CCL2 mediates the circadian response to low dose endotoxin

Duhart, José M.; Brocardo, Lucila; Fedele, Malena Lis Mul; Guglielmotti, Angelo; Golombék, Diego A.

doi:10.1016/j.neuropharm.2016.05.005

Cited by 15 publications

(23 citation statements)

References 43 publications

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“…4f). Recently, direct interactions among the circadian clock and CCL2 have been reported to mediate time-of-day dependent responses to peripheral endotoxin administration, with peak hypothalamic CCL2 expression during the dark (inactive) phase33. Therefore, the phenotype we observed within the hypothalamus may be driven by time-of-day dependent recruitment of peripheral monocytes/macrophages into the brain.…”

Section: Discussionmentioning

confidence: 67%

Time-of-Day Dictates Transcriptional Inflammatory Responses to Cytotoxic Chemotherapy

Borniger

Walker

Gaudier-Diaz

et al. 2017

Sci Rep

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Many cytotoxic chemotherapeutics elicit a proinflammatory response which is often associated with chemotherapy-induced behavioral alterations. The immune system is under circadian influence; time-of-day may alter inflammatory responses to chemotherapeutics. We tested this hypothesis by administering cyclophosphamide and doxorubicin (Cyclo/Dox), a common treatment for breast cancer, to female BALB/c mice near the beginning of the light or dark phase. Mice were injected intravenously with Cyclo/Dox or the vehicle two hours after lights on (zeitgeber time (ZT2), or two hours after lights off (ZT14). Tissue was collected 1, 3, 9, and 24 hours later. Mice injected with Cyclo/Dox at ZT2 lost more body mass than mice injected at ZT14. Cyclo/Dox injected at ZT2 increased the expression of several pro-inflammatory genes within the spleen; this was not evident among mice treated at ZT14. Transcription of enzymes within the liver responsible for converting Cyclo/Dox into their toxic metabolites increased among mice injected at ZT2; furthermore, transcription of these enzymes correlated with splenic pro-inflammatory gene expression when treatment occurred at ZT2 but not ZT14. The pattern was reversed in the brain; pro-inflammatory gene expression increased among mice injected at ZT14. These data suggest that inflammatory responses to chemotherapy depend on time-of-day and are tissue specific.

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Section: Discussionmentioning

confidence: 67%

Time-of-Day Dictates Transcriptional Inflammatory Responses to Cytotoxic Chemotherapy

Borniger

Walker

Gaudier-Diaz

et al. 2017

Sci Rep

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“…A knockout of the TNF‐α receptor eliminates the LPS‐induced phase delay of locomotor activity as well as the change in expression of PER2 in the SCN (Paladino, Mul Fedele, Duhart, Marpegan, & Golombek, ). Similarly, a CCL2 inhibitor injection blunts LPS‐induced phase changes (Duhart et al, ). In summary, many cytokines and chemokines are secreted with a circadian rhythm, and the time of immune challenge or the absence of clock genes can greatly influence the magnitude of a cytokine response.…”

Section: Circadian Control Of Inflammatory Mediatorsmentioning

confidence: 99%

“…Chemokines such as CCL2 and CCL8 also have a circadian production when recruiting monocytes to sites of inflammation (Nguyen et al, ), while others (e.g., CCL3, CCL5, CXCL1, CXCL2, CX3CL1) were not found to have such effects (Scheiermann et al, ). CCL2 in particular has been observed in the SCN as being expressed higher during the active period (Duhart, Brocardo, Mul Fedele, Guglielmotti, & Golombek, ). Whether the time of day of activation alters the cytokine response remains debated.…”

Section: Circadian Control Of Inflammatory Mediatorsmentioning

confidence: 99%

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Circadian control of pain and neuroinflammation

Segal

Tresidder

Bhatt

et al. 2017

J of Neuroscience Research

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The importance of a neuroinflammatory response to the development and maintenance of inflammatory and neuropathic pain have been highlighted in recent years. Inflammatory cells contributing to this response include circulating immune cells such as monocytes, T and B lymphocytes, and neutrophils, as well as microglia in the central nervous system. Pain signals are transmitted via sensory neurons in the peripheral nervous system, which express various receptors and channels that respond to mediators secreted from these inflammatory cells. Chronobiological rhythms, which include the 24-hr circadian cycle, have recently been shown to regulate both nervous and immune cell activity and function. This review examines the current literature on chronobiological control of neuroinflammatory processes, with a focus on inflammatory and neuropathic pain states. While the majority of this work has stemmed from observational studies in humans, recent advances in using animal models have highlighted distinct mechanisms underlying these interactions. Better understanding interactions between the circadian and neuroimmune systems can help guide the development of new treatments and provide improved care for patients suffering from acute and chronic pain.

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“…Noteworthy, increased glutamate levels are characteristic in gliomas (reviewed in Robert and Sontheimer, 2014 ), suggesting that a dysregulation of proper glial function occurring in this malignant tissue may impact on both timekeeping and synchronization mechanisms of the clock. In addition, molecules involved in immune responses, such as TNF-α, IL-1β, and CCL2 have been shown to affect the master circadian oscillator (Nygård et al, 2009 ; Leone et al, 2012 ; Duhart et al, 2016 ). Gliomas drastically alter the microenvironment in which they develop, and molecules involved in the immune response have been shown to have an important role in tumor progression (Reviewed in Christofides et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Circadian Alterations in a Murine Model of Hypothalamic Glioma

et al. 2017

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The mammalian circadian system is controlled by a central oscillator located in the suprachiasmatic nuclei (SCN) of the hypothalamus, in which glia appears to play a prominent role. Gliomas originate from glial cells and are the primary brain tumors with the highest incidence and mortality. Optic pathway/hypothalamic gliomas account for 4–7% of all pediatric intracranial tumors. Given the anatomical location, which compromises both the circadian pacemaker and its photic input pathway, we decided to study whether the presence of gliomas in the hypothalamic region could alter circadian behavioral outputs. Athymic nude mice implanted with LN229 human glioma cells showed an increase in the endogenous period of the circadian clock, which was also less robust in terms of sustaining the free running period throughout 2 weeks of screening. We also found that implanted mice showed a slower resynchronization rate after an abrupt 6 h advance of the light-dark (LD) cycle, advanced phase angle, and a decreased direct effect of light in general activity (masking), indicating that hypothalamic tumors could also affect photic sensitivity of the circadian clock. Our work suggests that hypothalamic gliomas have a clear impact both on the endogenous pacemaking of the circadian system, as well as on the photic synchronization of the clock. These findings strongly suggest that the observation of altered circadian parameters in patients might be of relevance for glioma diagnosis.

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CCL2 mediates the circadian response to low dose endotoxin

Cited by 15 publications

References 43 publications

Time-of-Day Dictates Transcriptional Inflammatory Responses to Cytotoxic Chemotherapy

Time-of-Day Dictates Transcriptional Inflammatory Responses to Cytotoxic Chemotherapy

Circadian control of pain and neuroinflammation

Circadian Alterations in a Murine Model of Hypothalamic Glioma

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