| First Author | Pluangnooch P | Year | 2024 |
| Journal | Respir Investig | Volume | 62 |
| Issue | 1 | Pages | 90-97 |
| PubMed ID | 38007853 | Mgi Jnum | J:355568 |
| Mgi Id | MGI:7719096 | Doi | 10.1016/j.resinv.2023.10.005 |
| Citation | Pluangnooch P, et al. (2024) Expression of constitutively active TbetaRI leads to attenuation of ovalbumin-induced allergic airway inflammation associated with augmented M2 polarization of alveolar macrophage. Respir Investig 62(1):90-97 |
| abstractText | BACKGROUND: Transforming growth factor-beta (Tgf-beta) plays an important role in the pathogenesis of asthma through the regulation of T cells and airway epithelium. Its functions in alveolar macrophage (AM) during allergic airway inflammation remain unknown. METHODS: A murine asthma model was induced with ovalbumin (ova) in TbetaRI(CA)/Fsp1-Cre transgenic mice expressing constitutively active Tgf-beta receptor type I (TbetaRI(CA)) under the control of Fsp1-Cre transgene. Cells in the bronchoalveolar lavage (BAL) were collected to study immune cell infiltration in the lungs. Cytokine levels in BAL fluid were measured by enzyme-linked immunoassay (ELISA). Lungs were sectioned and stained with hematoxylin and eosin, periodic acid-Schiff, and trichrome for histopathologic evaluation. AMs were assessed by flow cytometry and were sorted for quantitative polymerase chain reaction analysis. RESULTS: Our data indicated that TbetaRI(CA) transcripts were induced in AMs of TbetaRI(CA)/Fsp1-Cre mice. Following the ova challenges, TbetaRI(CA)/Fsp1-Cre mice exhibited reduced cellular infiltration of the airway, reduced pulmonary fibrosis, and reduced bronchial mucus secretion as compared to ova-challenged wild-type mice. An alternatively activated macrophage (M2) polarization was significantly elevated in the lungs of ova-challenged TbetaRI(CA)/Fsp1-Cre mice as reflected by increased numbers of AMs expressing M2 subtype marker, CD163, in the lungs and enhanced expression of CCR2 and CD206 in AMs. Moreover, TbetaRI(CA)/Fsp1-Cre AMs showed augmented expression of transcription factors, Foxo1, and IRF4, which are known to be positive regulators for M2 polarization. CONCLUSIONS: Expression of TbetaRI(CA) in AMs promoted M2 polarization and ameliorated allergic airway inflammation in an ova-induced asthma mouse model. |
