Chronic sleep deprivation disrupts the circadian clock and increases susceptibility to diseases such as diabetes, obesity, and cancer. Increased inflammation is one of the common underlying mechanisms of these diseases in addition to being a factor in mood disorders such as depression. The authors of this study investigated whether circadian clock proteins may regulate immune response. They found that the absence of the core clock component protein cryptochrome (CRY) leads to constitutive elevation of proinflammatory cytokines in a cell-autonomous manner. In terms of specific pathways affected, the authors propose that the absence of CRY protein(s) might release inhibition on cyclic AMP production, resulting in elevated cyclic AMP and increased protein kinase A enzyme activation, subsequently leading to NF–κB activation through phosphorylation of p65 at S276. This results in the production of proinflammatory cytokines. These results offer a possible mechanism for understanding the link between circadian rhythm disruption and increased susceptibility to chronic inflammatory diseases.
Narasimamurthy R, Hatori M, Nayak SK , Liu F, Panda S, and Verma IM: Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines. Proc. Natl. Acad. Sci. USA [Epub ahead of print, July 9, 2012; doi: 10.1073/pnas.1209965109]