[Interaction between tumor necrosis factor-alpha and the smooth muscle cells of the airway: implication in the physiopathology of asthma].
Asthma is a disease characterized by a bronchial hyperresponsiveness (BHR). Although the underlying mechanisms that induce this increase in bronchial reactivity remain unknown, evidence suggests that the inflammatory process present in the airways could play an important role in the development of BHR. This latter may result from alterations in the intrinsic properties of airway smooth muscle induced by inflammatory mediators. Tumor necrosis factor alpha (TNF alpha), a pro-inflammatory cytokine, appears to be an interesting candidate considering on one hand that it is able to induce, in human and in animals, a BHR to different inhaled pharmacological agents and on the other hand that high levels of TNF alpha were found in asthmatic airways. Our studies show that TNF alpha induces in a direct manner some modifications of the bronchial smooth muscle which can underly an increased muscle contractility. These modifications include an alteration of the intracellular calcium homeostasis and an increase in the mitogen capacity of the human airway smooth muscle cells. Using antibodies directed against the two existing receptor type of TNF alpha (TNFRp55 and TNFRp75) and TNF alpha-analogs obtained by directed mutagenesis, we showed that these modifications result from the activation of TNFRp55. The implication of this receptor in the other pathophysiologic characteristics of asthma is also discussed in this review.
Amrani
Y
Y
INSERM U408, Faculté de Médecine, Paris, France.
Aubier
M
M
Bronner
C
C
D015703:Antigens, CD / Q000502:physiology; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology*; D001980:Bronchi / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001991:Bronchitis / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D008934:Mitogens; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D018836:Inflammation Mediators; D008934:Mitogens; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium