title: Type I interferon induces CX3CL1 (fractalkine) and CCL5 (RANTES) production in human pulmonary vascular endothelial cells.
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.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakano
authors.forename: T
authors.initials: T
authors.lastname: Fujii
authors.forename: M
authors.initials: M
authors.lastname: Hashimoto
authors.forename: N
authors.initials: N
authors.lastname: Yukawa
authors.forename: H
authors.initials: H
authors.lastname: Yoshifuji
authors.forename: K
authors.initials: K
authors.lastname: Ohmura
authors.forename: A
authors.initials: A
authors.lastname: Nakaizumi
authors.forename: T
authors.initials: T
authors.lastname: Mimori
mesh_terms: D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D054428:Chemokine CX3CL1 / Q000096:biosynthesis*; D003240:Connective Tissue Diseases / Q000276:immunology / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000276:immunology* / Q000473:pathology; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D016899:Interferon-beta / Q000008:administration & dosage / Q000009:adverse effects*; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D008856:Microscopy, Fluorescence
chemical_list: D018946:Chemokine CCL5; D054428:Chemokine CX3CL1; D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D016899:Interferon-beta; D053612:Janus Kinases