Blood vitronectin is a major activator of LIF and IL-6 in the brain through integrin-FAK and uPAR signaling.

ABSTRACT: We defined how blood-derived vitronectin (VTN) rapidly and potently activates leukemia inhibitory factor (LIF) and pro-inflammatory interleukin 6 (IL-6) in vitro and after vascular injury in the brain. Treatment with VTN (but not fibrinogen, fibronectin, laminin-111 or collagen-I) substantially increased LIF and IL-6 within 4 h in C6-astroglioma cells, while VTN-/- mouse plasma was less effective than that from wild-type mice. LIF and IL-6 were induced by intracerebral injection of recombinant human (rh)VTN in mice, but induction seen upon intracerebral hemorrhage was less in VTN-/- mice than in wild-type littermates. In vitro, VTN effects were inhibited by RGD, αvβ3 and αvβ5 integrin-blocking peptides and antibodies. VTN activated focal adhesion kinase (FAK; also known as PTK2), whereas p

SUBMITTER: Keasey MP 

PROVIDER: S-EPMC5826040 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature