Expression of Osteopontin in a Macrophage Cell Line and in Transgenic Mice with Pulmonary Fibrosis Resulting from the Lung Expression of a Tumor Necrosis Factor‐α Transgene

Abstract

The expression level of osteopontin (OPN) mRNA was found to be increased in a macrophage cell line in the presence of recombinant tumor necrosis factor-alpha (TNF-alpha). OPN mRNA level was also explored in the lungs of transgenic mice which were expressing TNF-alpha in type II pneumocytes, a condition leading to pulmonary alveolitis and progressive fibrosis. OPN mRNA was significantly increased in the lungs of these transgenic mice. In situ hybridization showed that it was localized mostly in alveolar macrophages. Since OPN can be induced in macrophages by TNF-alpha stimulation and since on the other hand osteopontin appears to decrease the level of nitric oxide synthase, and thus the production of nitric oxide, osteopontin might also indirectly have an antifibrotic effect. The role played by osteopontin in fibrotic lesions resulting from the release of TNF-alpha deserves further study, since it may be involved in the balance of opposite effects eventually leading to local tissue damage ending in fibrosis.

Butein blocks tumor necrosis factor α-induced interleukin 8 and matrix metalloproteinase 7 production by inhibiting p38 kinase and osteopontin mediated signaling events in HT-29 cells

“…As shown in Fig. 6B, OPN was significantly induced by TNF-α stimulation, as published elsewhere (Miyazaki et al, 1995). However, contrary to our expectation, regardless of the concentration, butein did not inhibit TNF-α-induced OPN expression.…”

Osteopontin expression in ductal adenocarcinomas and undifferentiated carcinomas of the pancreas

“…It was, therefore, suggested that macrophages are the main source of OPN, which is taken up secondarily by tumor cells [2]. In macrophages, the inflammatory cytokines interleukin-1 b and tumor necrosis factor-a appear to upregulate OPN expression [13]. Furthermore, OPN expression is elicited in response to pathological stimuli by various cell types, including endothelial cells, smooth-muscle cells [14], and T-lymphocytes [17], resulting in chemotaxis.…”

Osteopontin gene and clinical severity of multiple sclerosis

“…It is, however, also possible that the increased transcription rate seen in demyelinating disease may be a secondary event marking the established inflammatory process. For example, it is known that pro-inflammatory cytokines such as tumour necrosis factor and interleukin-1β or nitric oxide, which are elevated in multiple sclerosis, can induce osteopontin gene expression [9,14,16].…”