TNF-α upregulates VCAM-1 and NF-κB in fibroblasts from nasal polyps

Ohori, Junichiro; Ushikai, Masato; Sun, Dong; Nishimoto, Katsutaro; Sagara, Yukari; Fukuiwa, Tatsuya; Matsune, Shoji; Kurono, Yuichi

doi:10.1016/j.anl.2006.05.008

Cited by 21 publications

(25 citation statements)

References 30 publications

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“…The data obtained in the present work are in accordance with this pattern of expression. We also observed that TNF-α significantly increased the nuclear translocation of NFκβ, confirming that this is an important mechanism of induction of pro-inflammatory mediators in NP, as stated by Ohori et al 25 . Thus, our results, as well as previous reports in literature, agree that the main mechanism in which TNF-α induces cytokines production is through activation of TFs.…”

Section: Discussionsupporting

confidence: 91%

In vitro effect of glucocorticoids on nasal polyps

Valera¹,

Brassesco²,

Castro‐Gamero³

et al. 2011

Braz. j. otorhinolaryngol. (Impr.)

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Glucocorticoids are considered the main treatment option for nasal polyps, but their effect is only recently being understood. Aim To evaluate whether fluticasone propionate (FP) inhibits the inflammatory process induced by TNF-alpha in vitro , and to assess if NF-kappaB is associated to this inhibition. Study Design Experimental in vitro study. Materials and Methods Nasal polyp fibroblasts were cultured during 24 hours. Three different concentrations of FP (1, 10 and 100 nM, added to TNF-alpha) were compared to negative (without additive) and positive (TNF-alpha) controls. Gene expression (RTQ-PCR) and protein concentration (ELISA) of VCAM-1, ICAM-1, eotaxin and RANTES were measured, as well as the nuclear translocation of NF-kappaB. Results TNF-alpha significantly increased protein concentration and RNA expression of all the studied molecules, as well as the nuclear translocation of NF-kappaB, when compared to the negative control. FP decreased these parameters in a dose-dependent manner, statistically different from positive control up to 100nM. Conclusions FP extensively inhibited inflammatory recruiters, at both protein and RNA levels, confirming the ability of glucocorticoids to modulate the inflammatory process in nasal polyps. This inhibition was associated to decreased NF-kappaB nuclear translocation, demonstrating that this is an important mechanism of glucocorticoids action for nasal polyps.

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Section: Discussionsupporting

confidence: 91%

In vitro effect of glucocorticoids on nasal polyps

Valera¹,

Brassesco²,

Castro‐Gamero³

et al. 2011

Braz. j. otorhinolaryngol. (Impr.)

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“…Relationship between decreased levels of TNF-a in nasal fluid and shrinkage of polyps can be explained by several recently published findings. Eosinophil infiltration is regulated by numerous chemokines and adhesion molecules such as eotaxin, regulated on activation normal T cell expressed and secreted (RANTES), and vascular cell adhesion molecule (VCAM)-1 (23). To infiltrate sites of inflam mation, eosinophils leave the bloodstream and pass through the endothelium in four steps, namely rolling, adhesion, transendothelial migration, and chemotaxis (23).…”

Section: Discussionmentioning

confidence: 99%

“…Eosinophil infiltration is regulated by numerous chemokines and adhesion molecules such as eotaxin, regulated on activation normal T cell expressed and secreted (RANTES), and vascular cell adhesion molecule (VCAM)-1 (23). To infiltrate sites of inflam mation, eosinophils leave the bloodstream and pass through the endothelium in four steps, namely rolling, adhesion, transendothelial migration, and chemotaxis (23). Adhesion molecules, such as VCAM-1 play an important role during adhesion to endothelial cells (23).…”

Section: Discussionmentioning

confidence: 99%

“…To infiltrate sites of inflam mation, eosinophils leave the bloodstream and pass through the endothelium in four steps, namely rolling, adhesion, transendothelial migration, and chemotaxis (23). Adhesion molecules, such as VCAM-1 play an important role during adhesion to endothelial cells (23). Experiments performed by Ohori et al (23) demonstrated that TNF-a stimulation induces VCAM-1 protein production and mRNA expression in human nasal polyp fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

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Immunomodulatory and Clinical Effects of Long-Term Low-Dose Macrolide Treatment of Chronic Rhinosinusitis with Nasal Polyposis

Perić¹,

Vojvodić²,

Baletić³

et al. 2011

Journal of Medical Biochemistry

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Summary: Immunomodulatory treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) by macrolide antibiotics represents a challenging alternative to conventional therapy and surgery, still being at the very beginning. Immune and inflammatory processes in nasal and paranasal sinus mucosa, crucial in the etiopathogenesis of nasal polyps (NPs) are reflected in levels of various local mediators, found both in mucosa and nasal fluid. In this prospective study, we assessed the immunomodulatory and clinical effects of longterm low-dose oral macrolide treatment in the management of CRSwNP. Twenty-two (n = 22) nonasthmatic, nonallergic patients with CRSwNP were administered clarithromycin (CAM) 500 mg/day single oral dose for eight weeks. We measured the levels of proinflammatory cytokines TNF-a, TNF-b, and IL-1b, Th1 cytokines IL-2, IL-12, and IFN-g, Th2 cytokines IL-4, IL-5, IL-6, and IL-10, and chemokine IL-8 in the nasal fluid samples, before and after treatment, using a flow cytometric method. We also scored each of the 22 patients before and after therapy according to Tsicopoulos' global nasal symptom score and Malm's endoscopic score. Following treatment, we found significantly reduced levels of IL-8 (p<0.01) and TNF-a (p<0.01) in nasal secretions. Macrolide therapy decreased the size of polyps in 45.45% of the patients. We concluded that long-term low-dose treatment with CAM was effective in the management of Kratak sadr`aj: Mada je u samim za~e cima, imunomo dulacijska terapija hroni~nog rinosinuzitisa sa nosnom poli pozom (HRSsNP) primenom makrolidnih anti biotika bi mogla predstavljati alternativu uobi~ajenoj konzer va tivnoj terapiji, kao i hirur{kom le~enju. Imunski i zapaljen ski procesi u sluzoko`i nosa i paranazalnih sinusa, naj zna ~ajniji u etiopato genezi nosnih polipa, reflektuju se na razli~ite lokalne medijatore, detektovane u sluzoko`i kao i u nosnom sekretu. U ovoj prospektivnoj studiji procenili smo imunomo dulacijske i klini~ke efekte dugotrajne niskodozirane oralne primene makrolidnog antibiotika u le~enju HRSsNP. Dva deset dvoje (n = 22) neastmati~nih, nealergi~nih pacijenata sa HRSsNP dobijalo je klaritromicin (CAM) u pojedina~noj dnevnoj dozi od 500 mg tokom osam nedelja. Merene su koncentracije proinflamatornih citokina TNF-a, TNF-b i IL-1b, Th1-cito kina IL-2, IL-12 i IFN-g, Th-2-citokina IL-4, IL-5, IL-6 i IL-10, kao i hemokina IL-8 u uzorcima nosnog sekreta, pre i nakon tera pije, primenom proto~ne citometrije. Svaki od pacijenata klini~ki je klasif i kovan pre i posle le~enja prema Tsicopoulosovom ukupnom nosnom simptom skoru i Malm-ovom endoskopskom skoru. Nakon le~enja, detektovane su znaajno ni`e koncentracije IL-8 (p<0,01) i TNF-a (p<0,01) u nosnom sekretu. Terapija makrolidnim antibio tikom je smanjila veli~inu polipa kod 45,45% od ukupnog bro ja paci jenata. Zaklju~eno je da je dugotrajna nisko dozirana primena

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“…Relationship between decreased levels of TNF-α in nasal fluid and shrinkage of polyps can be explained by several recently published findings. Eosinophil infiltration is regulated by numerous chemokines and adhesion molecules such as eotaxin, regulated on activation of normal T cell expressed and secreted (RANTES), and vascular cell adhesion molecule (VCAM)-1 19 . To infiltrate sites of inflammation, eosinophils leave the bloodstream and pass through the endothelium in four steps, namely rolling, adhesion, transendothelial migration, and chemotaxis 19 .…”

Section: A Peric D Vojvodic N Baletic a Peric O Miljanovicmentioning

confidence: 99%

Influence of Allergy on the Immunomodulatory and Clinical Effects of Long-Term Low-Dose Macrolide Treatment of Nasal Polyposis

Perić¹,

Vojvodić²,

Baletić³

et al. 2010

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aims. Cytokine levels in nasal secretions reflect the inflammatory status of the nasal and paranasal sinus mucosa and the development of mucosal disease. The results of previous investigations suggest that macrolide antibiotics can be effective in treatment of chronic rhinosinusitis and nasal polyposis. The aim of this prospective study was to compare the immunomodulatory and clinical effects of long-term low-dose macrolide treatment of nonatopic and atopic patients with nasal polyposis.Methods. Forty (n = 40) patients with nasal polyposis, 22 allergic and 18 nonallergic were administered clarithromycin (CAM) 500 mg/day single oral dose for eight weeks. We measured the levels of proinflammatory Th1 cytokines TNF-α and IL-1β, Th2 cytokines IL-4, IL-5 and IL-6, and chemokine IL-8 in the nasal fluid samples, before and after treatment, using flow cytometric method. We also scored each of the 40 patients before and after therapy according to nasal symptom score and endoscopic score.Results. Following treatment, we found significantly reduced levels of IL-8 (p<0.01) and TNF-α (p<0.01) in nasal secretions in nonallergic patients. In subjects with nasal polyposis and allergy, we found decreased levels of IL-8 (p<0.01), IL-6 (p<0.05) and IL-1β (p<0.01). Macrolide therapy decreased the size of polyps in 45.45% of nonatopic and in 50% of atopic patients. After macrolide treatment, we found 67.83% patients in nonallergic group and 55.55% patients in allergic group with improved nasal symptoms.Conclusions. Long-term low-dose treatment with CAM was effective in the management of nasal polyposis. Our results showed that macrolide treatment of nasal polyposis have different immunomodulatory and similar clinical effects in allergic and nonallergic patients.

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TNF-α upregulates VCAM-1 and NF-κB in fibroblasts from nasal polyps

Cited by 21 publications

References 30 publications

In vitro effect of glucocorticoids on nasal polyps

In vitro effect of glucocorticoids on nasal polyps

Immunomodulatory and Clinical Effects of Long-Term Low-Dose Macrolide Treatment of Chronic Rhinosinusitis with Nasal Polyposis

Influence of Allergy on the Immunomodulatory and Clinical Effects of Long-Term Low-Dose Macrolide Treatment of Nasal Polyposis

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