf2 and upregulated NF-κB expressions in non-dialysis patients. On the contrary, in diabetic CKD patients, the expression level of NF-κB was downregulated and Nrf2 was upregulated. Thus, a negative correlation was observed between Nrf2 and NF-κB genes with respect to their expression patterns.

The Vagus Nerve: A Tonic Inhibitory Influence Associated With Inflammatory Bowel Disease in a Murine Model

α5β1 Integrin Blockade Inhibits Lymphangiogenesis in Airway Inflammation

Manipulation of the Microbiota for Treatment of IBS and IBD—Challenges and Controversies

Detrimental Effect of the Proteasome Inhibitor, Bortezomib in Bacterial Superantigen- and Lipopolysaccharide-induced Systemic Inflammation