Naringenin suppresses the production of thymic stromal lymphopoietin through the blockade of RIP2 and caspase-1 signal cascade in mast cells

Moon, Phil‐Dong; Choi, In-Hwa; Kim, Hyung-Min

doi:10.1016/j.ejphar.2011.09.163

Cited by 50 publications

(33 citation statements)

References 26 publications

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“…(22). In line with this, suppression of Rip2 expression using Rip2 siRNA resulted in abrogation of NF-kB activation (23) and reduction of TSLP and IL-1b expression in mast cells (24,25).…”

Section: Discussionmentioning

confidence: 70%

Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

Goh

Cook

Upton

et al. 2013

The Journal of Immunology

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Persistent activation of NF-κB has been associated with the development of asthma. Receptor-interacting protein 2 (Rip2) is a transcriptional product of NF-κB activation. It is an adaptor protein with serine/threonine kinase activity and has been shown to positively regulate NF-κB activity. We investigated potential protective effects of Rip2 gene silencing using small interfering RNA (siRNA) in an OVA-induced mouse asthma model. Rip2 protein level was found to be upregulated in allergic airway inflammation. A potent and selective Rip2 siRNA given intratracheally knocked down Rip2 expression in OVA-challenged lungs and reduced OVA-induced increases in total and eosinophil counts, and IL-4, IL-5, IL-13, IL-1β, IL-33, and eotaxin levels in bronchoalveolar lavage fluid. Rip2 silencing blocked OVA-induced inflammatory cell infiltration and mucus hypersecretion as observed in lung sections, and mRNA expression of ICAM-1, VCAM-1, E-selectin, RANTES, IL-17, IL-33, thymic stromal lymphopoietin, inducible NO synthase, and MUC5ac in lung tissues. In addition, elevation of serum OVA-specific IgE level in mouse asthma model was markedly suppressed by Rip2 siRNA, together with reduced IL-4, IL-5, and IL-13 production in lymph node cultures. Furthermore, Rip2 siRNA-treated mice produced significantly less airway hyperresponsiveness induced by methacholine. Mechanistically, Rip2 siRNA was found to enhance cytosolic level of IκBα and block p65 nuclear translocation and DNA-binding activity in lung tissues from OVA-challenged mice. Taken together, our findings clearly show that knockdown of Rip2 by gene silencing ameliorates experimental allergic airway inflammation, probably via interruption of NF-κB activity, confirming Rip2 a novel therapeutic target for the treatment of allergic asthma.

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“…(22). In line with this, suppression of Rip2 expression using Rip2 siRNA resulted in abrogation of NF-kB activation (23) and reduction of TSLP and IL-1b expression in mast cells (24,25).…”

Section: Discussionmentioning

confidence: 70%

Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

Goh

Cook

Upton

et al. 2013

The Journal of Immunology

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“…These findings suggest that naringenin protects the TJ barrier through suppression of these signaling pathways induced by DSS and/or inflammatory cytokines in the intestinal epithelial cells. Different studies have indicated that polyphenols, including naringenin, affect intracellular signaling and exhibit physiological effects in cells (2,30).…”

Section: Discussionmentioning

confidence: 99%

Supplemental Naringenin Prevents Intestinal Barrier Defects and Inflammation in Colitic Mice

Azuma

Shigeshiro

Kodama³

et al. 2013

The Journal of Nutrition

129

108

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Intestinal barrier defects are involved in the pathogenesis of inflammatory bowel disease. The present study investigated the ameliorative effects of naringenin, a citrus polyphenol, on intestinal tight junction (TJ) barrier defects and inflammation in a murine model of colitis. In Expt. 1, using a 2 × 2 fractional design, the mice were administered water or 2% dextran sulfate sodium (DSS) in combination with feeding control or naringenin-containing diets for 9 d (severe disease stage). DSS administration caused severe colon damage and inflammation, as indicated by body weight loss, increased clinical sores, colon shortening, and gene expressions of inflammatory cytokines [interferon-γ, interleukin (IL)-6, macrophage inflammatory protein-2, and IL-17A). DSS administration also impaired TJ barrier integrity in the colon, as indicated by increased colon permeability and plasma LPS-binding protein levels, resulting from the impaired colonic expression of TJ proteins, occludin, junctional adhesion molecule-A, and claudin-3. Supplemental feeding with naringenin totally or partially attenuated these symptoms, suggesting that naringenin ameliorates the DSS-induced colitis at least partially through protection of the TJ barrier. In Expt. 2, analyses were performed at different disease stages (d 3, 6, and 9) to more widely examine the ameliorative role of naringenin on the initiation and development of colitis. DSS administration moderately induced colon shortening at d 3 and 6 and increased the disease activity index (DAI) and inflammatory cytokine (IL-6 and IL-17A) expression without any significant increases in colonic permeability. Feeding naringenin attenuated the increased DAI and colon shortening and tended to suppress the increased cytokine expression. These findings suggest that the presence of an additional mechanism underlying the naringenin-mediated, anticolitic effect along with barrier protection.

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“…As discussed later, in spite of only 43% amino acid identity, human and murine TSLP share a significant degree of functional homology (Reche et al, 2001; Sims et al, 2000). During allergic inflammation, the primary producers of TSLP are epithelial cells, keratinocytes and stromal cells, although recent data have demonstrated that both dendritic cells (DCs) and mast cells are capable of TSLP production (Soumelis et al, 2002; Watanabe et al, 2004; Ying et al, 2005; Kashyap, Rochman, Spolski, Samsel, & Leonard, 2011; Moon, Choi, & Kim, 2011). Several groups identified a receptor capable of binding TSLP with low affinity (TSLPR subunit), which shares 24% identity to the common γ receptor chain (γ c ) (Pandey et al, 2000; Park et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

The Biology of Thymic Stromal Lymphopoietin (TSLP)

Ziegler¹,

Roan

Bell

et al. 2013

Advances in Pharmacology

241

207

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Originally shown to promote the growth and activation of B cells, thymic stromal lymphopoietin (TSLP) is now known to have wide-ranging impacts on both hematopoietic and non-hematopoietic cell lineages, including dendritic cells (DCs), basophils, eosinophils, mast cells, CD4+, CD8+ and natural killer (NK) T cells, B cells and epithelial cells. While TSLP's role in the promotion of TH2 responses has been extensively studied in the context of lung- and skin-specific allergic disorders, it is becoming increasingly clear that TSLP may impact multiple disease states within multiple organ systems, including the blockade of TH1/TH17 responses and the promotion of cancer and autoimmunity. This review will highlight recent advances in the understanding of TSLP signal transduction, as well as the role of TSLP in allergy, autoimmunity and cancer. Importantly, these insights into TSLP's multifaceted roles could potentially allow for novel therapeutic manipulations of these disorders.

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Naringenin suppresses the production of thymic stromal lymphopoietin through the blockade of RIP2 and caspase-1 signal cascade in mast cells

Cited by 50 publications

References 26 publications

Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

Supplemental Naringenin Prevents Intestinal Barrier Defects and Inflammation in Colitic Mice

The Biology of Thymic Stromal Lymphopoietin (TSLP)

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