Circadian oscillations of clock genes, cytolytic factors, and cytokines in rat NK cells.
A growing body of knowledge is revealing the critical role of circadian physiology in the development of specific pathological entities such as cancer. NK cell function participates in the immune response against infection and malignancy. We have reported previously the existence of a physiological circadian rhythm of NK cell cytolytic activity in rats, suggesting the existence of circadian mechanisms subjacent to NK cell function. At the cellular level, circadian rhythms are originated by the sustained transcriptional-translational oscillation of clock genes that form the cellular clock apparatus. Our aim in this study was to investigate the presence of molecular clock mechanisms in NK cells as well as the circadian expression of critical factors involved in NK cell function. For that purpose, we measured the circadian changes in the expression of clock genes (Per1, Per2, Bmal1, Clock), Dbp (a clock-controlled output gene), CREB (involved in clock signaling), cytolytic factors (granzyme B and perforin), and cytokines (IFN-gamma and TNF-alpha) in NK cells enriched from the rat spleen. The results obtained from this study demonstrate for the first time the existence of functional molecular clock mechanisms in NK cells. Moreover, the circadian expression of cytolytic factors and cytokines in NK cells reported in this study emphasizes the circadian nature of NK cell function.
Arjona
Alvaro
A
Endocrinology Program, Center of Alcohol Studies and Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
Sarkar
Dipak K
DK
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D002460:Cell Line; D002469:Cell Separation / Q000379:methods; D002940:Circadian Rhythm / Q000235:genetics / Q000276:immunology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D053804:Granzymes; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D054353:Perforin; D010766:Phosphorylation; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D053804:Granzymes; D007371:Interferon-gamma; D008562:Membrane Glycoproteins; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D015534:Trans-Activators; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C538945:Clock protein, rat; C509215:Gzmb protein, rat