Effects of Inflammatory Mediators on Pulmonary Airways

Ofir Bachar

    Research output: ThesisDoctoral Thesis (compilation)


    Chronic inflammation is together with excessive contraction of the airways key features of asthma. The aims of the thesis were to analyze the effect of inflammatory mediators on airway smooth muscle, using an in vitro model of cultured murine airways. Additionally, nasal administration of lipopolysaccharides (LPS) to allergic patients was used to evaluate the contribution of LPS to pulmonary inflammation.Nerve growth factor (NGF) enhanced the electric field stimulation (EFS) induced contractions of cultured trachea. Contrary, culture with the related growth factor neurotrophin-3 (NT-3) resulted in reduction of these contractions. Tachykinins induced relaxations of pre-contracted trachea. The relaxation was mediated by the neurokinin-1 receptor via cyclooxygenase (COX)-2 activation and release of prostaglandin (PG) E2. Treatment with tumor necrosis factor ? attenuated the tachykinin-induced relaxations and increased the expression of mRNA for COX-2, PGE2 synthase, PGE2, EP2 receptor and decreased the expression of EP4. Culture in the presence of LPS and poly-I:C, ligands for Toll-like receptor (TLR) 2/4 and TLR3, resulted in an enhancement of bradykinin- and [des-Arg9]-bradykinin-induced contractions and up-regulation of bradykinin B1 and B2 receptors in a NF?B and JNK dependent manner. Nasal LPS provocations of patients with allergic rhinitis increased the recruitment of leukocyte to the nose. However, pre-treatment with pollen prior to LPS resulted in an elevation of both the nasal and the pulmonary levels of nitric oxide in addition to leukocyte recruitment.
    Original languageEnglish
    Awarding Institution
    • Cardell, Lars-Olaf, Supervisor
    Award date2007 Jan 9
    ISBN (Print)978-91-85559-02-2
    Publication statusPublished - 2007

    Bibliographical note

    Defence details

    Date: 2007-01-09
    Time: 13:00
    Place: Lilla Aulan, Entrance 59, Medicinskt Forskningscentrum, UMAS.

    External reviewer(s)

    Name: Dahlén, Sven-Erik
    Title: Prof.
    Affiliation: Experimental Asthma and Allergy Research, Institute of Environmental Medicine, Karolinska Institutet


    <div class="article_info">O Bachar, M Adner, R Uddman and LO Cardell. <span class="article_issue_date">2004</span>. <span class="article_title">Nerve growth factor enhances cholinergic innervation and contractile response to electric field stimulation in a murine in vitro model of chronic asthma.</span> <span class="journal_series_title">Clin Exp Allergy</span>, <span class="journal_volume">vol 34</span> <span class="journal_pages">pp 1137-45</span>.</div>
    <div class="article_info">O Bachar, M Adner, R Uddman and LO Cardell. <span class="article_issue_date">2005</span>. <span class="article_title">Prolonged exposure to NT-3 attenuates cholinergic nerve-mediated contractions in cultured murine airways.</span> <span class="journal_series_title">Respir Physiol Neurobiol</span>, <span class="journal_volume">vol 147</span> <span class="journal_pages">pp 81-9</span>.</div>
    <div class="article_info">O Bachar, AC Rose, M Adner, X Wang, CE Prendergast, A Kempf, NP Shankley and LO Cardell. <span class="article_issue_date">2005</span>. <span class="article_title">TNFalpha reduces tachykinin, PGE2-dependent, relaxation of the cultured mouse trachea by increasing the activity of COX-2.</span> <span class="journal_series_title">Br J Pharmacol</span>, <span class="journal_volume">vol 144</span> <span class="journal_pages">pp 220-30</span>.</div>
    <div class="article_info">O Bachar, M Adner, R Uddman and LO Cardell. <span class="article_issue_date">2004</span>. <span class="article_title">Toll-like receptor stimulation induces airway hyper-responsiveness to bradykinin, an effect mediated by JNK and NF-KB signaling pathways.</span> <span class="journal_series_title">Eur J Immunol</span>, <span class="journal_volume">vol 34</span> <span class="journal_pages">pp 1196-207</span>.</div>
    <div class="article_info">O Bachar, J Gustafsson, L Jansson, M Adner and LO Cardell. <span class="article_issue_date"></span>. <span class="article_title">LPS administration to the allergic nose contributes to lower airway inflammation.</span> <span class="journal_series_title">Clin Exp Allergy</span>, (submitted)</div>

    Subject classification (UKÄ)

    • Respiratory Medicine and Allergy

    Free keywords

    • electric ?eld stimulation
    • bradykinin
    • airway
    • tumor necrosis factor a
    • Respiratory system
    • nitric oxide
    • Andningsorganen
    • Toll-like receptor
    • prostaglandin E2
    • neurotrophin
    • allergy


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