Alternatively activated macrophages differentially express fibronectin and its splice variants and the extracellular matrix protein βIG-H3

Alternative activation of macrophages, induced by Th-2 cytokines and glucocorticoids, is essential for the proper functioning of anti-inflammatory immune reactions. To this end, alternatively activated macrophages (aaM Phi) express a not yet fully unravelled set of genes including cytokines such as alternative macrophage activation-associated CC-chemokine (AMAC)-1 and pattern recognition molecules such as the scavenger receptor CD163. In order to further characterize the molecular repertoire of aaM Phi, differential gene expression was analyzed by combining subtractive suppression cloning and differential hybridization. We show here that aaM Phi induced by interleukin (IL)-4 overexpress the prototype extracellular matrix (ECM) protein fibronectin on the mRNA and protein level. This overall increase is accompanied by a shift in fibronectin splice variants from an embryonic to a mature pattern. In addition, the expression of another ECM protein, beta IG-H3, is also upregulated by IL-4 in aaM Phi. In contrast to IL-4 and in line with its inhibitory effect on wound healing, dexamethasone exerts a strongly suppressive effect on fibronectin and beta IG-H3 expression. In conclusion, overexpression of ECM proteins induced by IL-4 in macrophages suggests that aaM Phi may be involved in ECM deposition and tissue remodelling during the healing phase of acute inflammatory reactions and in chronic inflammatory diseases.