Airway Smooth Muscle

Knox, AJ; Tattersfield, A. E.

doi:10.1007/978-3-642-78920-5_11

Cited by 4 publications

(1 citation statement)

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“…It is possible therefore that the massive PGE 2 production as a result of COX‐2 induction is part of a negative feedback mechanism which is exerting a braking effect on the inflammatory response. As PGI 2 , like PGE 2 , is also coupled to cyclic AMP elevation, it could have a similar protective effect (Knox & Tattersfield, 1994), but this has not been extensively studied. However, PGE 2 at higher concentrations also causes ASM contraction (Sweatman & Collier, 1968; Gardiner, 1975; Armour et al , 1989) due to weak agonism at the thromboxane receptor (Knox & Tattersfield, 1995), and PGF 2α , TXA 2 and PGD 2 are potent pro‐inflammatory modulators which cause bronchoconstriction via the activation of the thromboxane prostanoid receptor (Iwamoto et al , 1995; Johnston et al , 1995; Aizawa et al , 1996).…”

Section: Discussionmentioning

confidence: 99%

Effect of interleukin‐1β, tumour necrosis factor‐α and interferon‐γ on the induction of cyclo‐oxygenase‐2 in cultured human airway smooth muscle cells

Pang

Knox

1997

British J Pharmacology

168

178

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1 Increased levels of several pro-in¯ammatory cytokines including interleukin-1b (IL-1b) and tumour necrosis factor-a (TNFa) have been found in bronchoalveolar lavage¯uid from symptomatic asthmatic patients. are known to stimulate a number of cells to produce in¯ammatory mediators such as prostaglandins. Although airway smooth muscle (ASM) is known to be a rich source of prostaglandins, the regulation of cyclo-oxygenase (COX) isoforms and prostanoid production by proin¯ammatory cytokines have not been studied in human airway smooth muscle. 2 We studied the e ects of IL-1b, TNFa and IFNg on the induction of two isoforms of cyclooxygenase and its relation to prostaglandin E 2 (PGE 2 ) release and COX activity (re¯ected by PGE 2 synthesis from exogenous arachidonic acid) in human cultured airway smooth muscle cells. 3 IL-1b, but not TNFa or IFNg, caused a time-and concentration-dependent enhancement in PGE 2 and other prostanoid (6-keto-PGF 1a , PGF 2a , thromboxane B 2 (TXB 2 ) and PGD 2 ) production, with PGE 2 and 6-keto-PGF 1a as the principal products. This stimulation was accompanied by a corresponding increase in COX activity. 4 COX-2 protein measured by Western blot analysis was not detectable in untreated cells, but was increased in a time-and concentration-dependent manner by IL-1b, but not TNFa or IFNg. In contrast, no variation in the expression of COX-1 protein was observed. 5 Pretreatment with the conventional non-steroidal anti-in¯ammatory drugs (NSAIDs), indomethacin and ibuprofen, and the selective COX-2 inhibitors, NS-398 and nimesulide, completely blocked IL-1b-induced PGE 2 release and COX activity. The glucocorticosteroid dexamethasone and protein synthesis inhibitors, cycloheximide and actinomycin D, not only markedly inhibited IL-1b-stimulated PGE 2 release and COX activity but also suppressed IL-1b-induced COX-2 induction. 6 This study demonstrates that human cultured ASM cells release prostanoids in response to IL-1b stimulation and that the response is mostly mediated by the induction of COX-2 rather than COX-1 isoenzyme, implying that airway smooth muscle may be an important source of prostaglandins in human airways and that COX-2 may play an important role in the regulation of the in¯ammatory process in asthma.

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