Regulation of IL-33 by Oncostatin M in Mouse Lung Epithelial Cells

Abstract

IL-33 modulates both innate and adaptive immune responses at tissue sites including lung and may play critical roles in inflammatory lung disease. Although IL-33 expression can be altered upon NF-Kappa B activation, here we examine regulation by Oncostatin M, a gp130 cytokine family member, in mouse lung tissue. Responses were assessed in BALB/c mouse lung at day 7 of transient overexpression using endotracheally administered adenovirus encoding OSM (AdOSM) or empty vector (AdDel70). Whole lung extracts showed induction of IL-33 mRNA (>20-fold) and protein (10-fold increase in immunoblots) by AdOSM relative to AdDel70. Immunohistochemistry for IL-33 indicated a marked induction of nuclear staining in alveolar epithelial cells in vivo. Oncostatin M stimulated IL-33 mRNA and IL-33 full length protein in C10 mouse type 2 alveolar epithelial cells in culture in time-dependent and dose-dependent fashion, whereas IL-6, LIF, IL-31, IL-4, or IL-13 did not, and TGFβ repressed IL-33. IL-33 induction was associated with activation of STAT3, and pharmacological inhibition of STAT3 ameliorated IL-33 levels. These results indicate Oncostatin M as a potent inducer of IL-33 in mouse lung epithelial cells and suggest that an OSM/IL-33 axis may participate in innate immunity and inflammatory conditions in lung.

Oncostatin M expression in the mouse uterus during early pregnancy promotes embryo implantation and decidualization

“…3A). Il-33, a member of Il-1 family, is shown to be essential for mouse embryo implantation and induced in lung epithelial cells by Osm [22,23]. When cultured uterine epithelial cells were treated with Osm, both Il-33 and Osmr mRNA expressions were extremely stimulated ( Fig.…”

“…However, p-Stat3 and integrin b3 are key mediators for mouse implantation [20,21]. Il-33, a member of Il-1 family, is shown to be essential for mouse embryo implantation and induced in lung epithelial cells by Osm [22,23]. 3A).…”

Oncostatin M in the Regulation of Connective Tissue Cells and Macrophages in Pulmonary Disease

“…This suggests that OSM acts on the specific type II OSM receptor in these cells, since LIF (functions at the LIFR or Type I OSM receptor) had little effect. A series of more recent studies in mouse systems have shown that OSM can regulate the alarmin IL-33 in mouse type II alveolar epithelial cells in vitro and in vivo [68], and induces liver endothelial cells to express IL-33 [69]. In the lung, columnar epithelial cell have been shown to express IL-33, but may not respond directly to OSM with IL-33 induction [68].…”

“…A series of more recent studies in mouse systems have shown that OSM can regulate the alarmin IL-33 in mouse type II alveolar epithelial cells in vitro and in vivo [68], and induces liver endothelial cells to express IL-33 [69]. In the lung, columnar epithelial cell have been shown to express IL-33, but may not respond directly to OSM with IL-33 induction [68]. Since type II alveolar epithelial cells respond robustly to OSM in vitro, or to overexpression of OSM in vivo [68], whereas columnar epithelial cells did not, this may suggest STAT3 activation is not sufficient by itself to induce IL-33 in vivo.…”

“…In the lung, columnar epithelial cell have been shown to express IL-33, but may not respond directly to OSM with IL-33 induction [68]. Since type II alveolar epithelial cells respond robustly to OSM in vitro, or to overexpression of OSM in vivo [68], whereas columnar epithelial cells did not, this may suggest STAT3 activation is not sufficient by itself to induce IL-33 in vivo. Further work is required to determine if OSM regulates IL-33 in human lung epithelial cells or pulmonary endothelial cells.…”