Chronic shift-lag alters the circadian clock of NK cells and promotes lung cancer growth in rats.
Chronic shift-lag alters the circadian clock of NK cells and promotes lung cancer growth in rats.
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DOI：
10.4049/jimmunol.1102715
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发表时间：
2012-03-15
期刊：
影响因子：
--
通讯作者：
Sarkar DK
中科院分区：
文献类型：
--
作者：
Logan RW;Zhang C;Murugan S;O'Connell S;Levitt D;Rosenwasser AM;Sarkar DK
长期从事不稳定的工作或照明时间表，特别是轮班工作者，与免疫相关疾病的风险增加有关，包括几种癌症。慢性昼夜节律破坏的后果也可能延伸到先天免疫系统，以促进癌症生长，因为自然杀伤（NK）细胞功能受昼夜节律机制调节，并在肿瘤细胞裂解中起关键作用。为了确定NK细胞功能是否被人类轮班工作和时差模型破坏，Fischer（344）大鼠暴露于标准12：12光-暗循环或慢性轮班-时差模式，所述模式由每2天发生的10次重复的6小时光推进组成，随后是5-7天的恒定黑暗。这种模式导致了相当大的昼夜节律的破坏，评估昼夜运行轮活动。从对照和转换动物中富集NK细胞，并进行基因、蛋白质和细胞溶解活性测定。慢性移位滞后改变了时钟基因Per 2和Bmal 1、细胞溶解因子穿孔素和颗粒酶B以及细胞因子IFNγ的昼夜表达。这些变化与抑制NK细胞溶解活性的昼夜表达相关。此外，在静脉内注射MADB 106肿瘤细胞后，在刺激的体内条件下，慢性移位滞后减弱NK细胞的细胞溶解活性，并促进肺肿瘤生长。总之，这些发现表明慢性昼夜节律破坏通过改变NK细胞功能的昼夜节律促进肿瘤生长。
Prolonged subjection to unstable work or lighting schedules, particularly in rotating shift-workers, is associated with an increase risk of immune-related diseases, including several cancers. Consequences of chronic circadian disruption may also extend to the innate immune system to promote cancer growth, as natural-killer (NK) cell function is modulated by circadian mechanisms and plays a key role in lysis of tumor cells. In order to determine if NK cell function is disrupted by a model of human shift-work and jet-lag, Fischer (344) rats were exposed to either a standard 12:12 light-dark cycle, or a chronic shift-lag paradigm, consisting of ten repeated 6 hour photic advances occurring every 2 days, followed by 5–7 days of constant darkness. This model resulted in considerable circadian disruption as assessed by circadian running wheel activity. NK cells were enriched from control and shifted animals, and gene, protein, and cytolytic activity assays were performed. Chronic shift-lag altered the circadian expression of clock genes, Per2 and Bmal1, and cytolytic factors, perforin and granzyme B, as well as the cytokine, IFNγ. These alterations were correlated with suppressed circadian expression of NK cytolytic activity. Further, chronic shift-lag attenuated NK cell cytolytic activity under stimulated in-vivo conditions, and promoted lung tumor growth, following intravenous injection of MADB106 tumor cells. Together, these findings suggest chronic circadian disruption promotes tumor growth by altering the circadian rhythms of NK cell function.
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DOI：
10.4049/jimmunol.1001026
发表时间：
2010-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Castanon-Cervantes O;Wu M;Ehlen JC;Paul K;Gamble KL;Johnson RL;Besing RC;Menaker M;Gewirtz AT;Davidson AJ
通讯作者：
Davidson AJ
影响因子：
3.7
作者：
Gibson EM;Wang C;Tjho S;Khattar N;Kriegsfeld LJ
通讯作者：
Kriegsfeld LJ
影响因子：
4.9
作者：
Chaput, J-P;Brunet, M.;Tremblay, A.
通讯作者：
Tremblay, A.
影响因子：
2.3
作者：
Arjona, Alvaro;Sarkar, Dipak K.
通讯作者：
Sarkar, Dipak K.
影响因子：
15.1
作者：
Arjona, Alvaro;Sarkar, Dipak K.
通讯作者：
Sarkar, Dipak K.