title: Interleukin-1β-induced Reduction of CD44 Ser-325 Phosphorylation in Human Epidermal Keratinocytes Promotes CD44 Homomeric Complexes, Binding to Ezrin, and Extended, Monocyte-adhesive Hyaluronan Coats.
abstract: The proinflammatory cytokine interleukin-1β (IL-1β) attracts leukocytes to sites of inflammation. One of the recruitment mechanisms involves the formation of extended, hyaluronan-rich pericellular coats on local fibroblasts, endothelial cells, and epithelial cells. In the present work, we studied how IL-1β turns on the monocyte adhesion of the hyaluronan coat on human keratinocytes. IL-1β did not influence hyaluronan synthesis or increase the amount of pericellular hyaluronan in these cells. Instead, we found that the increase in the hyaluronan-dependent monocyte binding was associated with the CD44 of the keratinocytes. Although IL-1β caused a small increase in the total amount of CD44, a more marked impact was the decrease of CD44 phosphorylation at serine 325. At the same time, IL-1β increased the association of CD44 with ezrin and complex formation of CD44 with itself. Treatment of keratinocyte cultures with KN93, an inhibitor of calmodulin kinase 2, known to phosphorylate Ser-325 in CD44, caused similar effects as IL-1β (i.e. homomerization of CD44 and its association with ezrin) and resulted in increased monocyte binding to keratinocytes in a hyaluronan-dependent way. Overexpression of wild type CD44 standard form, but not a corresponding CD44 mutant mimicking the Ser-325-phosphorylated form, was able to induce monocyte binding to keratinocytes. In conclusion, treatment of human keratinocytes with IL-1β changes the structure of their hyaluronan coat by influencing the amount, post-translational modification, and cytoskeletal association of CD44, thus enhancing monocyte retention on keratinocytes.
authors: From the Institute of Biomedicine, Department of Medicine, University of Eastern Finland, Yliopistonranta 1E, P.O. Box 1627, 70211 Kuopio, Finland.
authors: Tiina
authors: T
authors: Jokela
authors: From the Institute of Biomedicine, Department of Medicine, University of Eastern Finland, Yliopistonranta 1E, P.O. Box 1627, 70211 Kuopio, Finland sanna.oikari@uef.fi.
authors: Sanna
authors: S
authors: Oikari
authors: From the Institute of Biomedicine, Department of Medicine, University of Eastern Finland, Yliopistonranta 1E, P.O. Box 1627, 70211 Kuopio, Finland.
authors: Piia
authors: P
authors: Takabe
authors: From the Institute of Biomedicine, Department of Medicine, University of Eastern Finland, Yliopistonranta 1E, P.O. Box 1627, 70211 Kuopio, Finland.
authors: Kirsi
authors: K
authors: Rilla
authors: From the Institute of Biomedicine, Department of Medicine, University of Eastern Finland, Yliopistonranta 1E, P.O. Box 1627, 70211 Kuopio, Finland.
authors: Riikka
authors: R
authors: Kärnä
authors: From the Institute of Biomedicine, Department of Medicine, University of Eastern Finland, Yliopistonranta 1E, P.O. Box 1627, 70211 Kuopio, Finland.
authors: Markku
authors: M
authors: Tammi
authors: From the Institute of Biomedicine, Department of Medicine, University of Eastern Finland, Yliopistonranta 1E, P.O. Box 1627, 70211 Kuopio, Finland.
authors: Raija
authors: R
authors: Tammi
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D005091:Exons; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000737:chemistry; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology*; D007962:Leukocytes / Q000166:cytology; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000166:cytology; D010766:Phosphorylation; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D012694:Serine / Q000737:chemistry*; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D053583:Interleukin-1beta; D012694:Serine; D000099149:Ezrin
keywords: CD44; Hyaluronan; Inflammation; Interleukin-1 (IL-1); Keratinocyte