Cytokine effects on cell survival and death of A549 lung carcinoma cells

Purpose: IL-13, TNF-alpha and IL-1 beta have various effects on lung cancer growth and death, but the signaling pathways mediating these effects have not been extensively analyzed. Therefore, the effects of IL-13, TNF-alpha and IL-1 beta alone, and in combination with Fas, on cell viability and death as well as major signaling pathways involved in these effects were investigated in A549 lung carcinoma cells. Results: Using MU and flow cytometry, IL-13, TNF-alpha and IL-1 beta pretreatment decreased Fas-induced cell death. These anti-cell death effects were attenuated by pretreatment with inhibitors of Nuclear factor-kappa B [NF-kappa B], Phoshatidylinositole-3 kinase [PI3-K], JNK, p38 and ERK1/2 pathways. Results: Using Western blot, IL-13, TNF-alpha and IL-1 beta treated cells showed time-dependent expression of p-ERK1/2, p-p38, p-JNK, p-Akt and p-I kappa B alpha proteins, decreased I kappa B alpha protein expression, no cleavage of Caspase-3 and PARP1 proteins and no notable alterations of Fas protein. IL-13 and TNF-alpha treated cells showed time-dependent increase of FLIPL expression. Conclusion: IL-13, TNF-alpha and IL-1 beta attenuate the pro-cell death effects of Fas on A549 cells, at least partially, by pathways involving the NF-kappa B, PI3-K and MAP kinases, but not by alterations of Fas protein expression. The IL-13 and TNF-alpha cell survival effects may also be due to increased expression of FLIPL protein. (C) 2013 Elsevier Ltd. All rights reserved.