Bacterial lipopolysaccharide (endotoxin) enhances expression and secretion of beta 2 interferon by human fibroblasts.
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 and nonlymphoid tissues. Endotoxin, or bacterial lipopolysaccharide (LPS) preparations derived from the outer membrane of Escherichia coli or Salmonella typhimurium rapidly 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 microgram/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 bacteria by enhancing IFN-beta 2 production by the ubiquitous fibroblast.
Helfgott
D C
DC
Rockefeller University, New York 10021.
May
L T
LT
Sthoeger
Z
Z
Tamm
I
I
Sehgal
P B
PB
D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli; D005347:Fibroblasts / Q000378:metabolism* / Q000382:microbiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007370:Interferon Type I / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
D007370:Interferon Type I; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D003513:Cycloheximide; D011493:Protein Kinase C