EFFECT OF NICOTINE ON SECRETORY COMPONENT SYNTHESIS BY SECRETORY EPITHELIAL-CELLS

Previously, we reported that secretory component (SC), lactoferrin (LF ), and lysozyme (LY) levels were significantly lower in saliva from sm okeless tobacco (ST) users than in saliva from control non-tobacco use rs. However, the levels of salivary immunoglobulin A were significantl y higher, albeit with an altered attachment of SG, in ST users than in control subjects. SC, LF, and LY are synthesized by secretory epithel ial cells at mucosal sites adjacent to lymphocyte regions. In the pres ent report, HTF-29 human epithelial cells, cultured with various conce ntrations of an ST aqueous extract or pure nicotine (0 to 1 mg/ml) or cotinine (0 to 5 mg/ml), exhibited significantly lower Levels of cell- associated cell lysate (CE) and secreted culture supernatant (CS) SC, LF, and LY than cells cultured without ST components. Nicotine signifi cantly decreased (P less than or equal to 0.05) the synthesis of SC by 20 to 100%, LF by 20 to 60%, and LY by 5 to 75% of CE and CS control values. Studies also indicated significant decreases (P less than or e qual to 0.05) ill SC, LF, and LY levels in both CL and CS of cells cul tured with ST aqueous extract or cotinine, Total cell numbers and meta bolic activity significantly decreased primarily when cells were incub ated with higher concentrations of ST extract, nicotine, or cotinine, The addition of human recombinant interleukin-4 or gamma interferon di minished the effects ST had on HT-29 cell synthesis of SC, LF, and LY. Our data indicate that nicotine, cotinine, and ST have an adverse eff ect on synthesis and secretion of Se, LF, and LY, These effects were b elow ST concentrations found to be cytotoxic for secretory epithelial cells. Furthermore, addition of interleukin-4 or gamma interferon redu ced the suppressive effect of ST on synthesis or secretion of SC, LF, or LY.