Bacterial lipopolysaccharide (endotoxin) enhances expression and secretion of beta 2 interferon by human fibroblasts.

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Abstract
The human .beta.2 interferon (IFN-.beta.2) gene, a gene that also codes for B cell differentiation factor 2 (BSF-2), plasmacytoma/hybridoma growth factor (HGF), and hepatocyte-stimulating factor (HSF), is expressed in a variety of lymphoid an nonlymphoid tissues. Endotoxin, or bacterial lipopolysaccharide (LPS) preparations derived from the outer membrane of Escherichia coli or Salmonella typhimurium rapid elevate IFN-.beta.2 mRNA level in human skin fibroblasts (FS-4 strain). E. coli-derived LPS enhances IFN-.beta.2 mRNA expression in FS-4 fibroblasts at a concentration as low as 0.3 ng/ml; this response is near-maximal in the range of 0.1-1 .mu.g/ml LPS. The increase in IFN-.beta.2 mRNA level caused by LPS in FS-4 cells is detected within 30 min after addition of LPS, is sustained for at least 20 h thereafter, appears to involve the protein kinase C signal transduction pathway, does not require new protein synthesis, and is inhibited by dexamethasone in a dose-dependent fashion (in the range 10-6-10-8 M). Cultures of LPS-treated FS-4 cells exhibit an antiviral state against vesicular stomatitis virus, which can be prevented by anti-IFN-.beta. antiserum. Medium obtained from LPS-treated FS-4 cell cultures enhances the number of immunoglobulin-secreting cells in cultures of human B-lymphoblastoid (CESS) cells. Thus, LPS may trigger a number of host defense mechanisms in the course of infection due to Gram-negative bactria by enhancing IFN-.beta.2 production by the ubiquitous fibroblast.