Impaired cAMP production in human airway smooth muscle cells by bradykinin: role of cyclooxygenase products

Interleukin (IL)-1β impairs human airway smooth muscle (ASM) cell cAMP responses to isoproterenol (Iso). We investigated if bradykinin (BK) could cause a similar effect and the role of cyclooxygenase (COX) products in this event, since we have recently reported that BK, like IL-1β, also causes COX-2 induction and prostanoid release in human ASM cells. BK pretreatment significantly attenuated Iso-induced cAMP generation in a time- and concentration-dependent manner. cAMP generation by prostaglandin (PG) E2but not by forskolin was also impaired. The COX inhibitor indomethacin completely prevented the impairment, whereas the selective COX-2 inhibitors NS-398 and nimesulide, protein synthesis inhibitors cycloheximide and actinomycin D, and steroid dexamethasone were all partially effective. The impairment was mimicked by the B2agonist [Tyr(Me)8]BK, the Ca2+ionophore A-23187, and PGE2and prevented by the B2antagonist HOE-140, but anti-IL-1β serum was ineffective. The results indicate that BK impairs human ASM cell responses to Iso, and the effect is largely mediated by B2receptor-related COX product release via both COX isoforms and is independent of IL-1β.

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TGF-β1 stimulates IL-8 release, COX-2 expression, and PGE2release in human airway smooth muscle cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2000.279.1.l201 ◽

2000 ◽

Vol 279 (1) ◽

pp. L201-L207 ◽

Cited By ~ 75

Author(s):

Choong Yi Fong ◽

Linhua Pang ◽

Elaine Holland ◽

Alan J. Knox

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Transforming Growth Factor ◽

Airway Smooth Muscle Cells ◽

Dependent Manner ◽

Human Airway Smooth Muscle ◽

Human Airway ◽

Cox Inhibitor ◽

Cox 2 ◽

Tgf Β1

We have recently shown that endogenous prostanoids are critical in bradykinin-stimulated interleukin (IL)-8 release from human airway smooth muscle (ASM) cells. In this study, we tested the ability of transforming growth factor (TGF)-β1 to stimulate IL-8 release, cyclooxygenase (COX)-2 expression and PGE2 generation in cultured human ASM cells and explored the role of COX products and COX-2 induction on IL-8 release. TGF-β1 stimulated IL-8 release, COX-2 induction, and PGE2 generation in a concentration- and time-dependent manner. Maximal IL-8 release was achieved with 10 ng/ml of TGF-β1 after 16 h of incubation, which was inhibited by the transcription inhibitor actinomycin D and the corticosteroid dexamethasone but was not affected by the nonselective COX inhibitor indomethacin and the selective COX-2 inhibitor NS-398 despite their inhibition on TGF-β1-induced PGE2 release. These results show for the first time that TGF-β1 stimulates IL-8 release, COX-2 induction, and PGE2 generation in human ASM cells and that PGE2 generation is not critical for TGF-β1-induced IL-8 release. These findings suggest that TGF-β1 may play an important role in the pathophysiology of asthma.

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Role of ERK MAP kinases in responses of cultured human airway smooth muscle cells to IL-1β

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1999.277.5.l943 ◽

1999 ◽

Vol 277 (5) ◽

pp. L943-L951 ◽

Cited By ~ 18

Author(s):

Johanne D. Laporte ◽

Paul E. Moore ◽

Joseph H. Abraham ◽

Geoffrey N. Maksym ◽

Ben Fabry ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Airway Smooth Muscle ◽

Muscle Cells ◽

Phospholipase A ◽

Airway Smooth Muscle Cells ◽

Dependent Manner ◽

Human Airway Smooth Muscle ◽

Human Airway ◽

Cox 2

We have previously reported that interleukin (IL)-1β causes β-adrenergic hyporesponsiveness in cultured human airway smooth muscle cells by increasing cyclooxygenase-2 (COX-2) expression and prostanoid formation. The purpose of this study was to determine whether extracellular signal-regulated kinases (ERKs) are involved in these events. Levels of phosphorylated ERK (p42 and p44) increased 8.3- and 13-fold, respectively, 15 min after treatment with IL-1β (20 ng/ml) alone. Pretreating cells with the mitogen-activated protein kinase kinase inhibitor PD-98059 or U-126 (2 h before IL-1β treatment) decreased ERK phosphorylation. IL-1β (20 ng/ml for 22 h) alone caused a marked induction of COX-2 and increased basal PGE2 release 28-fold ( P < 0.001). PD-98059 (100 μM) and U-126 (10 μM) each decreased COX-2 expression when administered before IL-1β treatment. In control cells, PD-98059 and U-126 had no effect on basal or arachidonic acid (AA; 10 μM)-stimulated PGE2 release, but both inhibitors caused a significant decrease in bradykinin (BK; 1 μM)-stimulated PGE2 release, consistent with a role for ERK in the activation of phospholipase A2 by BK. In IL-1β-treated cells, prior administration of PD-98059 caused 81, 92 and 40% decreases in basal and BK- and AA-stimulated PGE2 release, respectively ( P < 0.01), whereas administration of PD-98059 20 h after IL-1β resulted in only 38 and 43% decreases in basal and BK-stimulated PGE2release, respectively ( P < 0.02) and had no effect on AA-stimulated PGE2 release. IL-1β attenuated isoproterenol-induced decreases in human airway smooth muscle stiffness as measured by magnetic twisting cytometry, and PD-98059 or U-126 abolished this effect in a concentration-dependent manner. These results are consistent with the hypothesis that ERKs are involved early in the signal transduction pathway through which IL-1β induces PGE2 synthesis and β-adrenergic hyporesponsiveness and that ERKs act by inducing COX-2 and activating phospholipase A2.

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Prostanoids mediate IL-1β-induced β-adrenergic hyporesponsiveness in human airway smooth muscle cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1998.275.3.l491 ◽

1998 ◽

Vol 275 (3) ◽

pp. L491-L501 ◽

Cited By ~ 24

Author(s):

Johanne D. Laporte ◽

Paul E. Moore ◽

Reynold A. Panettieri ◽

Winfried Moeller ◽

Joachim Heyder ◽

...

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Cell Stiffness ◽

Airway Smooth Muscle Cells ◽

Human Airway Smooth Muscle ◽

Human Airway ◽

Heterologous Desensitization ◽

Cox 2 ◽

Inhibitor Of Protein Synthesis ◽

Induced Changes

We have previously reported that pretreatment of cultured human airway smooth muscle (HASM) cells with interleukin-1β (IL-1β) results in decreased β-adrenergic responsiveness. The purpose of this study was to determine whether prostanoids released as a result of cyclooxygenase-2 (COX-2) induction by IL-1β contribute to this effect of the cytokine. Confluent serum-deprived HASM cells were studied in passages 4–7. IL-1β (20 ng/ml for 22 h) reduced the ability of the β-agonist isoproterenol (Iso) to decrease stiffness of HASM cells as measured by magnetic twisting cytometry. The effect of IL-1β on Iso-induced changes in cell stiffness was abolished by nonselective [indomethacin (Indo), 10−6 M] and selective (NS-398, 10−5 M) COX-2 inhibitors. Indo and NS-398 also inhibited both the increased basal cAMP and the decreases in Iso-stimulated cAMP production induced by IL-1β. IL-1β (20 ng/ml for 22 h) caused an increase in both basal (15-fold) and arachidonic acid (AA)-stimulated (10-fold) PGE2 release. Indo blocked basal and AA-stimulated PGE2 release in both control and IL-1β-treated cells. NS-398 also markedly reduced basal and AA-stimulated PGE2release in IL-1β-treated cells but had no significant effect on AA-stimulated PGE2 release in control cells. Western blot analysis confirmed the induction of COX-2 by IL-1β. Exogenously administered PGE2(10−7 M, 22 h) caused a significant reduction in the ability of Iso to decrease cell stiffness, mimicking the effects of IL-1β. Cycloheximide (10 μg/ml for 24 h), an inhibitor of protein synthesis, also abolished the effects of IL-1β on Iso-induced cell stiffness changes and cAMP formation. In summary, our results indicate that IL-1β significantly increases prostanoid release by HASM cells as a result of increased COX-2 expression. The prostanoids appear to contribute to β-adrenergic hyporesponsiveness, perhaps by heterologous desensitization of the β2 receptor.

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Interleukin-6 family cytokines: signaling and effects in human airway smooth muscle cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.280.6.l1225 ◽

2001 ◽

Vol 280 (6) ◽

pp. L1225-L1232 ◽

Cited By ~ 24

Author(s):

Thomas Lahiri ◽

Johanne D. Laporte ◽

Paul E. Moore ◽

Reynold A. Panettieri ◽

Stephanie A. Shore

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Cell Types ◽

Oncostatin M ◽

Airway Smooth Muscle Cells ◽

Human Airway Smooth Muscle ◽

Human Airway ◽

Cox 2 ◽

Transcription 3 ◽

Dose Dependent

Interleukin (IL)-1β induces cyclooxygenase (COX)-2 expression and prostanoid formation in cultured human airway smooth muscle (HASM) cells. In other cell types, IL-6 family cytokines induce COX-2 or augment IL-1β-induced COX-2 expression. The purpose of this study was to determine whether IL-6 family cytokines were involved in COX-2 expression in HASM cells. RT-PCR was used to demonstrate that the necessary receptor components for IL-6-type cytokine binding are expressed in HASM cells. IL-6 and oncostatin M (OSM) each caused a dose-dependent phosphorylation of signal transducer and activator of transcription-3, whereas IL-11 did not. IL-6, IL-11, and OSM alone had no effect on COX-2 expression. However, OSM caused dose-dependent augmentation of COX-2 expression and prostaglandin (PG) E2release induced by IL-1β. In contrast, IL-6 and IL-11 did not alter IL-1β-induced COX-2 expression. IL-6 did increase IL-1β-induced PGE2formation in unstimulated cells but not in cells stimulated with arachidonic acid (AA; 10−5M), suggesting that IL-6 effects were mediated at the level of AA release. Our results indicate that IL-6 and OSM are capable of inducing signaling in HASM cells. In addition, OSM and IL-1β synergistically cause COX-2 expression and PGE2release.

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Thymic Stromal Lymphopoietin Receptor-Mediated IL-6 and CC/CXC Chemokines Expression in Human Airway Smooth Muscle Cells: Role of MAPKs (ERK1/2, p38, and JNK) and STAT3 Pathways

The Journal of Immunology ◽

10.4049/jimmunol.0902515 ◽

2010 ◽

Vol 184 (12) ◽

pp. 7134-7143 ◽

Cited By ~ 80

Author(s):

Lianyu Shan ◽

Naresh Singh Redhu ◽

Ali Saleh ◽

Andrew J. Halayko ◽

Jamila Chakir ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Airway Smooth Muscle ◽

Muscle Cells ◽

Thymic Stromal Lymphopoietin ◽

Airway Smooth Muscle Cells ◽

Human Airway Smooth Muscle ◽

Human Airway

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Role of C/EBP-Isoforms in IP-10 and IL-6 Production by Human Airway Smooth Muscle Cells.

10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a6317 ◽

2009 ◽

Author(s):

H Alkhouri ◽

M Roth ◽

B Oliver ◽

CL Armour ◽

JM Hughes

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Airway Smooth Muscle ◽

Muscle Cells ◽

Airway Smooth Muscle Cells ◽

Human Airway Smooth Muscle ◽

Human Airway

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Human Airway Smooth Muscle Cells Express the High Affinity Receptor for IgE (FcεRI): A Critical Role of FcεRI in Human Airway Smooth Muscle Cell Function

The Journal of Immunology ◽

10.4049/jimmunol.175.4.2613 ◽

2005 ◽

Vol 175 (4) ◽

pp. 2613-2621 ◽

Cited By ~ 59

Author(s):

Abdelilah Soussi Gounni ◽

Vincent Wellemans ◽

Jia Yang ◽

Fabienne Bellesort ◽

Kamrouz Kassiri ◽

...

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Cell Function ◽

Critical Role ◽

Airway Smooth Muscle Cell ◽

Airway Smooth Muscle Cells ◽

Human Airway Smooth Muscle ◽

Human Airway ◽

High Affinity Receptor

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Role of phospholipase C and tyrosine kinase systems in growth response of human airway smooth muscle cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1996.270.5.l795 ◽

1996 ◽

Vol 270 (5) ◽

pp. L795-L802 ◽

Cited By ~ 1

Author(s):

S. De ◽

E. T. Zelazny ◽

J. F. Souhrada ◽

M. Souhrada

Keyword(s):

Smooth Muscle ◽

Tyrosine Kinase ◽

Cell Count ◽

Phospholipase C ◽

Airway Smooth Muscle ◽

Thymidine Incorporation ◽

Airway Smooth Muscle Cells ◽

Dependent Manner ◽

Human Airway Smooth Muscle ◽

Human Airway

The primary culture of confluent human airway smooth muscle (ASM) cells were exposed up to 5 days to human recombinant interleukin (IL)-1 beta in the presence of indomethacin and 1% fetal bovine serum. The proliferation was assessed by a [3H]thymidine incorporation and direct cell count. We found that IL-1 beta significantly increased thymidine incorporation into and cell count of ASM cells in a concentration-dependent manner. Pretreatment of cells with specific polyclonal antibodies against platelet-derived growth factor (PDGF-BB homodimer) completely inhibited the IL-1 beta-induced increase in thymidine incorporation. The PDGF-BB, at the concentrations of 1.5 and 2.5 ng/ml, stimulated the proliferation of ASM cells. The proliferation action of IL-1 beta was potentiated when PDGF-BB was added into the medium in combination with IL-1 beta. Pretreatment of cells with genistein (0.37 microM), a specific tyrosine kinase inhibitor, attenuated the proliferative effect of IL-1 beta and PDGF-BB. To clarify whether these growth stimuli (IL-1 beta and PDGF-BB) activated phospholipase C (PLC), we examined the formation of phosphatidylinositols. We observed that both agents significantly increased phosphoinositide turnover. In contrast, genistein pretreatment (0.37 microM) prevented formation of inositol 1,4,5-trisphosphate (IP3), as induced by IL-1 beta and/or PDGF-BB. This study demonstrates that both IL-1 beta and PDGF-BB could induce proliferation of ASM cells through the activation of tyrosine kinase and PLC, which in turn stimulate the formation of IP3, a second messenger molecule.

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