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 language | English |
|---|---|
| Pages (from-to) | 1277-1284 |
| Number of pages | 8 |
| Journal | Rheumatology |
| Volume | 46 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2007 |
| Externally published | Yes |
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Keywords
- Accelerated LN
- Apoptosis
- IL-18
- LPS
- Lupus nephritis
- Mesangial cells
ASJC Scopus subject areas
- Neuroscience(all)
- Rheumatology
Cite this
LPS-evoked IL-18 expression in mesangial cells plays a role in accelerating lupus nephritis. / Shui, H. A.; Ka, S. M.; Wu, W. M.; Lin, Y. F.; Hou, Y. C.; Su, L. C.; Chen, A.
In: Rheumatology, Vol. 46, No. 8, 08.2007, p. 1277-1284.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - LPS-evoked IL-18 expression in mesangial cells plays a role in accelerating lupus nephritis
AU - Shui, H. A.
AU - Ka, S. M.
AU - Wu, W. M.
AU - Lin, Y. F.
AU - Hou, Y. C.
AU - Su, L. C.
AU - Chen, A.
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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.
KW - Accelerated LN
KW - Apoptosis
KW - IL-18
KW - LPS
KW - Lupus nephritis
KW - Mesangial cells
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U2 - 10.1093/rheumatology/kem136
DO - 10.1093/rheumatology/kem136
M3 - Article
VL - 46
SP - 1277
EP - 1284
JO - Rheumatology
JF - Rheumatology
SN - 1462-0324
IS - 8
ER -