LPS-evoked IL-18 expression in mesangial cells plays a role in accelerating lupus nephritis

H. A. Shui, S. M. Ka, W. M. Wu, Y. F. Lin, Y. C. Hou, L. C. Su, A. Chen

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Objectives. Systemic lupus erythematosus is occasionally accompanied with bacterial infection. Lipopolysaccharide (LPS) from bacteria can accelerate and exacerbate lupus nephritis (LN) in animal models, but some mechanisms underlying the LPS-induced acceleration are still unclear. First, it is not known whether LPS can stimulate mesangial cells (MCs) to secrete the pro-inflammatory cytokine, interleukin (IL)-18. Second, it is also unclear whether LPS and/or IL-18 can induce MC apoptosis. Here, we attempted to clarify the cause-and-effect relationships between LPS stimulation, IL-18 production and MC apoptosis to address the above questions. Methods. LPS was used to induce accelerated LN in LN-prone mice. LPS and IL-18 were also used to treat cultured MCs isolated from the mice. IL-18 expression and MC apoptosis were investigated by in situ hybridization, the TUNEL method, reverse transcription- polymerase chain reaction (RT-PCR), western blotting, DNA electrophoresis and flow cytometry. NFκB was detected by immunofluorescent staining. Results. In the LPS-accelerated LN mice, we observed co-existence of IL-18 expression, hyperplasia, apoptosis, and activated apoptotic signal transduction in MCs, as well as marked neutrophil infiltration in the glomerulus, especially around the mesangial region. In cultured MCs, LPS greatly enhanced IL-18 expression, but did not induce apoptosis, while mouse IL-18 did not induce apoptosis or activate apoptotic signal transduction in MCs. Conclusions. We conclude that LPS can evoke IL-18 production in MCs, but neither LPS nor IL-18 directly induces apoptosis or activates apoptotic signal transduction in the cells. We infer that LPS-induced IL-18 production by MCs could be a mediator by which LPS accelerates and exacerbates LN.

Original languageEnglish
Pages (from-to)1277-1284
Number of pages8
JournalRheumatology
Volume46
Issue number8
DOIs
Publication statusPublished - Aug 2007
Externally publishedYes

Keywords

  • Accelerated LN
  • Apoptosis
  • IL-18
  • LPS
  • Lupus nephritis
  • Mesangial cells

ASJC Scopus subject areas

  • Neuroscience(all)
  • Rheumatology

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