Effects of Inflammatory Mediators on Pulmonary Airways

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

Toll-Like Receptor activation in Airway Smooth Muscle- Dual actions, via Separate MAPK Pathways.

paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination. Citation for the published paper

Lipopolysaccharide administration to the allergic nose contributes to lower airway inflammation.

Abstract is not availabl

Leukocyte phenotype changes induced by specific immunotherapy in patients with birch allergy.

The underlying mechanisms of allergen-specific immunotherapy (SIT) are not fully understood