Elastolytic activity and alveolar epithelial type-1 cell damage after chronic LPS inhalation: Effects of dexamethasone and rolipram

Johnson, Frederick J.; Reynolds, Lucy; Toward, Toby J.

doi:10.1016/j.taap.2005.01.006

Cited by 13 publications

(7 citation statements)

References 41 publications

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“…ELA activity was assessed by a modified method previously described (22). Briefly, supernatant samples from each individual were incubated with insoluble elastin‐Congo Red dye (E0502‐5G † ) diluted in 100 m m Tris–HCl buffer (pH 8·8) containing 0·01% sodium azide † in a 96‐well plate.…”

Section: Methodsmentioning

confidence: 99%

Differences between salivary and blood neutrophils from elderly and young denture wearers

Gasparoto¹,

Vieira²,

Porto³

et al. 2010

Journal of Oral Rehabilitation

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We previously showed that neutrophils from patients with Candida-related denture stomatitis exhibited damaged function, and the advance in age intensified this condition. Because such alterations had been determined in elderly people that were not denture wearers, the purpose of this study was to clarify functional and phenotypic characteristics of neutrophils from elderly denture wearers (EDW) and young denture wearers (YDW) without oral lesion. We enrolled 20 denture wearers (12 EDW and 8 YDW) and determined the positivity of Candida species on maxillary prosthesis and palate. Additionally, blood and salivary neutrophils were evaluated. Furthermore, cytokines and chemokines salivary levels were detected. YDW presented higher positivity of Candida albicans than elderly ones. However, blood neutrophils from EDW expressed less CXCR1, CD62L and CD11b and had lower C. albicans phagocytosis than YDW. Although myeloperoxidase and elastase activity was significantly higher in C. albicans-stimulated blood neutrophils from elderly, they produced high levels of IL-10 and low levels of Granulocyte macrophage-colony stimulating factor (GM-CSF). Despite apoptosis rate of salivary neutrophils was enhanced, these cells were at a high number in YDW. GM-CSF and IL10 were lower in saliva from elderly group. These data confirmed that ageing affects blood and salivary neutrophils and could predispose elderly to persistent oral infections.

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Section: Methodsmentioning

confidence: 99%

Differences between salivary and blood neutrophils from elderly and young denture wearers

Gasparoto¹,

Vieira²,

Porto³

et al. 2010

Journal of Oral Rehabilitation

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“…Further, comparison with equivalent (and maximal) concentrations of RO0251553 demonstrated comparable efficacy. Limited studies were performed to compare the duration of action of RO5024118 and RO0251553 in this guinea pig in vivo model because the levels of neutrophil elastase in naïve animals is low and therefore the applicability of such an animal model to the clinical situation in COPD lungs must be interpreted with caution (Johnson et al ., 2005). RO5024118 retained bronchodilatory activity for 2 h, whereas RO0251553 did not.…”

Section: Discussionmentioning

confidence: 99%

Dual bronchodilatory and pulmonary anti‐inflammatory activity of RO5024118, a novel agonist at vasoactive intestinal peptide VPAC₂ receptors

Tannu

Renzetti

Tare

et al. 2010

British J Pharmacology

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Vasoactive intestinal peptide is expressed in the respiratory tract and induces its effects via its receptors, VPAC1 and VPAC2. RO5024118 is a selective VPAC2 receptor agonist derived via chemical modification of an earlier VPAC2 agonist, RO0251553. In the present studies, we characterized the pharmacological activity of RO5024118. EXPERIMENTAL APPROACHStability of RO5024118 to human neutrophil elastase was assessed. Bronchodilatory activity of RO5024118 was investigated in guinea pig and human isolated airway smooth muscle preparations and in a guinea pig bronchoconstriction model. Pulmonary anti-inflammatory activity of RO5024118 was investigated in a lipopolysaccharide mouse model and in a porcine pancreatic elastase (PPE) rat model. KEY RESULTSRO5024118 demonstrated increased stability to neutrophil elastase compared with RO0251553. In human and guinea pig isolated airway preparations, RO5024118 induced bronchodilatory effects comparable with RO0251553 and the long-acting b-agonist salmeterol and was significantly more potent than native vasoactive intestinal peptide and the short-acting b-agonist salbutamol. In 5-HT-induced bronchoconstriction in guinea pigs, RO5024118 exhibited inhibitory activity with similar efficacy as, and longer duration than, RO0251553. In a lipopolysaccharide-mouse model, RO5024118 inhibited neutrophil and CD8 + cells and myeloperoxidase levels. In rats, intratracheal instillation of PPE induced airway neutrophilia that was resistant to dexamethasone. Pretreatment with RO5024118 significantly inhibited PPE-induced neutrophil accumulation. CONCLUSIONS AND IMPLICATIONSThese results demonstrate that RO5024118 induces dual bronchodilatory and pulmonary anti-inflammatory activity and may be beneficial in treating airway obstructive and inflammatory diseases.

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“…Salivary ELA activity was assessed by a modified method previously described 16 . Briefly, samples from each individual were incubated with insoluble elastin‐Congo Red dye (E0502‐5G; Sigma‐Aldrich) diluted in 100 mM Tris–HCl buffer (pH 8.8) containing 0.01% sodium azide (Sigma‐Aldrich) in a 96‐well plate.…”

Section: Methodsmentioning

confidence: 99%

Salivary immunity in elderly individuals presented with Candida‐related denture stomatitis

et al. 2011

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Salivary immunity in elderly individuals presented with Candida-related denture stomatitisObjectives: Elderly individuals with Candida-related denture stomatitis (DS) present with a reduced defence against Candida albicans. This study evaluated levels of antimicrobial mediators in the elderly DS saliva and salivary neutrophils' activation characteristics compared with elderly and young without DS. Methods: Salivary peroxidases (SPO) and elastase activities (ELA), nitric oxide (NO), transforming growth factor beta (TGF-b), IL-6 and CCL3 production were determined in saliva from elderly with or without DS, and young control individuals. TLR4, CXCR1, CD11b, CD16 and CD32 expression on salivary neutrophils were evaluated. Correlations between number and apoptosis rate of salivary neutrophils, enzymatic activities and cytokine levels were determined. Results: Elderly DS individuals exhibited the lowest SPO and ELA activities. Also, the activity of both enzymes was low in elderly without DS. Although both elderly groups showed higher salivary NO and TGF-b levels compared to young control groups, elderly DS presented the highest salivary NO, TGF-b, IL-6 and CCL3 levels. Decreased percentages of salivary TLR4 + and CD16 + neutrophils were detected in both elderly groups. Although these damages could influence the establishment and persistence of DS, the highest levels of salivary IL-6 and CCL3 in elderly DS could be preventing more serious complications.

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Elastolytic activity and alveolar epithelial type-1 cell damage after chronic LPS inhalation: Effects of dexamethasone and rolipram

Cited by 13 publications

References 41 publications

Differences between salivary and blood neutrophils from elderly and young denture wearers

Differences between salivary and blood neutrophils from elderly and young denture wearers

Dual bronchodilatory and pulmonary anti‐inflammatory activity of RO5024118, a novel agonist at vasoactive intestinal peptide VPAC₂ receptors

Salivary immunity in elderly individuals presented with Candida‐related denture stomatitis

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Elastolytic activity and alveolar epithelial type-1 cell damage after chronic LPS inhalation: Effects of dexamethasone and rolipram

Cited by 13 publications

References 41 publications

Differences between salivary and blood neutrophils from elderly and young denture wearers

Differences between salivary and blood neutrophils from elderly and young denture wearers

Dual bronchodilatory and pulmonary anti‐inflammatory activity of RO5024118, a novel agonist at vasoactive intestinal peptide VPAC2 receptors

Salivary immunity in elderly individuals presented with Candida‐related denture stomatitis

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Dual bronchodilatory and pulmonary anti‐inflammatory activity of RO5024118, a novel agonist at vasoactive intestinal peptide VPAC₂ receptors