Expressions of nuclear factor-kappa B p50 and p65 and their significance in the up-regulation of intercellular cell adhesion molecule-1 mRNA in the nasal mucosa of allergic rhinitis patients

Wang, Shi Zhen; Mei, Feng Jun; Zhao, Jianxing

doi:10.1007/s00405-012-2136-y

Cited by 13 publications

(15 citation statements)

References 11 publications

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“…Although a previous study reported that the expression levels of ICAM-1 did not increase in the positive control group or decrease in the TNF-α treatment group,26 ICAM-1 has been reported to play an important role in local inflammation and eosinophil infiltration, and gene expression is regulated by NF-κB 27. Wang et al7 showed that the expression of NF-κB p50 and p65 has a significant positive correlation with that of ICAM-1 mRNA, and NF-κB plays an important role in ICAM-1 transcription in the nasal mucosa of AR patients. The decrease in the expression of ICAM-1 protein suggests that local inhibition of NF-κB leads to a decrease in the transcription of ICAM-1 and prevents adhesion of eosinophils on endothelial cells, thus inhibiting eosinophil infiltration in the nasal mucosa.…”

Section: Discussionmentioning

confidence: 95%

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Inhibition of Allergic Response by Intranasal Selective NF-κB Decoy Oligodeoxynucleotides in a Murine Model of Allergic Rhinitis

Wee

Zhang

Rhee

et al. 2017

Allergy Asthma Immunol Res

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PurposeIt remains unknown whether local inhibition of Nuclear factor-kappa B (NF-κB) could have therapeutic value in the treatment of allergic rhinitis (AR). This study aimed to evaluate the effect of selective NF-κB inhibition using NF-κB decoy oligodeoxynucleotides (ODNs) for the local treatment of AR in ovalbumin (OVA)-sensitized wild-type mice.MethodsBALB/c mice were sensitized with OVA and alum, and then challenged intranasally with OVA. NF-κB decoy ODNs were given intranasally to the treatment group, and NF-κB scrambled ODNs were given to the sham treatment group. Allergic symptom scores, eosinophil infiltration, cytokine levels in the nasal mucosa, nasal lavage fluid, and spleen cell culture, serum total and OVA-specific immunoglobulins, as well as intercellular adhesion molecure-1 (ICAM-1) in the nasal mucosa, were analyzed.ResultsNF-κB decoy ODNs significantly reduced allergic symptoms and eosinophil infiltration in the nasal mucosa. They also suppressed serum levels of total IgE, OVA-specific IgE, and IgG1. IL-5 and TNF-α levels and the expression of ICAM-1 were decreased in the nasal mucosa of the treatment group compared to the positive control and sham treatment groups. In addition, IL-6 levels were significantly decreased in the nasal lavage fluid of the treatment group. Furthermore, NF-κB decoy ODNs significantly reduced expression of the systemic Th2 cytokines, IL-4 and IL-5 in spleen cell culture.ConclusionsThis study demonstrates for the first time that local NF-κB inhibition using NF-κB decoy ODNs suppressed the allergic response in a murine AR model. This shows the therapeutic potential of local NF-κB inhibition in the control of AR.

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Section: Discussionmentioning

confidence: 95%

“…However, information regarding the association of local NF-κB inhibition with allergic inflammation in AR is limited, although it has been demonstrated in humans and animal models that NF-κB is up-regulated in the nasal mucosa of patients with allergic rhinitis (AR) 789…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Allergic Response by Intranasal Selective NF-κB Decoy Oligodeoxynucleotides in a Murine Model of Allergic Rhinitis

Wee

Zhang

Rhee

et al. 2017

Allergy Asthma Immunol Res

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“…As an important regulator of proinflammatory gene expression, synthesis of cytokines such as IL-1 β , IL-6, IL-8, and TNF- α is mediated by NF- κ B. Activation of NF- κ B may induce human inflammatory diseases [150, 151]. It was reported that negatively charged poly(acrylic acid-) conjugated GNP activated the NF- κ B signalling pathway in THP-1 cells.…”

Section: The Mechanisms Of Immunomodulation Induced By Npsmentioning

confidence: 99%

Immunomodulation of Nanoparticles in Nanomedicine Applications

Jiao

Liu

et al. 2014

BioMed Research International

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Nanoparticles (NPs) have promising applications in medicine. Immune system is an important protective system to defend organisms from non-self matters. NPs interact with the immune system and modulate its function, leading to immunosuppression or immunostimulation. These modulating effects may bring benefits or danger. Compositions, sizes, and surface chemistry, and so forth, affect these immunomodulations. Here we give an overview of the relationship between the physicochemical properties of NPs, which are candidates to be applied in medicine, and their immunomodulation properties.

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“…We employed serial nasosorption sampling and measured levels of soluble chemokines and cytokines using a multiplex immunoassay system. In addition, nasal epithelial curettage samples were taken for analysis of mRNA (transcriptomics) for intercellular cell adhesion molecule-1 (ICAM-1) that is elevated in the nasal mucosa in allergic rhinitis [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness

et al. 2015

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Background Practical methods of monitoring innate immune mucosal responsiveness are lacking. Lipopolysaccharide (LPS) is a component of the cell wall of Gram negative bacteria and a potent activator of Toll-like receptor (TLR)-4. To measure LPS responsiveness of the nasal mucosa, we administered LPS as a nasal spray and quantified chemokine and cytokine levels in mucosal lining fluid (MLF).MethodsWe performed a 5-way cross-over, single blind, placebo-controlled study in 15 healthy non-atopic subjects (n = 14 per protocol). Doses of ultrapure LPS (1, 10, 30 or 100μg/100μl) or placebo were administered by a single nasal spray to each nostril. Using the recently developed method of nasosorption with synthetic adsorptive matrices (SAM), a series of samples were taken. A panel of seven cytokines/chemokines were measured by multiplex immunoassay in MLF. mRNA for intercellular cell adhesion molecule-1 (ICAM-1) was quantified from nasal epithelial curettage samples taken before and after challenge.ResultsTopical nasal LPS was well tolerated, causing no symptoms and no visible changes to the nasal mucosa. LPS induced dose-related increases in MLF levels of IL-1β, IL-6, CXCL8 (IL-8) and CCL3 (MIP-1α) (AUC at 0.5 to 10h, compared to placebo, p<0.05 at 30 and 100μg LPS). At 100μg LPS, IL-10, IFN-α and TNF-α were also increased (p<0.05). Dose-related changes in mucosal ICAM-1 mRNA were also seen after challenge, and neutrophils appeared to peak in MLF at 8h. However, 2 subjects with high baseline cytokine levels showed prominent cytokine and chemokine responses to relatively low LPS doses (10μg and 30μg LPS).ConclusionsTopical nasal LPS causes dose-dependent increases in cytokines, chemokines, mRNA and cells. However, responsiveness can show unpredictable variations, possibly because baseline innate tone is affected by environmental factors. We believe that this new technique will have wide application in the study of the innate immune responses of the respiratory mucosa.Key MessagesUltrapure LPS was used as innate immune stimulus in a human nasal challenge model, with serial sampling of nasal mucosal lining fluid (MLF) by nasosorption using a synthetic absorptive matrix (SAM), and nasal curettage of mucosal cells. A dose response could be demonstrated in terms of levels of IL-1β, IL-6, CXCL8 and CCL3 in MLF, as well as ICAM-1 mRNA in nasal curettage specimens, and levels of neutrophils in nasal lavage. Depending on higher baseline levels of inflammation, there were occasional magnified innate inflammatory responses to LPS.Trial RegistrationClinical Trials.gov NCT02284074

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Expressions of nuclear factor-kappa B p50 and p65 and their significance in the up-regulation of intercellular cell adhesion molecule-1 mRNA in the nasal mucosa of allergic rhinitis patients

Cited by 13 publications

References 11 publications

Inhibition of Allergic Response by Intranasal Selective NF-κB Decoy Oligodeoxynucleotides in a Murine Model of Allergic Rhinitis

Inhibition of Allergic Response by Intranasal Selective NF-κB Decoy Oligodeoxynucleotides in a Murine Model of Allergic Rhinitis

Immunomodulation of Nanoparticles in Nanomedicine Applications

Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness

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