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The underlying mechanism causing acceleration and exacerbation of lupus nephritis (LN) is largely unknown. Bacterial lipopolysaccharide (LPS) is capable of inducing an accelerated model of LN in NZB\/W mice, featuring diffuse proliferation of glomerular resident cells. We hypothesized that mesangial cells (MCs) from LN subjects are more responsive to LPS than normal subjects. Cultured primary NZB\/W and DBA\/W (nonautoimmune disease-prone strain with MHC class II molecules identical to those of NZB\/W) MCs were used. Monocyte chemoattractant protein-1 (MCP-1) and osteopontin (OPN) expressions either in the baseline (normal culture) condition or in the presence of LPS were evaluated by real-time PCR, ELISA, or western blot analysis. NF-\u03baB was detected by ELISA, electrophoresis mobility-shift assay, and immunofluorescence. First, either in the baseline condition or in the presence of LPS, NZB\/W MCs produced significantly higher levels of MCP-1 and OPN than the DBA\/W MC controls. Second, NZB\/W MCs expressed significantly higher levels of Toll-like receptor 4, myeloid differentiation factor 88, and NF-\u03baB than the DBA\/W MC controls, both receiving exactly the same LPS treatment. In conclusion, NZB\/W MCs are significantly more sensitive than their normal control DBA\/W MCs in producing both MCP-1 and OPN. With LPS treatment, the significantly elevated levels of both chemokines produced by NZB\/W MCs are more likely due to a significantly greater activation of the Toll-like receptor 4-myeloid differentiation factor 88-associated NF-\u03baB pathway. The observed abnormal molecular events provide an intrarenal pathogenic pathway involved in an accelerated type of LN, which is potentially infection triggered.<\/jats:p>","DOI":"10.1186\/ar2226","type":"journal-article","created":{"date-parts":[[2007,7,7]],"date-time":"2007-07-07T06:23:04Z","timestamp":1183789384000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Mesangial cells of lupus-prone mice are sensitive to chemokine production"],"prefix":"10.1186","volume":"9","author":[{"given":"Shuk-Man","family":"Ka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Wen","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Ai","family":"Shui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Mein","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deh-Ming","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2007,7,7]]},"reference":[{"key":"2077_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1191\/0961203305lu2054oa","volume":"14","author":"M Waldman","year":"2005","unstructured":"Waldman M, Madaio MP: Pathogenic autoantibodies in lupus nephritis. 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