Premium
The Anti‐Inflammatory Cytokine Interleukin‐19 Inhibits Smooth Muscle Cell Migration and Activation of Cytoskeletal Regulators of VSMC Motility
Author(s) -
Gabunia Khatuna,
Jain Surbhi,
England Ross,
Autieri Michael
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.616.9
Vascular Smooth Muscle Cell (VSMC) migration is an important cellular event in multiple vascular diseases. We tested the hypothesis that an anti‐inflammatory, Th2 interleukin, Interleukin‐19 (IL‐19) could decrease VSMC motility. IL‐19 significantly decreased PDGF‐stimulated VSMC chemotaxis in Boyden chambers and migration in scratch wound assays. IL‐19 significantly decreased VSMC spreading in response to PDGF. To determine the molecular mechanism(s), we examined the effect of IL‐19 on activation of proteins which regulate VSMC cytoskeletal dynamics and locomotion. IL‐19 decreased PDGF‐driven activation of several regulatory proteins which play an important role in SMC motility, including heat shock protein‐27 (HSP27), myosin light chain (MLC), and cofilin. IL‐19 decreased PDGF activation of the Rac1 and RhoA GTPases, important integrators of migratory signals. IL‐19 was unable to inhibit VSMC migration, nor was able to inhibit activation of cytoskeletal regulatory proteins in VSMC transduced with a constitutively active Rac1 mutant (RacV14), suggesting that IL‐19 inhibits events proximal to Rac1 activation. Together, these data are the first to indicate that IL‐19 can have important inhibitory effects on VSMC motility and activation of cytoskeletal regulatory proteins. This has important implications for the use of anti‐inflammatory cytokines in the treatment of vascular occlusive disease.