Asthma Mediators: Current Views

Spina, Domenico

doi:10.1211/0022357001773779

Cited by 9 publications

(4 citation statements)

References 265 publications

(271 reference statements)

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“…The biology and function of the various cell types and mediators involved in asthma have been explored in many studies 5–7 . Regardless of the triggering stimulus, contraction of the ASM has been considered to be the final pathway leading to the manifestation of various symptoms associated with asthma.…”

Section: Airway Hyperresponsiveness and Airway Inflammation In Asthmamentioning

confidence: 99%

Transient receptor potential and other ion channels as pharmaceutical targets in airway smooth muscle cells

Ong¹,

Barritt²

2004

Respirology

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Regardless of the triggering stimulus in asthma, contraction of the airway smooth muscle (ASM) is considered to be an important pathway leading to the manifestation of asthmatic symptoms. Therefore, the various ion channels that modulate ASM contraction and relaxation are particularly attractive targets for therapy. Although voltage-operated Ca2+ channels (VOCC) are the most extensively characterised Ca(2+)-permeable channels in ASM cells and are obvious pharmacological targets, blockers of VOCC have not been successful in alleviating ASM contraction in asthma. Similarly, although the Cl- and K+ channels also modulate ASM contraction and relaxation by regulating plasma membrane potential, pharmacological interventions directed against these channels have failed to abrogate ASM contraction in asthma. A large body of evidence suggests that store-operated Ca2+ channels (SOCC) and Ca(2+)-permeable second messenger-activated non-selective cation channels (NSCC) predominantly mediate ASM contraction. However, development of pharmacological interventions involving these channels has been hampered by the paucity of information regarding their molecular identity. Members of the mammalian transient receptor potential (TRP) protein family, which form voltage-independent channels with variable Ca2+ selectivity that are activated by store depletion and/or by intracellular messengers, are potential molecular candidates for SOCC and NSCC in ASM cells. While the function of TRP channels in ASM cells remains to be elucidated and there are, at present, essentially no good TRP channel antagonists, this group of proteins is a potentially valuable pharmaceutical target for the treatment of asthma.

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Section: Airway Hyperresponsiveness and Airway Inflammation In Asthmamentioning

confidence: 99%

Transient receptor potential and other ion channels as pharmaceutical targets in airway smooth muscle cells

Ong¹,

Barritt²

2004

Respirology

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“…The upsurge of inflammatory mediators, including serum IgE, serves as evidence of the onset of asthma ( 20 , 21 ). Therefore, OVA-specific IgE levels were measured in the serum of OVA-sensitized mice treated with vehicle, Dex, AePG or SEAC to evaluate the suppressive effects on IgE production.…”

Section: Resultsmentioning

confidence: 99%

Saponin-enriched extract of Asparagus cochinchinensis alleviates airway inflammation and remodeling in ovalbumin-induced asthma model

Sung

Lee

Kim

et al. 2017

International Journal of Molecular Medicine

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Asthma is a chronic inflammatory disease characterized by T-lymphocyte and eosinophil infiltration, mucus overproduction and airway hyper-responsiveness. The present study examined the therapeutic effects and action mechanism of a saponin-enriched extract of Asparagus cochinchinensis (SEAC) on airway inflammation and remodeling in an ovalbumin (OVA)-induced asthma model. To accomplish this, alterations of the nitric oxide (NO) level, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels, as well as variations in immune cell numbers, immunoglobulin E (IgE) concentration, histopathological structure and inflammatory cytokine levels were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells or an OVA-induced mouse model of asthma treated with SEAC. The concentration of NO and mRNA levels of COX-2 and iNOS were significantly decreased in the SEAC + LPS-treated RAW264.7 cells compared with the vehicle + LPS-treated RAW264.7 cells. Additionally, in the OVA-induced asthma model, the number of immune cells in the bronchoalveolar lavage fluid, the concentration of OVA-specific IgE, the infiltration of inflammatory cells, the bronchial thickness and the levels of the inflammatory mediators interleukin-4 (IL-4), IL-13 and COX-2 were significantly lower in the OVA + SEAC-treated group compared with the OVA + vehicle-treated group. In addition, a significant reduction in goblet cell hyperplasia, peribronchiolar collagen layer thickness and VEGF expression for airway remodeling was detected in the OVA + SEAC-treated group compared with the OVA + vehicle-treated group. These findings indicate that SEAC is a suppressor of airway inflammation and remodeling, and may therefore be useful as an anti-inflammatory drug for the treatment of asthma.

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“…The mechanism by which indomethacin induces an increase in airway responsiveness to histamine is still uncertain. It has been attributed to a vagal stimulation, as the effect is abolished in vagotomized animals ( Ito & Tajima, 1981 ), but also to the inhibition of airway derived PGE 2 , which is known to have a bronchoprotective effect ( Pavord & Tattersfield, 1995 ; Spina, 2000 ). A further possibility is that NSAIDs attenuate adrenergic and non‐adrenergic inhibitory activity thereby leading to an increase in airway responsiveness ( McCullock et al ., 1967 ; Coburn & Tomita, 1973 ).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of a PAR2‐activating peptide on histamine‐induced bronchoconstriction in guinea‐pig

Cicala

Spina

Keir

et al. 2001

British J Pharmacology

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1 Protease activated receptor-2 (PAR2) is a seven transmembrane domain G protein coupled receptor proteolytically activated. PAR2, together with other PARs, can be also activated by peptides mimicking the sequence of the receptor tethered ligand. We have evaluated the eect of systemic administration of a peptide activating PAR2 (PAR2-AP, SLIGRL) on histamine-induced increase in lung resistances in the guinea-pig. 2 Intravenous administration of PAR2-AP (1 mg kg 71 ) signi®cantly inhibited histamine-induced increase in lung resistance in a time-dependent fashion that was not abolished by indomethacin or vagotomy.3 Bronchoprotective eect of PAR2-AP was not reversed by the cyclo-oxygenase inhibitor, indomethacin, the nitric oxide synthetase inhibitor, L-NAME, nor by the non-selective betaantagonist, propranolol. 4 Indomethacin augmented the bronchoconstriction to histamine which was inhibited by PAR2-AP. Furthermore, in vagotomized animals, the bronchial hyper-responsiveness to histamine was signi®cantly reduced, and in these circumstances, PAR2-AP still retained the capacity to provide bronchoprotection against histamine. 5 PAR2-AP also produced a modest reduction in histamine-induced protein leakage in trachea and upper bronchi. 6 Our results indicated that PAR2 might have a bronchoprotective role in the guinea-pig in vivo independent of prostaglandin or nitric oxide release.

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Asthma Mediators: Current Views

Cited by 9 publications

References 265 publications

Transient receptor potential and other ion channels as pharmaceutical targets in airway smooth muscle cells

Transient receptor potential and other ion channels as pharmaceutical targets in airway smooth muscle cells

Saponin-enriched extract of Asparagus cochinchinensis alleviates airway inflammation and remodeling in ovalbumin-induced asthma model

Protective effect of a PAR2‐activating peptide on histamine‐induced bronchoconstriction in guinea‐pig

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