Oncostatin M stimulates proliferation, induces collagen production and inhibits apoptosis of human lung fibroblasts

Abstract

6JJ1 Oncostatin M (OSM), a member of the interleukin-6 (IL-6) cytokine family, acts on a variety of cells and elicits diversi®ed biological responses, suggesting potential roles in the regulation of cell survival, di erentiation and proliferation. 2 We have examined the e ect of OSM on the regulation of human lung ®broblast proliferation, collagen production and spontaneous apoptosis. The proliferative e ects of OSM (0.5 ± 100 ng ml 71 ) were assessed using a MTS assay as well as [ 3 H]-thymidine incorporation and cell counts at 24 and 48 h. Hydroxyproline was measured as an index of procollagen production by high pressure liquid chromotography (HPLC). Apoptosis was determined by annexin staining. 3 OSM enhanced the mitotic activity of lung ®broblasts in a time and dose dependent manner. Maximum proliferation of 57% above control was observed after incubation for 48 h with 2 ng ml 71 OSM (P50.05). 4 Incubation with the mitogen activated protein kinase (MAPK) kinase inhibitor, PD98059 or the tyrosine kinase inhibitor, genestein both signi®cantly reduced the mitogenic e ect of OSM (P50.05). 5 In contrast, proliferation in response to OSM was not regulated by induction of cyclo-oxygenase and subsequent prostaglandin E 2 (PGE 2 ) release or by IL-6. 6 OSM also stimulated ®broblasts to synthesize pro-collagen by a maximum of 35% above control levels after 48 h (P50.05). 7 OSM signi®cantly inhibited the spontaneous apoptosis of ®broblasts at 24 and 48 h. 8 These results provide evidence that OSM has pro-®brotic properties and suggest that it may play a role in normal lung wound repair and ®brosis.

Identification of Oncostatin M as a STAT5-Dependent Mediator of Bone Marrow Remodeling in KIT D816V-Positive Systemic Mastocytosis

“…OSM has been reported to promote proliferation of mesenchymal cells 25,26 and thus may be important for the bone marrow alterations associated with systemic mastocytosis. Therefore, we next wished to determine whether OSM derived from KIT D816V ϩ neoplastic cells can stimulate growth of mesenchymal cells.…”

“…24 Later, OSM was shown to act as a growth factor for mesenchymal cells, including endothelial cells, fibroblasts, and osteoblasts. [25][26][27][28] Recently, OSM has been implicated as an important cytokine in hematopoiesis. Transplantation experiments with OSM-deficient mice have shown that OSM stimulates stromal cells as well as hematopoietic progenitors and is required for the generation and maintenance of a proper microenvironment in the bone marrow.…”

Occurrence of an activated, profibrotic pattern of gene expression in lung CD8+ T cells from scleroderma patients

“…The gene with the greatest increase in expression in the array analyses was oncostatin M ( Figure 3D). Oncostatin M, a growth factor produced by activated T cells (63), stimulates collagen production and fibroblast proliferation (64). To confirm the increased expression of the oncostatin M gene, oncostatin M protein was measured in BAL fluid from patients with and without lung inflammation as well as from healthy controls.…”

Monocyte‐dependent oncostatin M and TNF‐α synergize to stimulate unopposed matrix metalloproteinase‐1/3 secretion from human lung fibroblasts in tuberculosis

“…OSM is a multi-functional cytokine secreted by monocytes and T cells. It is pro-angiogenic [19], modulates growth and differentiation in normal fibroblasts [20] and some malignant cells [21], and stimulates production of acute-phase response proteins in hepatocytes [22]. OSM is secreted on LPS stimulation of mononuclear and dendritic cells, [23] both of which are important cellular effectors of a protective immune response to Mtb.…”