Role and mechanism of thromboxane-induced proliferation of cultured airway smooth muscle cells
| Autor: | Michael M. Grunstein, J. P. Noveral |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Leukotriene D4 Physiology Respiratory System Inositol 1 4 5-Trisphosphate Phospholipases A Thromboxane A2 chemistry.chemical_compound Phospholipase A2 Physiology (medical) Internal medicine medicine Animals Autocrine signalling Cells Cultured Leukotriene biology Phospholipase C Dose-Response Relationship Drug Cell growth Muscle Smooth Cell Biology respiratory system respiratory tract diseases Cell biology Phospholipases A2 Endocrinology Mechanism of action chemistry Type C Phospholipases biology.protein lipids (amino acids peptides and proteins) Rabbits medicine.symptom Cell Division circulatory and respiratory physiology Signal Transduction |
| Zdroj: | The American journal of physiology. 263(5 Pt 1) |
| ISSN: | 0002-9513 |
| Popis: | Thromboxane (Tx)A2 has been reported to play an important role in modulating airway contractility under various conditions associated with airways inflammation. To identify its potential role in contributing to airway smooth muscle (ASM) hyperplasia, a characteristic feature of asthmatic airways, the mitogenic effect and mechanism of action of TxA2 were investigated in cultured rabbit ASM cells. The stable TxA2 mimetics, carbocyclic TxA2 (CTA2) and U-46619, elicited dose-dependent (10(-12) to 10(-6) M) increases in ASM cell number and induced acute augmentation of intracellular inositol 1,4,5-trisphosphate accumulation. The latter action was blocked by neomycin, a phospholipase C inhibitor; however, neomycin had no effect on the promitogenic action of the TxA2 mimetics. In contrast, TxA2-induced ASM cell proliferation was inhibited by inhibitors of phospholipase A2 and 5-lipoxygenase, as well as blockade of the leukotriene (LT)D4 receptor. Moreover, in complementary studies, we found that exogenous administration of LTD4 (10(-14) to 10(-6) M) potently induced ASM cell proliferation and that the TxA2 mimetics evoked the enhanced release of endogenous leukotrienes from the cultured ASM cells. Taken together, these observations provide new evidence that 1) TxA2 stimulates ASM cell proliferation; 2) the promitogenic effect of TxA2 is associated with activation of phospholipase A2; and 3) the latter mediates ASM cell proliferation via the release and autocrine mitogenic action of leukotrienes. The findings support a potential role for TxA2 in contributing to the characteristic increase in ASM cell mass obtained in asthma and other chronic airway diseases. |
| Databáze: | OpenAIRE |
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