Figure 5.

Fold change in the expression of enzymes involved in the formation of the tetrasaccharide linker and CS biosynthetic enzymes and core proteins upon macrophage polarization and RA. Using microarray data, we analyzed the expression of HS core protein and biosynthetic enzymes upon macrophage polarization in vitro with either IFNγ/LPS (M1) or IL-4/IL-13 (M2) or in RA. Genes marked in dark gray show minimal expression in macrophages in our experience. Genes upregulated in M1/RA compared with M2/healthy macrophages are marked in red (p<0.05) or pink (p>0.05), genes downregulated in M1/RA macrophages are marked in dark blue (p<0.05) or light blue (p>0.05) and genes that were not measured are marked with a dash (–). Mehraj,⁴⁰ Martinez F,⁴¹ Derlindanti,⁴² Yıldırım-Buharalıoğlu⁴³ compared human M1 and M2 macrophages by microarray. Jablonski⁴⁴ and Jiang⁴⁵ compared M1 and M2 macrophages by microarray from C57BL/6 or BALB/c mice, respectively. Martinez P⁴⁶ performed individual quantative polymerase chain reactions (qPCRs) for NDSTs and sulfotransferases in human M1 and M2 macrophages. Kang,⁴⁷ Yarilina,⁴⁸ and You⁴⁹ compared CD14+ cells freshly isolated from human RA synovial fluid to CD14+ monocyte-derived macrophages (MDM) from healthy donors. CS, chondroitin; RA, rheumatoid arthritis; HS, heparan sulfate; IFNγ, interferon-γ; LPS, lipopolysaccharide; IL, interleukin; NDST, N-deacetylase/N-sulfotransferase.