Figure 6

Internalization and biological effects of acid-labile N -(2-hydroxypropyl)methacrylamide copolymer-dexamethasone conjugate in cultured human cells. Confocal images show the internalization and lysosomal localization of FITC-labeled acid-labile N-(2-hydroxypropyl)methacrylamide copolymer-dexamethasone conjugate (P-Dex) by (a) cultured human monocytes and (b) fibroblasts. In the human monocyte cultures, the internalized P-Dex represses lipopolysaccharide (LPS)-mediated production of (c) TNFα and (d) IL-6 to levels comparable with those found with free dexamethasone (Dex) (n = 3, P < 0.0002). (e) In synovial fibroblasts from a rheumatoid arthritis patient, P-Dex suppresses TNFα-induced expression of matrix metalloproteinases (MMP1 & MMP3) mRNA. (f) Human monocyte apoptosis was detected in untreated monocytes (upper left panel), and was greatly increased after serum withdrawal for 24 hours (upper right panel). Neither Dex (lower left) nor P-Dex (lower right) increased apoptosis above basal levels.