Macrophage-fibroblast interplay: a target for neuropeptide-based treatment of fibrotic disease?

Abstract

Background Fibrosis is defined as an excessive accumulation of extracellular matrix (ECM) components with an associated loss of normal tissue architecture and function. Fibrosis occurs in many different auto-inflammatory (auto-immune) diseases. Current therapies targeting fibrosis are limited and we are in great need for novel therapeutic regimens. In fibrosis, abnormal fibroblast proliferation and ECM production by fibroblasts is stimulated by factors released by different cell types, amongst which macrophages. Macrophages produce many pro-fibrotic factors, such as IL-6, CCL2, PDGF and TGF-beta. In rodent models of rheumatoid arthritis and inflammatory bowel disease, somatostatin analogues exerted strong anti-inflammatory effects, by inhibition of proinflammatory cytokine secretion. Somatostatin analogues bind to somatostatin receptors (sst) and we demonstrated sst subtype 2 expression on human macrophages. In the present study we investigated the effects of somatostatin, octreotide, a clinically used somatostatin analogue, and cortistatin, an endogenously expressed somatostatin-like peptide, on macrophage-induced fibroblast proliferation.