PGE2 Desensitizes β-Agonist Effect on Human Lung Fibroblast-Mediated Collagen Gel Contraction through Upregulating PDE4
In the current study, we investigated the effect of a long-acting β-agonist (salmeterol) and a phosphodiesterase 4 (PDE4) inhibitor (cilomilast) on human lung fibroblast-mediated collagen gel contraction. Higher concentrations of salmeterol (10−7 and 10−6 M) inhibited fibroblast-mediated collagen ge...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/145197 |
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| author | Qiuhong Fang Yingmin Ma Jing Wang Joel Michalski Stephen I. Rennard Xiangde Liu |
| author_facet | Qiuhong Fang Yingmin Ma Jing Wang Joel Michalski Stephen I. Rennard Xiangde Liu |
| author_sort | Qiuhong Fang |
| collection | DOAJ |
| description | In the current study, we investigated the effect of a long-acting β-agonist (salmeterol) and a phosphodiesterase 4 (PDE4) inhibitor (cilomilast) on human lung fibroblast-mediated collagen gel contraction. Higher concentrations of salmeterol (10−7 and 10−6 M) inhibited fibroblast-mediated collagen gel contraction. No effect was observed with cilomilast alone (up to 10−5 M). In the presence of 10−8 M salmeterol, however, cilomilast could significantly inhibit fibroblast-mediated collagen gel contraction in a concentration-dependent manner (10−7~10−5 M). Blockade of endogenous PGE2 by indomethacin further potentiated the inhibitory effect of salmeterol on fibroblast-mediated collagen gel contraction, but it did not affect cilomilast's effect. Pretreatment with PGE2 abolished the inhibitory effect of salmeterol, but it potentiated the inhibitory effect of cilomilast on fibroblast-mediated collagen gel contraction. Finally, indomethacin slightly inhibited PDE4C expression, while PGE2 stimulated the expression of PDE4A and -4C in human lung fibroblasts. These findings suggest that long-acting β-agonist and PDE4 inhibitor have a synergistic effect in regulating fibroblast tissue repair functions and that PGE2 can modulate the effect of β-agonist and PDE4 inhibitor at least in part through the mechanism of regulating PDE4 expression. |
| format | Article |
| id | doaj-art-ac922c30d521485daa0f2c5e332c6c3e |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-ac922c30d521485daa0f2c5e332c6c3e2025-02-03T07:25:45ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/145197145197PGE2 Desensitizes β-Agonist Effect on Human Lung Fibroblast-Mediated Collagen Gel Contraction through Upregulating PDE4Qiuhong Fang0Yingmin Ma1Jing Wang2Joel Michalski3Stephen I. Rennard4Xiangde Liu5Department of Pulmonary and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, ChinaDepartment of Pulmonary and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, ChinaDepartment of Pulmonary and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, ChinaPulmonary, Critical Care, Sleep and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5910, USAPulmonary, Critical Care, Sleep and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5910, USAPulmonary, Critical Care, Sleep and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5910, USAIn the current study, we investigated the effect of a long-acting β-agonist (salmeterol) and a phosphodiesterase 4 (PDE4) inhibitor (cilomilast) on human lung fibroblast-mediated collagen gel contraction. Higher concentrations of salmeterol (10−7 and 10−6 M) inhibited fibroblast-mediated collagen gel contraction. No effect was observed with cilomilast alone (up to 10−5 M). In the presence of 10−8 M salmeterol, however, cilomilast could significantly inhibit fibroblast-mediated collagen gel contraction in a concentration-dependent manner (10−7~10−5 M). Blockade of endogenous PGE2 by indomethacin further potentiated the inhibitory effect of salmeterol on fibroblast-mediated collagen gel contraction, but it did not affect cilomilast's effect. Pretreatment with PGE2 abolished the inhibitory effect of salmeterol, but it potentiated the inhibitory effect of cilomilast on fibroblast-mediated collagen gel contraction. Finally, indomethacin slightly inhibited PDE4C expression, while PGE2 stimulated the expression of PDE4A and -4C in human lung fibroblasts. These findings suggest that long-acting β-agonist and PDE4 inhibitor have a synergistic effect in regulating fibroblast tissue repair functions and that PGE2 can modulate the effect of β-agonist and PDE4 inhibitor at least in part through the mechanism of regulating PDE4 expression.http://dx.doi.org/10.1155/2013/145197 |
| spellingShingle | Qiuhong Fang Yingmin Ma Jing Wang Joel Michalski Stephen I. Rennard Xiangde Liu PGE2 Desensitizes β-Agonist Effect on Human Lung Fibroblast-Mediated Collagen Gel Contraction through Upregulating PDE4 Mediators of Inflammation |
| title | PGE2 Desensitizes β-Agonist Effect on Human Lung Fibroblast-Mediated Collagen Gel Contraction through Upregulating PDE4 |
| title_full | PGE2 Desensitizes β-Agonist Effect on Human Lung Fibroblast-Mediated Collagen Gel Contraction through Upregulating PDE4 |
| title_fullStr | PGE2 Desensitizes β-Agonist Effect on Human Lung Fibroblast-Mediated Collagen Gel Contraction through Upregulating PDE4 |
| title_full_unstemmed | PGE2 Desensitizes β-Agonist Effect on Human Lung Fibroblast-Mediated Collagen Gel Contraction through Upregulating PDE4 |
| title_short | PGE2 Desensitizes β-Agonist Effect on Human Lung Fibroblast-Mediated Collagen Gel Contraction through Upregulating PDE4 |
| title_sort | pge2 desensitizes β agonist effect on human lung fibroblast mediated collagen gel contraction through upregulating pde4 |
| url | http://dx.doi.org/10.1155/2013/145197 |
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