Abstract
Systemic lupus erythematosus (SLE) is characterized by inflammatory and dysregulatory immune responses including overactive B cells, overproduction of proinflammatory cytokines, and T cell hyperactivity. PGE2 modulates a variety of immune processes at sites of inflammation, including production of inflammatory cytokines. However, the role of PGE2 in dysregulatory inflammatory and immune responses in lupus remains unclear. We investigated whether PGE2 mediates production of inflammatory cytokines in pristane-induced lupus BALB/c mice. Our results showed that levels of serum and BAL PGE2 and LPS-stimulated production of PGE2 by peritoneal macrophages were remarkably increased in pristane-induced lupus mice compared to healthy controls. Exogenous PGE2 enhanced production of IL-6, IL-10, and NO but decreased TNF-α by macrophages and augmented IFN-γ, IL-6, and IL-10 by splenocytes from pristane-induced lupus mice compared to healthy controls. Exogenous PGE2 also enhanced production of IFN-γ, IL-6, and IL-10 by thymocytes from pristane-induced lupus mice. Indomethacin (Indo), a PGE2 synthesis inhibitor, greatly inhibited LPS-induced production of IL-6 and IL-10 by macrophages from pristane-induced lupus mice, while enhanced TNF-α. Indo remarkably inhibited Con A-increased production of IFN-γ, IL-6, and IL-10 by splenocytes and thymocytes from pristane-induced lupus mice. Therefore, our findings suggest that endogenous PGE2 may mediate dysregulation of production of proinflammatory cytokines, such as IL-6, IL-10, and IFN-γ, and NO in pristane-induced lupus mice.
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Chae, B.S., Shin, T.Y., Kim, D.K. et al. Prostaglandin E2-mediated dysregulation of proinflammatory cytokine production in pristane-induced lupus mice. Arch. Pharm. Res. 31, 503–510 (2008). https://doi.org/10.1007/s12272-001-1185-6
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DOI: https://doi.org/10.1007/s12272-001-1185-6