Fig. 5

A disintegrin and metalloprotease 17 (ADAM17) contributes to the shedding of semaphorin 7A (Sema7A). a Shedding of Sema7A is inhibited by metalloproteinase inhibitors. Western blots show Sema7A in the supernatant of THP-1 and CD14⁺ cells stimulated with tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the presence of the metalloprotease inhibitor GM6001 or the ADAM17-selective inhibitor BMS-561392 (BMS). Results shown are representative of three independent experiments. b Elevated serum ADAM17 levels in 26 patients with rheumatoid arthritis (RA) and 23 healthy donors. d Synovial fluid levels of ADAM17 in 11 patients with RA and 8 patients with osteoarthritis (OA). c Synovial fluid levels of ADAM17 in 11 patients with RA and 8 patients with osteoarthritis (OA).  d ADAM17 protein levels in primary cultures of TNF-α- and IL-6-stimulated synovial macrophages from patients with RA. Data were compiled from three independent experiments. Values are mean ± SEM. **P < 0.01. e HEK293T cells stably expressing transmembrane Sema7A (HEK293T_Sema7A) were transduced with vectors encoding an ADAM17-specific short-hairpin RNA (shADAM17) or a nonspecific short-hairpin RNA (shNS). Levels of secreted Sema7A in the cell culture supernatant were analyzed by Western blotting. Results shown are representative of three independent experiments