To examine the ability of interleukin‐17A (IL‐17A) to stimulate angiogenesis, cell migration, and cytoskeletal rearrangement.

The effect of IL‐17A on microvascular tube formation and extracellular matrix invasion by human dermal endothelial cells (HDECs) was assessed using Matrigel matrix and Transwell Matrigel invasion chambers. IL‐17A–induced growth‐related oncogene α (GROα) and monocyte chemotactic protein 1 (MCP‐1) production in rheumatoid arthritis synovial fibroblasts (RASFs) and HDECs was measured by enzyme‐linked immunosorbent assay. IL‐17A–induced migration was assessed using peripheral blood mononuclear cell (PBMC) migration assays and wound‐repair scratch assays, with or without anti‐GROα and anti–MCP‐1 antibodies. Binding of β1 integrin receptors was assessed using integrin binding assays. Cytoskeletal assembly/disassembly in RASFs and HDECs were assessed by immunofluorescence staining for F‐actin. IL‐17A–induced cell migration and cytoskeletal disassembly were assessed in the presence of a Rac1 inhibitor (NSC23766). Rac1 activation following IL‐17 stimulation in the presence or absence of anti‐GROα, anti–MCP‐1, or IgG control was assessed by Rac GTPase pull‐down assays and Western blotting.

IL‐17A significantly up‐regulated angiogenesis and endothelial cell invasion. It significantly induced GROα and MCP‐1 expression in RASFs. Migration of PBMCs, RASFs, and HDECs was induced by IL‐17A; these effects were blocked by anti‐GROα or anti–MCP‐1 antibodies. IL‐17A significantly up‐regulated β1 integrin receptor binding and induced cytoskeletal disassembly in RASFs and HDECs. Rac1 activation was directly induced by IL‐17A. IL‐17A–induced wound repair and actin rearrangement were inhibited by a pharmacologic inhibitor of Rac1 (NSC23766). Anti‐GROα or anti–MCP‐1 antibodies had no effect on IL‐17A–induced Rac1 activation.

IL‐17A induces angiogenesis, cell migration, and cell invasion, all of which are key processes in the pathogenesis of rheumatoid arthritis and ones that are mediated in part through chemokine‐ and cytoskeleton‐dependent pathways.