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Clinical and Diagnostic Laboratory Immunology, May 1998, p. 281-287, Vol. 5, No. 3
Department of Medicine, Wake Forest
University School of Medicine, Winston-Salem, North Carolina
Received 1 October 1997/Returned for modification 18 December
1997/Accepted 21 January 1998
Endotoxin (lipopolysaccharide [LPS]) is a potent activator of a
number of inflammatory genes in blood leukocytes,
including interleukin-1 (IL-1). Blood leukocytes isolated from patients with septic shock fail to produce IL-1 in response to LPS, a
phenomenon known as endotoxin tolerance. To study the regulation of
IL-1 expression in endotoxin-tolerant cells, the protein
phosphatase inhibitor okadaic acid was used to examine the effects of
protein phosphorylation on IL-1
1071-412X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Interleukin-1
Expression after Inhibition of
Protein Phosphatases in Endotoxin-Tolerant Cells
gene expression. We found that
endotoxin-tolerant cells produced normal levels of IL-1 when protein
phosphatases were inhibited. In the human pro-monocytic cell line
THP-1, okadaic acid increased mRNA accumulation and synthesis of
IL-1 protein. Normal and endotoxin-tolerant THP-1 cells accumulated
IL-1 mRNA and protein with similar delayed kinetics. Okadaic acid
stabilization of IL-1 mRNA appears to be the primary mechanism
through which endotoxin-tolerant cells accumulate IL-1 mRNA and
protein. Endotoxin-tolerant cells were unable to activate transcription
in response to okadaic acid. However, the transcription factor NF-
B,
which is known to be involved in IL-1 expression, was translocated
to the nucleus in both normal and endotoxin-tolerant cells after
treatment with okadaic acid. These studies revealed that protein
phosphorylation can affect gene expression on at least two distinct
levels, transcription factor activation and mRNA stability.
Endotoxin-tolerant cells have decreased transcription activation
potential, while IL-1 mRNA stability remains responsive to protein
phosphorylation.
*
Corresponding author. Mailing address: Department of
Medicine, Section on Infectious Diseases, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157. Phone: (336) 716-9397. Fax: (336) 716-7492. E-mail: byoza{at}wfubmc.edu.
Clinical and Diagnostic Laboratory Immunology, May 1998, p. 281-287, Vol. 5, No. 3
1071-412X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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