Suppression of tumor necrosis factor α-induced matrix metalloproteinase 9 production by the introduction of a super-repressor form of inhibitor of nuclear factor κBα complementary DNA into immortalized human salivary gland acinar cells: Prevention of the destruction of the acinar structure in Sjögren's syndrome salivary glands

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Abstract
Objective We have previously shown that specific enhancement in acinar cells of proteolytic activity induced by tumor necrosis factor α (TNFα) may be responsible for the destruction of the acinar structure in the salivary glands of patients with Sjögren's syndrome. Because matrix metalloproteinase 9 (MMP‐9) is regulated by nuclear factor κB (NF‐κB), we investigated the effect of a super‐repressor form of inhibitor of nuclear factor κBα (srIκBα) on the suppression of TNFα‐induced MMP‐9 production in acinar cells. Methods Two srIκBα complementary DNA (cDNA)–transfected acinar cell clones (ACMT‐6 and ACMT‐7) and 1 empty vector–transfected cell clone (ACpRc‐1) were established. After treatment of cell clones with TNFα, the expression of MMP‐9 was examined. In addition, the effect of TNFα on cell growth and the morphogenetic behavior of cell clones cultured on type IV collagen–coated dishes were examined. Results TNFα induced the production of MMP‐9 in the ACpRc‐1 cell clone, but greatly suppressed MMP‐9 production in ACMT‐6 and ACMT‐7 clones. No apparent cytotoxic effect of TNFα treatment was observed in these cell clones. When ACpRc‐1 cells were seeded on type IV collagen–coated dishes in the presence of both TNFα and plasmin, type IV collagen interaction with the cells was lost and the cells entered apoptosis. However, even when ACMT‐6 and ACMT‐7 cells were cultured under the same culture conditions as those for ACpRc‐1, these cell clones attached to the substrate and grew consistently without showing apoptosis. Conclusion These observations indicate that suppression of TNFα‐induced MMP‐9 production by the introduction of srIκBα cDNA corrected the aberrant in vitro morphogenesis of acinar cells grown on type IV collagen.