Marwick John A, Kirkham Paul, Gilmour Peter S, Donaldson Kenneth, MacNEE William, Rahman Irfan
Respiratory Medicine Unit, ELEGI and Colt Laboratory, University of Edinburgh, Medical School, Edinburgh, UK.
Ann N Y Acad Sci. 2002 Nov;973:278-83. doi: 10.1111/j.1749-6632.2002.tb04649.x.
Sustained oxidative stress caused by cigarette smoking induces a chronic inflammatory response, resulting in the destruction of the alveolar cell wall characteristic of emphysema. The loss of tissue may involve the progressive depletion of epithelial cells through inhibition of proliferation leading to cell death. The cell cycle regulator p21(waf1/cip1) acts as a G(1)/S and G(2)/M phase checkpoint regulator. We hypothesize that cigarette smoke-induced oxidative stress and transforming growth factor beta 1 (TGF-beta(1)) may inhibit cellular proliferation by p21(waf1/cip1) in type II alveolar epithelial cells (A549). A significant increase was observed in p21(waf1/cip1) mRNA expression in A549 cells by cigarette smoke condensate, H(2)O(2), and TGF-beta(1). In conclusion, cigarette smoke-induced oxidative stress and TGF-beta(1) modulate expression of the cell cycle inhibitor p21(waf1/cip1). This may be important in the growth arrest and cell survival of alveolar type II cells in the G(1) phase.
吸烟引起的持续氧化应激会引发慢性炎症反应,导致肺气肿特有的肺泡细胞壁破坏。组织的丧失可能涉及上皮细胞通过抑制增殖导致细胞死亡而逐渐耗竭。细胞周期调节因子p21(waf1/cip1)作为G(1)/S和G(2)/M期检查点调节因子。我们假设香烟烟雾诱导的氧化应激和转化生长因子β1(TGF-β(1))可能通过p21(waf1/cip1)抑制II型肺泡上皮细胞(A549)的细胞增殖。香烟烟雾冷凝物、H(2)O(2)和TGF-β(1)使A549细胞中p21(waf1/cip1)mRNA表达显著增加。总之,香烟烟雾诱导的氧化应激和TGF-β(1)调节细胞周期抑制剂p21(waf1/cip1)的表达。这可能对II型肺泡细胞在G(1)期的生长停滞和细胞存活很重要。