title: Type III interferon induces apoptosis in human lung cancer cells.
abstract: The apoptotic effects of interferon lambdas (IFNλs) have been described             in several types of cancers. However, their effects on human lung cancer cells             and the mechanisms are elusive. In addition, the interaction between IFNλs and             other interferons remains unclear. The interplay between IFNα and IFNλ has been             reported. However, although IFNγ is a well-known regulatory interferon, the mechanisms             through which it regulates IFNλs in lung cancer cells are unknown. These issues             are critical for the application of IFNλs in lung cancer therapy. In this study,             we used A549, a cell line derived from a human lung carcinoma, to characterize             the antiproliferative and apoptotic effects of IFNλs on lung cancer, and the interplay             between IFNγ and IFNλ. Because overexpression of full-length ectopic IFNλR1 led             to cell death, we generated A549 cells stably expressing a chimeric receptor (10R1/λR1),             which is composed of the extracellular domain of IL-10 receptor (IL10R1) fused             in tandem to the transmembrane and intracellular domains of the IFNλ receptor             (IFNλR1). By comparing with A549 cells stably expressing its cognate vector, we             demonstrated that IL-10 stimulation triggered the intracellular IFNλ signaling             via 10R1/λR1 receptor. By using A549 cells expressing 10R1/λR1, we report that             the IFNλR1 chain of IFNλ receptor possesses an intrinsic ability to trigger apoptosis             in human lung cancer cells. Although it did not suppress cell proliferation, IFNλ             signaling via 10R1/λR1 receptor induced cell cycle arrest, externalization of             phosphatidylserine, DNA fragmentation, activation of caspase-3, caspase-8 and             caspase-9. However, the caspase inhibitor Z-VAD-FMK did not prevent apoptosis.             In addition, the extent of induced apoptosis correlate with the expression levels             of the IFNλ receptor and the levels of STAT1 activation. Lastly, we demonstrated             that IFNγ sensitized A549 cells to IFNλ-induced apoptosis, via upregulation of             IFNλR1. These data indicate the potential of IFNλ, alone or in combination with             IFNγ, in the treatment of human lung carcinoma.
authors: Department of Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing 100069, PR China.
authors: Wei
authors: W
authors: Li
authors: Xiaojie
authors: X
authors: Huang
authors: Zhuoming
authors: Z
authors: Liu
authors: Yuxuan
authors: Y
authors: Wang
authors: Hongwei
authors: H
authors: Zhang
authors: Hongfei
authors: H
authors: Tong
authors: Hao
authors: H
authors: Wu
authors: Shengzhang
authors: S
authors: Lin
mesh_terms: D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D053938:DNA Fragmentation; D004789:Enzyme Activation; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology; D007372:Interferons; D016753:Interleukin-10 / Q000494:pharmacology / Q000502:physiology; D053709:Interleukin-10 Receptor alpha Subunit / Q000378:metabolism; D007378:Interleukins / Q000494:pharmacology / Q000502:physiology*; D008175:Lung Neoplasms; D017471:Receptors, Interferon / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000095022:Interferon Lambda
chemical_list: D020169:Caspases; D007371:Interferon-gamma; D007372:Interferons; D016753:Interleukin-10; D053709:Interleukin-10 Receptor alpha Subunit; D007378:Interleukins; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C508609:IL10 protein, human; C494079:STAT1 protein, human