IL-33 Mediates Lung Inflammation by the IL-6-Type Cytokine Oncostatin M

Abstract

The interleukin-1 family member IL-33 participates in both innate and adaptive T helper-2 immune cell responses in models of lung disease. The IL-6-type cytokine Oncostatin M (OSM) elevates lung inflammation, Th2-skewed cytokines, alternatively activated (M2) macrophages, and eosinophils in C57Bl/6 mice in vivo. Since OSM induces IL-33 expression, we here test the IL-33 function in OSM-mediated lung inflammation using IL-33-/- mice. Adenoviral OSM (AdOSM) markedly induced IL-33 mRNA and protein levels in wild-type animals while IL-33 was undetectable in IL-33-/- animals. AdOSM treatment showed recruitment of neutrophils, eosinophils, and elevated inflammatory chemokines (KC, eotaxin-1, MIP1a, and MIP1b), Th2 cytokines (IL-4/IL-5), and arginase-1 (M2 macrophage marker) whereas these responses were markedly diminished in IL-33-/- mice. AdOSM-induced IL-33 was unaffected by IL-6-/- deficiency. AdOSM also induced IL-33R+ ILC2 cells in the lung, while IL-6 (AdIL-6) overexpression did not. Flow-sorted ILC2 responded in vitro to IL-33 (but not OSM or IL-6 stimulation). Matrix remodelling genes col3A1, MMP-13, and TIMP-1 were also decreased in IL-33-/- mice. In vitro, IL-33 upregulated expression of OSM in the RAW264.7 macrophage cell line and in bone marrow-derived macrophages. Taken together, IL-33 is a critical mediator of OSM-driven, Th2-skewed, and M2-like responses in mouse lung inflammation and contributes in part through activation of ILC2 cells.

A crosstalk between type 2 innate lymphoid cells and alternative macrophages in lung development and lung diseases (Review)

“…Recruitment of neutrophils, eosinophils and inflammatory chemokines (KC, eotaxin-1, MIP1a and MIP1b), Th2 cytokines (IL-4/5), arginase-1 (M2 macrophage marker) and IL-33R+ ILC2s cells are significantly elevated in adenovirus Oncostatin M (OSM) mice, while these responses are significantly attenuated in IL-33-/- mice ( 113 ). In vitro , IL-33 upregulates OSM expression in RAW264.7 macrophage cells and bone marrow-derived macrophages ( 113 ). Thus, IL-33 is a key mediator of OSM-driven lung inflammation, induction of type 2 immune responses and M2 macrophages in mice, which contributes via activation of ILC2s ( 113 ).…”

“…In vitro , IL-33 upregulates OSM expression in RAW264.7 macrophage cells and bone marrow-derived macrophages ( 113 ). Thus, IL-33 is a key mediator of OSM-driven lung inflammation, induction of type 2 immune responses and M2 macrophages in mice, which contributes via activation of ILC2s ( 113 ).…”

Dexamethasone Attenuates Oncostatin M Production via Suppressing of PI3K/Akt/NF-κB Signaling in Neutrophil-like Differentiated HL-60 Cells

“…Subcutaneous injection of recombinant OSM led to skin inflammation in a murine model [ 13 ]. Botelho and colleagues [ 14 ] reported that overexpression of OSM resulted in lung inflammation in mice. Pothoven et al [ 10 ] reported that neutrophils are the main source of OSM in inflammatory diseases.…”

Exploring the oncostatin M (OSM) feed-forward signaling of glioblastoma via STAT3 in pan-cancer analysis

“…In turn, in the tumor microenvironment, OSM has been reported to positively regulate EMT [ 52 ], degradation of ECM [ 53 ] and cell-substrate detachment of tumor cells [ 54 ], thus leading to metastatic transformation. According to our correlation analysis between OSM expression and specific immune cell infiltration, we make a point that the OSM-induced chronic inflammation may be mainly contributed by macrophages and neutrophils [ 4 , 55 – 57 ]. The regulations of various cells including tumor cells by OSM are extensively studied [ 58 – 60 ], however, enough shreds of evidence are still needed to demonstrate the relationship between OSM and diverse immune cells and the mechanisms.…”