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Brief Definitive Report Hyaluronan Fragments Activate an NF-KB/I-KB(x

By Autoregulatory Loop, Murine Macrophages, Paulw Noble, Charlotte M. Mckee, Mary Cowmanfl and Hyun S. Shin


Macrophages play an important role in the acute tissue inflammatory response through the release of cytokines and growth factors in response to stimuli such as lipopolysaccharide (LPS). Macrophage inflammatory effector functions are also influenced by interactions with the extracellular matrix (ECM). Such macrophage-ECM interactions may be important in regulating chronic inflammatory responses. Recent evidence has suggested that hyaluronan (HA), a glycosaminoglycan (GAG) component of ECM can induce inflammatory gene expression in murine macrophages. HA exists in its native form as a large polymer, but is found as smaller fragments under inflammatory conditions. The NF-KB/I-KB transcriptional regulatory system has been shown to be a critical component of the host inflammatory response. We examined the effects of high molecular weight HA and lower molecular weight HA fragments on NF-KB activation in mouse macrophages. Only the smaller HA fragments were found to activate NF-kB DNA binding activity. After HA stimulation, I-KBot mRNA was induced and I-KBot protein levels, which initially decreased, were restored. The induction of I-KBot expression was not observed for other GAGs. The time course of I-KBa protein regeneration in response to HA fragments was consistent with an autoregulatory mechanism. In support of this mechanism, i

Year: 1996
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