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Transthyretin is an inhibitor of monocyte and endothelial cell interleukin-1 production

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Abstract

Human serurn was found to contain an inhibitor of constitutive interleukin 1 (IL-1) production by human umbilical vein endothelial cells (ECs). Purification of the serum activity by anion exchange chromatography, molecular sieve HPLC, and hydroxyl apatite chromntography yielded material 82% pure with a molecular weight of 17 kDa by SDS-PAGE. Amino acid sequencing revealed the purified inhibitor to be transthyretin (TTR). a liver-derived protein. There was a 42.6% reduction in the production of spontaneous IL-1 activity in EC supernatants after coculture with 10μg/ml TTR. TTR was subsequently found by ELISA to inhibit LPS-stimulated IL-1 production by cells of the human monocytic leukemia line THP-1 by 47.1 ± 9.4%, whereas a less striking but still significant inhibition of monocyte-derived IL-1β production was also observed. Inhibition of IL-1 secretion correlated with increased IL-1 mRNA synthesis in both THP-1 cells and monocytes. Furthermore, TTR was associated with increased intracellulaf concentrations of IL-1β. These data suggest that TTR functions by inhibiting processing of newly synthesized peptide for secretion. This novel inhibitory effect of TTR on the production of IL-1 activity suggests a previously unrecognized endogenous antiinflammatory mediator.

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Authors and Affiliations

  1. Department of Medicine National Jewish Center for Immunology and Respiratory Medicine, University of Colorado Health Sciences Center, 1400 Jackson St., 80206, Denver, Colorado

    Larry Borish, Michael S. King, James J. Mascali, Sylene Johnson, Brian Coll & Lanny J. Rosenwasser

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Borish, L., King, M.S., Mascali, J.J. et al. Transthyretin is an inhibitor of monocyte and endothelial cell interleukin-1 production. Inflammation 16, 471–484 (1992). https://doi.org/10.1007/BF00918973

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