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.
Frossard
N
N
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
Naline
E
E
Olgart Höglund
C
C
Georges
O
O
Advenier
C
C
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