Targeting leukocyte MMPs and transmigration: minocycline as a potential therapy for multiple sclerosis.

Multiple sclerosis is characterized by the infiltration of leukocytes into the CNS. As matrix metalloproteinases (MMPs) facilitate the passage of leukocytes across matrix barriers, we tested the hypothesis that targeting MMPs could attenuate neuro-inflammation. We report that minocycline, a widely used generic drug with a good safety record, inhibited MMP activity, reduced production of MMP-9 and decreased the transmigration of T lymphocytes across a fibronectin matrix barrier.

Diminished levels of T cell receptor zeta chains in peripheral blood T lymphocytes from patients with systemic lupus erythematosus.

Objective: To examine the expression of molecules known to participate in early T cell receptor (TCR)/CD3 signaling in peripheral blood (PB) T lymphocytes from patients with systemic lupus erythematosus (SLE).

Methods: Signaling molecules were analyzed by immunoprecipitation and Western blotting of unstimulated PB T lymphocyte cell lysates from SLE patients, non-SLE disease controls, and healthy controls. Flow cytometry was used for analysis of the expression of membrane markers in intact cells.

Protein tyrosine kinase activity in T lymphocytes from patients with systemic lupus erythematosus.

We have recently observed an abnormal pattern of protein tyrosine phosphoryl-ation in resting T lymphocytes obtained from peripheral blood of patients with systemic lupus erythematosus (SLE). To examine whether these findings may be related to dysregulated protein tyrosine kinase (PTK) function, we tested the relative amount and enzyme activity of the main PTKs involved in the earliest signalling steps triggered via the CD3 pathway. Cell lysates from peripheral blood T cells in SLE patients showed lower amounts of p59(fyn) and p56(lck) as shown by immunoblot.