Rheumatology Advance Access originally published online on June 14, 2007
Rheumatology 2007 46(8):1277-1284; doi:10.1093/rheumatology/kem136
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LPS-evoked IL-18 expression in mesangial cells plays a role in accelerating lupus nephritis
1Graduate Institute of Medical Sciences, 2Department of Pathology and 3Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center and 4Department of Nutrition and Food Sciences, Fu-Jen University, Taipei, Taiwan, R.O.C.
Correspondence to: A. Chen, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Gung Road, Taipei, Taiwan, ROC. E-mail: doc31717{at}ndmctsgh.edu.tw
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Abstract |
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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. NF
B 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.
KEY WORDS: LPS, IL-18, Lupus nephritis, Mesangial cells, Apoptosis, Accelerated LN
Submitted 3 January 2007;
revised version accepted 13 April 2007.
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