The soluble interleukin 6 receptor (sIL-6R) circulates at elevated levels in various diseases. This suggests that inflammatory mediators control sIL-6R release. Through examination of human neutrophils, it was found that the acute phase reactant C-reactive protein (CRP) activates a threefold increase in sIL-6R production. Maximal release occurred after 30–60 min exposure to CRP (50 μg/ml), and was mimicked by peptides corresponding to amino acid residues 174– 185 and 201–206 of native CRP. A third peptide fragment (77–82) had no effect. Differential mRNA splicing did not account for the CRP-mediated release of sIL-6R, since this isoform was not detected in conditioned media. Furthermore, stimulation of neutrophils with CRP or with peptides 174–185 or 201–206 promoted a loss of membrane-bound IL-6R, suggesting release by proteolytic shedding. The metalloprotease inhibitor TAPI had only a marginal effect on CRP-mediated sIL-6R release, suggesting that shedding occurs via a mechanism distinct from that previously reported. It well established that IL-6 stimulates the acute phase expression of CRP. Our current findings demonstrate a novel relationship between these two mediators, since CRP may affect IL-6–mediated inflammatory events by enabling formation of the sIL-6R/IL-6 complex.
Skip Nav Destination
Article navigation
1 February 1999
Article Contents
Brief Definitive Report|
February 01 1999
C-reactive Protein: A Physiological Activator of Interleukin 6 Receptor Shedding
Simon A. Jones,
Simon A. Jones
From the *Department of Cell Biology and the ‡Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama 35294; the §Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel; the ‖Department of Microbiology, Tokyo Medical and Dental University, Tokyo 113, Japan
Search for other works by this author on:
Daniela Novick,
Daniela Novick
From the *Department of Cell Biology and the ‡Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama 35294; the §Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel; the ‖Department of Microbiology, Tokyo Medical and Dental University, Tokyo 113, Japan
Search for other works by this author on:
Sankichi Horiuchi,
Sankichi Horiuchi
From the *Department of Cell Biology and the ‡Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama 35294; the §Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel; the ‖Department of Microbiology, Tokyo Medical and Dental University, Tokyo 113, Japan
Search for other works by this author on:
Naoki Yamamoto,
Naoki Yamamoto
From the *Department of Cell Biology and the ‡Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama 35294; the §Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel; the ‖Department of Microbiology, Tokyo Medical and Dental University, Tokyo 113, Japan
Search for other works by this author on:
Alexander J. Szalai,
Alexander J. Szalai
From the *Department of Cell Biology and the ‡Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama 35294; the §Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel; the ‖Department of Microbiology, Tokyo Medical and Dental University, Tokyo 113, Japan
Search for other works by this author on:
Gerald M. Fuller
Gerald M. Fuller
From the *Department of Cell Biology and the ‡Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama 35294; the §Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel; the ‖Department of Microbiology, Tokyo Medical and Dental University, Tokyo 113, Japan
Search for other works by this author on:
Simon A. Jones
,
Daniela Novick
,
Sankichi Horiuchi
,
Naoki Yamamoto
,
Alexander J. Szalai
,
Gerald M. Fuller
From the *Department of Cell Biology and the ‡Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama 35294; the §Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel; the ‖Department of Microbiology, Tokyo Medical and Dental University, Tokyo 113, Japan
Address correspondence to Gerald M. Fuller, Department of Cell Biology, University of Alabama at Birmingham, Basic Health Science Bldg., 1918 University Blvd., Birmingham, AL 35294. Phone: 205-934-7596; Fax: 205-934-0950; E-mail: [email protected]
S.A. Jones's present address is School of Biosciences, University of Wales Cardiff, P.O. Box 911, Cardiff, CF1 3US, UK.
Received:
October 19 1998
Revision Received:
December 04 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (3): 599–604.
Article history
Received:
October 19 1998
Revision Received:
December 04 1998
Citation
Simon A. Jones, Daniela Novick, Sankichi Horiuchi, Naoki Yamamoto, Alexander J. Szalai, Gerald M. Fuller; C-reactive Protein: A Physiological Activator of Interleukin 6 Receptor Shedding . J Exp Med 1 February 1999; 189 (3): 599–604. doi: https://doi.org/10.1084/jem.189.3.599
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement
