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W L Matzner

Publications and source records attributed to W L Matzner.

4 recordsLinked to original sources
PubMed1991

Inhibition of protein-kinase C in peripheral blood mononuclear cells of patients with systemic lupus erythematosus: effect on spontaneous immunoglobulin production.

Systemic Lupus Erythematosus (SLE) is a multisystem disease characterized by an increase in the spontaneous secretion of immunoglobulin (Ig) molecules, many of which are autoreactive. We have previously shown (Biochem & Biophys. Res. Comm. (1989) 161: 1319-1326) that normal human peripheral blood mononuclear cells (PBMCs) can be stimulated to secrete large quantities of Ig upon incubation with the protein kinase-C activator 1 oleoyl-2-acetyglycerol (OAG). Specific blockage of protein kinase C with the isoquinoline sulfonyl piperazine compound (H-7) inhibited the OAG-induced Ig production. In experiments reported here, PBMC of 5 patients with active SLE produced high levels of IgG spontaneously in culture. PBMC of 6 inactive SLE patients and 7 normal control subjects produced comparable low levels of IgG spontaneously. Pokeweed mitogen (PWM) stimulation of PBMC in inactive SLE and control groups, but not active SLE patients produced markedly enhanced IgG production. The lack of response to PWM stimulation in active SLE patients is likely due to inherent maximal stimulation of active SLE B-cells. In addition, we examined the ability of H-7 to inhibit both mitogen-stimulated (normal and inactive SLE) and spontaneous (active SLE) Ig production. In other experiments, we also examined the ability of the isoquinoline sulfonamide (HA-1004), a potent inhibitor of cAMP-dependent protein kinase to regulate mitogen stimulated and spontaneous Ig production in the patient groups indicated above. H-7 significantly inhibited PWM stimulated Ig production in normal (P less than 0.0001) and inactive SLE patients, (P less than 0.040) suppressing PWM stimulated levels to spontaneous levels.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

1,25 dihydroxyvitamin-D3 regulation of immunoglobulin production in peripheral blood mononuclear cells of patients with systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) is a multisystem disease characterized by an increase in the secretion of autoantibodies. The mechanisms of autoantibody-induced disease have not been clarified. 1,25-Dihydroxy-vitamin D3 (1,25-D3) is known to be important in the regulation of normal human lymphocyte functions. Among its regulatory functions is the ability to inhibit mitogen-stimulated production of immunoglobulin. The experiments reported here explored the regulation of IgG production by peripheral blood mononuclear cells (PBMCs) of patients with inactive and active SLE. 1,25-Dihydroxyvitamin D3 inhibited mitogen-stimulated IgG production in cells from normal individuals and inactive SLE patients, but not spontaneous IgG production by PBMCs from active SLE patients. Addition of exogenous IL-2 (5-50 U/ml) to 1,25-D3-treated cells from all patient groups did not affect IgG production significantly under any conditions tested. The addition of IL-2 to PMBCs had no effect on IgG production in normal individuals or inactive SLE patients, but stimulated IgG production in PBMCs of active SLE patients. We conclude that the regulation of mitogen-stimulated IgG production in inactive SLE patients by 1,25-D3 and IL-2 is similar to normal individuals, but IgG production by active SLE PBMCs is unresponsive to 1,25-D3 regulation and is increased with the addition of IL-2.

Adult↗