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Effects of Inflammatory Mediators on Pulmonary Airways

Bachar, Ofir LU (2007)
Abstract
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... (More)
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. (Less)
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author
supervisor
opponent
  • Prof. DahlĂ©n, Sven-Erik, Experimental Asthma and Allergy Research, Institute of Environmental Medicine, Karolinska Institutet
organization
publishing date
type
Thesis
publication status
published
subject
keywords
electric ?eld stimulation, bradykinin, airway, tumor necrosis factor a, Respiratory system, nitric oxide, Andningsorganen, Toll-like receptor, prostaglandin E2, neurotrophin, allergy
pages
127 pages
publisher
Medicinska fakulteten, Lunds universitet
defense location
Lilla Aulan, Entrance 59, Medicinskt Forskningscentrum, UMAS.
defense date
2007-01-09 13:00:00
ISBN
978-91-85559-02-2
language
English
LU publication?
yes
additional info
O Bachar, M Adner, R Uddman and LO Cardell. 2004. Nerve growth factor enhances cholinergic innervation and contractile response to electric field stimulation in a murine in vitro model of chronic asthma. Clin Exp Allergy, vol 34 pp 1137-45.
O Bachar, M Adner, R Uddman and LO Cardell. 2005. Prolonged exposure to NT-3 attenuates cholinergic nerve-mediated contractions in cultured murine airways. Respir Physiol Neurobiol, vol 147 pp 81-9.
O Bachar, AC Rose, M Adner, X Wang, CE Prendergast, A Kempf, NP Shankley and LO Cardell. 2005. TNFalpha reduces tachykinin, PGE2-dependent, relaxation of the cultured mouse trachea by increasing the activity of COX-2. Br J Pharmacol, vol 144 pp 220-30.
O Bachar, M Adner, R Uddman and LO Cardell. 2004. Toll-like receptor stimulation induces airway hyper-responsiveness to bradykinin, an effect mediated by JNK and NF-KB signaling pathways. Eur J Immunol, vol 34 pp 1196-207.
O Bachar, J Gustafsson, L Jansson, M Adner and LO Cardell. . LPS administration to the allergic nose contributes to lower airway inflammation. Clin Exp Allergy, (submitted)
id
c8120ff3-92db-4958-8927-40bb10d9f762 (old id 547962)
date added to LUP
2016-04-04 09:59:40
date last changed
2018-11-21 20:56:06
@phdthesis{c8120ff3-92db-4958-8927-40bb10d9f762,
  abstract     = {{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.}},
  author       = {{Bachar, Ofir}},
  isbn         = {{978-91-85559-02-2}},
  keywords     = {{electric ?eld stimulation; bradykinin; airway; tumor necrosis factor a; Respiratory system; nitric oxide; Andningsorganen; Toll-like receptor; prostaglandin E2; neurotrophin; allergy}},
  language     = {{eng}},
  publisher    = {{Medicinska fakulteten, Lunds universitet}},
  school       = {{Lund University}},
  title        = {{Effects of Inflammatory Mediators on Pulmonary Airways}},
  year         = {{2007}},
}