Increased mesangial cell hyaluronan expression in lupus nephritis is mediated by anti-DNA antibody-induced IL-1β

The mechanism by which anti-DNA antibodies contribute to the pathogenesis of lupus nephritis (LN) remains to be fully elucidated. Hyaluronan (HA) is an important extracellular matrix constituent that accumulates during tissue injury, and participates in lymphocyte recruitment to sites of inflammation. The role of HA in the pathogenesis of LN has not been defined. We investigated the expression of HA in renal biopsies and circulating HA levels in patients with diffuse proliferative LN, and the effect of human anti-DNA antibodies on HA synthesis in cultured human mesangial cells (HMC). HA expression was increased in the mesangium, and in the periglomerular and tubular distribution in LN kidney biopsies. LN patients showed increased levels of circulating HA, especially during active disease, which correlated with anti-DNA antibody titers (r=0.35, P=0.0234). Anti-DNA antibodies isolated during active LN but not remission increased de novo synthesis of 3H-labeled HA, which was accompanied by induction of HA synthase (HAS) II transcription, and enhanced IL-1β, IL-6, and tumor necrosis factor-α secretion in HMC (P