Type I interferon induces CX3CL1 (fractalkine) and CCL5 (RANTES) production in human pulmonary vascular endothelial cells

M Nakano,N Yukawa,A Nakaizumi,K Ohmura,H Yoshifuji,M Hashimoto,T Fujii,T Mimori

doi:10.1111/j.1365-2249.2012.04638.x

Abstract

Type I interferon (IFN) medications cause various adverse reactions, including vascular diseases. Although an association between chemokines and vascular diseases has also been reported, the relationship between type I IFN and chemokines in vascular endothelial cells (VEC) remains unclear. To provide clues to pathogenesis of the diseases, we analysed the effects of type I IFN on chemokine production in human VEC. Type I IFN induced higher CX3CL1 (fractalkine) mRNA expression and protein secretion in pulmonary arterial VEC than in umbilical vein VEC. Type I IFN also induced CCL5 [regulated upon activation normal T cell expressed and secreted (RANTES)] production in VEC, especially in lung micro-VEC. IFN-β induced much higher chemokine production than IFN-α, and Janus protein tyrosine kinase (JAK) inhibitor I prevented type I IFN-induced chemokine secretion. Type I IFN-induced chemokines may be involved in the pathophysiology of pulmonary vascular diseases, and the JAK inhibitor may serve as a therapeutic option for these diseases.

Highlights

Type I interferon (IFN) has been used as a therapeutic drug for the treatment of various diseases [1]; type I IFN-induced adverse reactions, including the development of connective tissue diseases (CTD), have been reported [2]
Increased chemokine levels have been reported in patients with vascular diseases; expression of CCL2 (MCP-1) [7], CCL5 [regulated upon activation normal T cell expressed and secreted (RANTES)] [8] and CX3CL1 [9] is augmented in Pulmonary arterial hypertension (PAH) patients
0·1 1 10 IFN-β nificant changes were observed in CCL2 secretion (Fig. 1c); we focused on CX3CL1 and CCL5

Summary

Introduction

Type I interferon (IFN) has been used as a therapeutic drug for the treatment of various diseases [1]; type I IFN-induced adverse reactions, including the development of connective tissue diseases (CTD), have been reported [2]. Type I IFN has been reported to be a probable pathogenic factor in CTD, such as systemic lupus erythematosus (SLE) [3] and systemic sclerosis (SSc), through vascular pathology [4]. Pulmonary arterial hypertension (PAH) is a severe vascular disease that develops in patients with CTD and has a high mortality rate. Increased chemokine levels have been reported in patients with vascular diseases; expression of CCL2 (MCP-1) [7], CCL5 [regulated upon activation normal T cell expressed and secreted (RANTES)] [8] and CX3CL1 (fractalkine) [9] is augmented in PAH patients. Increased leucocyte migration promoted by these chemokines may enhance inflammation and be involved in the development of vascular disorders

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Conclusion