Differential Expression of Estrogen Receptor Variants in Response to Inflammation Signals in Human Airway Smooth Muscle

Prostanoids may be involved in bradykinin (BK)-induced bronchoconstriction in asthma. We investigated whether cyclooxygenase (COX)-2 induction was involved in prostaglandin (PG) E2 release by BK in cultured human airway smooth muscle (ASM) cells and analyzed the BK receptor subtypes responsible. BK stimulated PGE2release, COX activity, and COX-2 induction in a concentration- and time-dependent manner. It also time dependently enhanced arachidonic acid release. In short-term (15-min) experiments, BK stimulated PGE2 generation but did not increase COX activity or induce COX-2. In long-term (4-h) experiments, BK enhanced PGE2 release and COX activity and induced COX-2. The long-term responses were inhibited by the protein synthesis inhibitors cycloheximide and actinomycin D and the steroid dexamethasone. The effects of BK were mimicked by the B2-receptor agonist [Tyr(Me)8]BK, whereas the B1 agonist des-Arg9-BK was weakly effective at high concentrations. The B2antagonist HOE-140 potently inhibited all the effects, but the B1 antagonist des-Arg9,(Leu8)-BK was inactive. This study is the first to demonstrate that BK can induce COX-2. Conversion of increased arachidonic acid release to PGE2 by COX-1 is mainly involved in the short-term effect, whereas B2 receptor-related COX-2 induction is important in the long-term PGE2 release.

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A human airway smooth muscle cell line that retains physiological responsiveness

AJP Cell Physiology ◽

10.1152/ajpcell.1989.256.2.c329 ◽

1989 ◽

Vol 256 (2) ◽

pp. C329-C335 ◽

Cited By ~ 245

Author(s):

R. A. Panettieri ◽

R. K. Murray ◽

L. R. DePalo ◽

P. A. Yadvish ◽

M. I. Kotlikoff

Keyword(s):

Smooth Muscle ◽

Cell Line ◽

Airway Smooth Muscle ◽

Cytosolic Calcium ◽

Airway Smooth Muscle Cell ◽

Airway Smooth Muscle Cells ◽

Functional Coupling ◽

Functional Responses ◽

Human Airway Smooth Muscle ◽

Human Airway

We report the development of a nontransformed line of human airway smooth muscle cells retaining smooth muscle-specific contractile protein expression and physiological responsiveness to agonists implicated in inflammatory airway diseases. Specific responses to histamine, leukotrienes, bradykinin, platelet-activating factor, substance P, and thromboxane analogues are demonstrated as well as functional coupling to beta-adrenergic receptors. The cell line was characterized using indirect immunofluorescence, as well as electrophoretic separation and immunoblot analysis of smooth muscle-specific actin. Functional responses were assessed by measurements of cytosolic calcium and stimulation of adenosine 3',5'-cyclic monophosphate production. The cells retain their responsiveness over many population doublings and should be a useful model to examine specific receptor-effector mechanisms, as well as the effects of neurohumoral agents on the regulation of airway smooth muscle growth and differentiation.

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