Chemokines in tissue fibrosis

Abstract

Fibrosis or scarring of diverse organs and tissues is considered as a pathologic consequence of a chronically altered wound healing response which is tightly linked to inflammation and angiogenesis. The recruitment of immune cells, local proliferation of fibroblasts and the consecutive accumulation of extracellular matrix proteins are common pathophysiological hallmarks of tissue fibrosis, irrespective of the organ involved. Chemokines, a family of chemotactic cytokines, appear to be central mediators of the initiation as well as progression of these biological processes. Traditionally chemokines have only been considered to play a critical role in orchestrating the influx of immune cells to sites of tissue injury. However, within the last years, further aspects of chemokine biology including fibroblast activation and angiogenesis have been deciphered in tissue fibrosis of many different organs. Interestingly, certain chemokines appear to mediate common effects in liver, kidney, lung, and skin of various animal models, while others mediate tissue specific effects. These aspects have to be kept in mind when extrapolating data of animal studies to early human trials. Nevertheless, the further understanding of chemokine effects in tissue fibrosis might be an attractive approach for identifying novel therapeutic targets in chronic organ damage associated with high morbidity and mortality. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.

Reproductive age-associated fibrosis in the stroma of the mammalian ovary

“…In addition, we examined the expression pattern of genes involved in immune cell recruitment. Ccl2 encodes monocyte chemoattractant protein 1, which recruits monocytes to sites of inflammation where they ultimately differentiate into macrophages, and Ccl5 is involved in general leukocyte and fibroblast recruitment (Mantovani, et al 2004, Sahin and Wasmuth 2013). Both Ccl2 and Ccl5 expression were significantly increased in ovaries from reproductively old mice relative to young counterparts (Figures 10D-E).…”

Circulating CXCL10 in cirrhotic portal hypertension might reflect systemic inflammation and predict ACLF and mortality

“…Therefore, their hepatic expression has been examined and discussed with great interest in many publications. 6,12,20 The majority of these focused on the role of CXCL10 in patients with hepatitis C virus infection and on therapy. 10,11,21,22 CXCL10 is released by, eg, hepatocytes, hepatic stellate cells and myofibroblasts and establishes via chemotaxis and T-cell migration an inflammatory and profibrogenic setting in the liver eventually resulting in fibrosis and cirrhosis.…”

The cytokines of pulmonary fibrosis: Much learned, much more to learn

“…A recent thoughtful report [188] has suggested a role for CCR2 as a mechanistic linker between epithelial injury, inflammatory response (especially from monocytes and macrophages), and fibrosis. It is important to keep in mind, especially from the drug development perspective, that CCR2 binds other ligands in addition to CCL2 [189].…”