| First Author | Luzina IG | Year | 2013 |
| Journal | Am J Respir Cell Mol Biol | Volume | 49 |
| Issue | 6 | Pages | 999-1008 |
| PubMed ID | 23837438 | Mgi Jnum | J:231563 |
| Mgi Id | MGI:5771753 | Doi | 10.1165/rcmb.2013-0093OC |
| Citation | Luzina IG, et al. (2013) Interleukin-33 potentiates bleomycin-induced lung injury. Am J Respir Cell Mol Biol 49(6):999-1008 |
| abstractText | The mechanisms of interstitial lung disease (ILD) remain incompletely understood, although recent observations have suggested an important contribution by IL-33. Substantial elevations in IL-33 expression were found in the lungs of patients with idiopathic pulmonary fibrosis and scleroderma lung disease, as well as in the bleomycin injury mouse model. Most of the observed IL-33 expression was intracellular and intranuclear, suggesting involvement of the full-length (fl) protein, but not of the proteolytically processed mature IL-33 cytokine. The effects of flIL-33 on mouse lungs were assessed independently and in combination with bleomycin injury, using recombinant adenovirus-mediated gene delivery. Bleomycin-induced changes were not affected by gene deficiency of the IL-33 receptor T1/ST2. Combined flIL-33 expression and bleomycin injury exerted a synergistic effect on pulmonary lymphocyte and collagen accumulation, which could be explained by synergistic regulation of the cytokines transforming growth factor-beta, IL-6, monocyte chemotactic protein-1, macrophage inflammatory protein\x{2013}1alpha, and tumor necrosis factor-alpha. By contrast, no increase in the levels of the Th2 cytokines IL-4, IL-5, or IL-13 was evident. Moreover, flIL-33 was found to increase the expression of several heat shock proteins (HSPs) significantly, and in particular HSP70, which is known to be associated with ILD. Thus, flIL-33 is a synergistic proinflammatory and profibrotic regulator that acts by stimulating the expression of several non-Th2 cytokines, and activates the expression of HSP70. |
