Hydroquinone and catechol interfere with T cell cycle entry and progression through the G1 phase.
Cigarette smoking causes profound suppression of pulmonary T cell responses, which is associated with increased susceptibility to respiratory tract infections and decreased tumor surveillance. Hydroquinone (HQ) and catechol, at concentrations comparable to those found in cigarette smoke, are potent inhibitors of T cell activation and proliferation. We have previously shown that HQ and catechol inhibit ribonucleotide reductase, the rate-limiting enzyme in DNA synthesis. In this report we demonstrate that HQ and catechol also inhibit blastogenesis by interfering with T cell cycle entry and progression through the G(1) phase. In an attempt to localize the point in the cell cycle where arrest occurred, a set of key markers of activation and cell cycle progression were examined, including induction of c-Myc, up regulation of RNA synthesis, surface expression of CD71, and induction of E2F-dependent gene expression. Addition of HQ or catechol prior to stimulation inhibited each of these events without decreasing cell viability. However, production of IL-2 and surface expression of CD69 and CD25 were not affected, indicating that HQ and catechol inhibit only certain cell cycle events. These studies provide further indication of the regulatory pathways by which cigarette smoke inhibits T cell responses in the lungs of smokers.
Division of Allergy and Clinical Immunology, University of Colorado Health Sciences Center, 4200 E. 9th Ave, B-164, Denver, CO 80262, USA.
Jesica M
JM
McCue
Sabine
S
Lazis
J
J
John Cohen
Jaime F
JF
Modiano
Brian M
BM
Freed
D015703:Antigens, CD / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology*; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011990:Receptors, Transferrin; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D000099192:CD69 Antigens
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D002396:Catechols; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D006873:Hydroquinones; D007376:Interleukin-2; D037181:Lectins, C-Type; D016271:Proto-Oncogene Proteins c-myc; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D014157:Transcription Factors; D000099192:CD69 Antigens; C068126:CD71 antigen; C034221:catechol; C031927:hydroquinone