The phosphoinositide 3'-kinase p110d modulates contractile protein production and IL-6 release in human airway smooth muscle

Publisher:
Wiley-Blackwell
Publication Type:
Journal Article
Citation:
Journal of Cellular Physiology, 2012, 227 (8), pp. 3044 - 3052
Issue Date:
2012-01
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Transforming growth factor (TGF) ß1 increases pro-inflammatory cytokines and contractile protein expression by human airway smooth muscle (ASM) cells, which could augment airway inflammation and hyperresponsiveness. Phosphoinositide 3' kinase (PI3K) is one of the signaling pathways implicated in TGFß1 stimulation, and may be altered in asthmatic airways. This study compared the expression of PI3K isoforms by ASM cells from donors with asthma (A), chronic obstructive pulmonary disease (COPD), or neither disease (NA), and investigated the role of PI3K isoforms in the production of TGFß1 induced pro-inflammatory cytokine and contractile proteins in ASM cells. A cells expressed higher basal levels of p110d mRNA compared to NA and COPD cells; however COPD cells produced more p110d protein. TGFß1 increased 110d mRNA expression to the same extent in the three groups. Neither the p110d inhibitor IC87114 (1, 10, 30?µM), the p110ß inhibitor TGX221 (0.1, 1, 10?µM) nor the PI3K pan inhibitor LY294002 (3, 10?µM) had any effect on basal IL-6, calponin or smooth muscle a-actin (a-SMA) expression. However, TGFß1 increased calponin and a-SMA expression was inhibited by IC87114 and LY294002 in all three groups. IC87114, TGX221, and LY294002 reduced TGFß1 induced IL-6 release in a dose related manner in all groups of ASM cells. PI3K p110d is important for TGFß1 induced production of the contractile proteins calponin and a-SMA and the proinflammatory cytokine IL-6 in ASM cells, and may therefore be relevant as a potential therapeutic target to treat both inflammation and airway remodeling.
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