Alternatively activated macrophages differentially express fibronectin andits splice variants and the extracellular matrix protein beta IG-H3

Alternative activation of macrophages, induced by Th-2 cytokines and glucoc orticoids, is essential for the proper functioning of anti-inflammatory imm une reactions. To this end, alternatively activated macrophages (aaM Phi) e xpress a not yet fully unravelled set of genes including cytokines such as alternative macrophage activation-associated CC-chemokine (AMAC)-1 and patt ern recognition molecules such as the scavenger receptor CD163. In order to further characterize the molecular repertoire of aaM Phi, differential gen e expression was analyzed by combining subtractive suppression cloning and differential hybridization. We show here that aaM Phi induced by interleuki n (IL)-4 overexpress the prototype extracellular matrix (ECM) protein fibro nectin on the mRNA and protein level. This overall increase is accompanied by a shift in fibronectin splice variants from an embryonic to a mature pat tern. In addition, the expression of another ECM protein, beta IG-H3, is al so 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 suppre ssive effect on fibronectin and beta IG-H3 expression. In conclusion, overe xpression of ECM proteins induced by IL-4 in macrophages suggests that aaM Phi may be involved in ECM deposition and tissue remodelling during the hea ling phase of acute inflammatory reactions and in chronic inflammatory dise ases.