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Interleukin-1β induces hyaluronan and CD44-dependent cell protrusions that facilitate fibroblast-monocyte binding

Meran, Soma, Martin, John, Luo, Dong Dong, Steadman, Robert and Phillips, Aled Owain 2013. Interleukin-1β induces hyaluronan and CD44-dependent cell protrusions that facilitate fibroblast-monocyte binding. American Journal of Pathology 182 (6) , pp. 2223-2240. 10.1016/j.ajpath.2013.02.038

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Persistent inflammation is a well-known determinant of progressive tissue fibrosis; however, the mechanisms underlying this process remain unclear. There is growing evidence indicating a role of the cytokine IL-1β in profibrotic responses. We previously demonstrated that fibroblasts stimulated with IL-1β increased their generation of the polysaccharide hyaluronan (HA) and increased their expression of the HA synthase enzyme (HAS-2). The aim of this study was to determine the significance of IL-1β–induced changes in HA and HAS-2 generation. In this study, we found that stimulation of fibroblasts with IL-1β results in the relocalization of HA associated with the cell to the outer cell membrane, where it forms HAS2- and CD44-dependent cell membrane protrusions. CD44 is concentrated within the membrane protrusions, where it co-localizes with the intracellular adhesion molecule 1. Furthermore, we have identified that these cell protrusions enhance IL-1β–dependent fibroblast-monocyte binding through MAPK/ERK signaling. Although previous data have indicated the importance of the HA-binding protein TSG-6 in maintaining the transforming growth factor β1–dependent HA coat, TSG-6 was not essential for the formation of the IL-1β–dependent HA protrusions, thus identifying it as a key difference between IL-1β– and transforming growth factor β1–dependent HA matrices. In summary, these data suggest that IL-1β–dependent HA generation plays a role in fibroblast immune activation, leading to sequestration of monocytes within inflamed tissue and providing a possible mechanism for perpetual inflammation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RB Pathology
Publisher: American Society for Investigative Pathology
ISSN: 0002-9440
Last Modified: 12 Jun 2019 02:11

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