title: A Potential Role for PGE and IL-14 (HMW-BCGF) in B-Cell Hyperactivity of Patients with Systemic Lupus Erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a disease characterized by the prolonged production of high-affinity autoantibodies resulting in direct and immune complex-mediated tissue damage. Because autoantibody responses occur over several years, memory B cells are likely to be involved. Interleukin-14 (IL-14) is a cytokine implicated in the generation and maintenance of normal memory B cells. Many of the actions of IL-14, including inhibition of antibody synthesis and upregulation of IL-14 receptors (IL-14R), are dependent on the formation of prostaglandin E (PGE) and subsequently cAMP. We observed that IL-14 induces phospholipase A(2) (PLA(2))-dependent release of arachidonic acid from phosphatidylcholine and phosphatidylinositol. Production of PGE is blocked by the PLA(2) inhibitor bromophenacyl bromide. Exogenous PGE (misoprostol) induces similar inhibition of antibody synthesis and increases in IL-14R as IL-14. Lymphocytes from patients with inactive SLE were noted to spontaneously produce PGE. Lymphocytes from normal donors produced PGE only after Sac-activation and IL-14 stimulation. Peripheral B and T lymphocytes from SLE patients, but not normal donors, spontaneously produced IL-14. Increased numbers of peripheral B lymphocytes from patients with inactive SLE expressed IL-14R, when compared to normal donors. Thus, increased production of IL-14 and PGE in SLE may result in expansion of a memory B-cell population capable of long-term autoantibody production. Further study will be necessary to confirm these preliminary findings and to examine in greater depth the regulation of PGE and IL-14 in SLE patients and normal donors.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, USA.
authors.forename: Julian L.
authors.initials: JL
authors.lastname: Ambrus
authors.forename: Varsha
authors.initials: V
authors.lastname: Contractor
authors.forename: Amy
authors.initials: A
authors.lastname: Joseph
authors.forename: John
authors.initials: J
authors.lastname: Long
authors.forename: David
authors.initials: D
authors.lastname: Blumenthal