M B Sukkar1, J M Hughes, C L Armour, P R Johnson. 1. Respiratory Research Group, Faculty of Pharmacy and Department of Pharmacology, University of Sydney, New South Wales, Australia.
Abstract
OBJECTIVE: Chronic inflammation of the airways is an important component in the induction of airway hyperresponsiveness (AHR) in asthma. The pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) have been implicated in the induction of AHR. Whether these cytokines directly modulate the contractile properties of human airway smooth muscle (ASM) has not been fully investigated. METHODOLOGY: The contractile response to acetylcholine (ACh) (10(-8) to 10(-3) mol/L) was determined in isolated human bronchial segments both prior to and following a 16-h incubation period with IL-1beta (10 or 20 ng/mL) and TNF-alpha (25 ng/mL), either alone or in combination. Incubation of human bronchial segments with IL-1beta/TNF-alpha was also performed in the presence of the COX-1/COX-2 inhibitor, indomethacin. RESULTS: Tumour necrosis factor-alpha potentiated the contractile response to ACh by approximately 27%, while IL-1beta or the cytokines in combination had no effect. Indomethacin had no modulatory effect on the contractile response to ACh in the cytokine-treated tissues. CONCLUSIONS: The relative concentrations of IL-1beta/TNF-alpha in the vicinity of ASM may ultimately determine their effects on ASM contraction in asthma.
OBJECTIVE: Chronic inflammation of the airways is an important component in the induction of airway hyperresponsiveness (AHR) in asthma. The pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) have been implicated in the induction of AHR. Whether these cytokines directly modulate the contractile properties of human airway smooth muscle (ASM) has not been fully investigated. METHODOLOGY: The contractile response to acetylcholine (ACh) (10(-8) to 10(-3) mol/L) was determined in isolated human bronchial segments both prior to and following a 16-h incubation period with IL-1beta (10 or 20 ng/mL) and TNF-alpha (25 ng/mL), either alone or in combination. Incubation of human bronchial segments with IL-1beta/TNF-alpha was also performed in the presence of the COX-1/COX-2 inhibitor, indomethacin. RESULTS:Tumour necrosis factor-alpha potentiated the contractile response to ACh by approximately 27%, while IL-1beta or the cytokines in combination had no effect. Indomethacin had no modulatory effect on the contractile response to ACh in the cytokine-treated tissues. CONCLUSIONS: The relative concentrations of IL-1beta/TNF-alpha in the vicinity of ASM may ultimately determine their effects on ASM contraction in asthma.
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