TNFalpha and IL-4 regulation of hyaluronan binding to monocyte CD44 involves posttranslational modification of CD44.

Journal Article (Journal Article)

Our previous studies have identified TNFalpha as a positive regulator and IL-4 as a negative regulator of human monocyte CD44-HA binding. In order to determine the mechanisms of IL-4- and TNFalpha-mediated regulation of monocyte HA binding, we measured HA binding and CD44 expression on peripheral blood monocytes following monocyte treatment with TNFalpha or IL-4, as well as following monocyte treatment with inhibitors of protein synthesis, N- and O-linked glycosylation, and chondroitin sulfation. IL-4 decreased CD44-HA binding on monocytes initially treated with TNFalpha. Similarly, pretreatment of monocytes with IL-4 prevented subsequent TNFalpha-mediated HA binding. Cycloheximide (protein synthesis inhibitor), tunicamycin (N-linked glycosylation inhibitor), and beta-d-xyloside (chondroitin sulfation inhibitor) all inhibited IL-4-mediated downregulation of TNFalpha-induced monocyte HA binding. Western blot analysis of CD44 from TNFalpha-treated monocytes revealed a 5-10 Mr decrease in the standard isoform of CD44. In contrast, IL-4 treatment of monocytes inhibited CD44-HA binding and reversed the 5- to 10-kDa decrease in monocyte CD44 Mr. Finally, studies with F10.44.2, a CD44 mab that enhances CD44-HA binding, indicated that IL-4 treatment of monocytes not only diminished constitutive HA binding, but also diminished CD44 mab-induced HA binding. Taken together, these data suggested that IL-4-mediated inhibition of TNFalpha-induced monocyte HA binding was dependent not only on protein synthesis, but also on N-linked glycosylation and chondroitin-sulfate modification of either CD44 or, alternatively, another monocyte protein(s) that may regulate the ability of CD44 to bind HA.

Full Text

Duke Authors

Cited Authors

  • Levesque, MC; Haynes, BF

Published Date

  • May 1, 1999

Published In

Volume / Issue

  • 193 / 2

Start / End Page

  • 209 - 218

PubMed ID

  • 10222064

International Standard Serial Number (ISSN)

  • 0008-8749

Digital Object Identifier (DOI)

  • 10.1006/cimm.1999.1456


  • eng

Conference Location

  • Netherlands