Nerve growth factor is released by IL-1beta and induces hyperresponsiveness of the human isolated bronchus.
Nerve growth factor (NGF) is a neurotrophic factor essential for the development and survival of neurons, and is also an important mediator of inflammation. It is released by airway cells stimulated by interleukin (IL)-1beta. As IL-1beta induces airway hyperresponsiveness (AHR) to the tachykinin NK-1 receptor agonist [Sar9,Met(O2)11]-substance P in human isolated bronchi, the aim of this study was to determine whether IL-1beta was able to induce NGF release from isolated bronchi, and whether NGF might participate into IL-1beta-induced AHR. IL-1beta (10 ng x mL(-1); 21 degrees C; 15 h) increased the release of NGF from human isolated bronchi in vitro, and, in organ bath studies, the response of human bronchi to [Sar9,Met(O2)11]-substance P (0.1 microm). A significant correlation was found between these responses. AHR induced by IL-1beta was abolished by a blocking anti-human NGF antibody. Finally, NGF (1 ng x mL(-1); 37 degrees C; 0.5 h) by itself induced a significant increase in [Sar9,Met(O2)11]-substance P responsiveness. By contrast, it did not change the maximal contraction to acetylcholine. In conclusion, the present study clearly demonstrated that nerve growth factor may participate in the airway hyperresponsiveness induced by interleukin-1beta, which supports the neuro-immune cross-talk that may be active in the development of hyperresponsiveness in the human airways, and suggests nerve growth factor is active in the airways in asthma.
EA 3771, Inflammation and environment in asthma, Faculté de pharmacie, Université Louis Pasteur, BP 60024, 67401 Illkirch Cedex, France. nelly.frossard@pharma.u-strasbg.fr
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N
Frossard
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Naline
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Olgart Höglund
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O
Georges
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Advenier
D000704:Analysis of Variance; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D012044:Regression Analysis; D012307:Risk Factors; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques
D007375:Interleukin-1; D009414:Nerve Growth Factors