Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response
Lung fibrosis is characterized by abnormal accumulation of fibroblasts in the interstitium of the alveolar space. Two populations of myofibroblasts, distinguished by Thy1 expression, are detected in human and murine lungs. Accumulation of Thy1-negative (Thy1−) myofibroblasts was shown in the lungs o...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2015-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/942179 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832564660224655360 |
|---|---|
| author | Pazit Y. Cohen Raphael Breuer Philip Zisman Shulamit B. Wallach-Dayan |
| author_facet | Pazit Y. Cohen Raphael Breuer Philip Zisman Shulamit B. Wallach-Dayan |
| author_sort | Pazit Y. Cohen |
| collection | DOAJ |
| description | Lung fibrosis is characterized by abnormal accumulation of fibroblasts in the interstitium of the alveolar space. Two populations of myofibroblasts, distinguished by Thy1 expression, are detected in human and murine lungs. Accumulation of Thy1-negative (Thy1−) myofibroblasts was shown in the lungs of humans with idiopathic pulmonary fibrosis (IPF) and of bleomycin-treated mice. We aimed to identify genetic changes in lung myofibroblasts following Thy1 crosslinking and assess the impact of specific lung myofibroblast Thy1-deficiency, in vivo, in bleomycin-injured mouse lungs. Thy1 increased in mouse lung lymphocytes following bleomycin injury but decreased in myofibroblasts when fibrosis was at the highest point (14 days), as assessed by immunohistochemistry. Using gene chip analysis, we detected that myofibroblast Thy1 crosslinking mediates downregulation of genes promoting cell proliferation, survival, and differentiation, and reduces production of extracellular matrix (ECM) components, while concurrently mediating the upregulation of genes known to foster inflammation and immunological functions. Chimeric Thy1-deficient mice with Thy1+ lymphocytes and Thy1− myofibroblasts showed fibrosis similar to wild-type mice and an increased number of CD4/CD25 regulatory T cells, with a concomitant decrease in inflammation. Lung myofibroblasts downregulate Thy1 expression to increase their proliferation but to diminish the in vivo inflammatory milieu. Inflammation is not essential for evolution of fibrosis as was previously stated. |
| format | Article |
| id | doaj-art-0e4fd347295c43db80524e8cf1432bb1 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-0e4fd347295c43db80524e8cf1432bb12025-02-03T01:10:23ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/942179942179Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic ResponsePazit Y. Cohen0Raphael Breuer1Philip Zisman2Shulamit B. Wallach-Dayan3Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelLung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelLung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelLung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelLung fibrosis is characterized by abnormal accumulation of fibroblasts in the interstitium of the alveolar space. Two populations of myofibroblasts, distinguished by Thy1 expression, are detected in human and murine lungs. Accumulation of Thy1-negative (Thy1−) myofibroblasts was shown in the lungs of humans with idiopathic pulmonary fibrosis (IPF) and of bleomycin-treated mice. We aimed to identify genetic changes in lung myofibroblasts following Thy1 crosslinking and assess the impact of specific lung myofibroblast Thy1-deficiency, in vivo, in bleomycin-injured mouse lungs. Thy1 increased in mouse lung lymphocytes following bleomycin injury but decreased in myofibroblasts when fibrosis was at the highest point (14 days), as assessed by immunohistochemistry. Using gene chip analysis, we detected that myofibroblast Thy1 crosslinking mediates downregulation of genes promoting cell proliferation, survival, and differentiation, and reduces production of extracellular matrix (ECM) components, while concurrently mediating the upregulation of genes known to foster inflammation and immunological functions. Chimeric Thy1-deficient mice with Thy1+ lymphocytes and Thy1− myofibroblasts showed fibrosis similar to wild-type mice and an increased number of CD4/CD25 regulatory T cells, with a concomitant decrease in inflammation. Lung myofibroblasts downregulate Thy1 expression to increase their proliferation but to diminish the in vivo inflammatory milieu. Inflammation is not essential for evolution of fibrosis as was previously stated.http://dx.doi.org/10.1155/2015/942179 |
| spellingShingle | Pazit Y. Cohen Raphael Breuer Philip Zisman Shulamit B. Wallach-Dayan Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response Mediators of Inflammation |
| title | Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response |
| title_full | Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response |
| title_fullStr | Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response |
| title_full_unstemmed | Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response |
| title_short | Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response |
| title_sort | bleomycin treated chimeric thy1 deficient mice with thy1 deficient myofibroblasts and thy positive lymphocytes resolve inflammation without affecting the fibrotic response |
| url | http://dx.doi.org/10.1155/2015/942179 |
| work_keys_str_mv | AT pazitycohen bleomycintreatedchimericthy1deficientmicewiththy1deficientmyofibroblastsandthypositivelymphocytesresolveinflammationwithoutaffectingthefibroticresponse AT raphaelbreuer bleomycintreatedchimericthy1deficientmicewiththy1deficientmyofibroblastsandthypositivelymphocytesresolveinflammationwithoutaffectingthefibroticresponse AT philipzisman bleomycintreatedchimericthy1deficientmicewiththy1deficientmyofibroblastsandthypositivelymphocytesresolveinflammationwithoutaffectingthefibroticresponse AT shulamitbwallachdayan bleomycintreatedchimericthy1deficientmicewiththy1deficientmyofibroblastsandthypositivelymphocytesresolveinflammationwithoutaffectingthefibroticresponse |