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Cold-inducible RNA-binding protein is an important mediator of alcohol-induced brain inflammation.

Rajayer SR, Jacob A, Yang WL, Zhou M, Chaung W, Wang P - PLoS ONE (2013)

Bottom Line: At 5 h after alcohol, a significant increase of 53% in the brain of CIRP mRNA was observed and its expression remained elevated at 10 h and 15 h.From this we conclude that alcohol exposure activates microglia to produce and secrete CIRP and possibly induce pro-inflammatory response and thereby causing neuroinflammation.CIRP could be a novel mediator of alcohol-induced brain inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, United States of America.

ABSTRACT
Binge drinking has been associated with cerebral dysfunction. Ethanol induced microglial activation initiates an inflammatory process that causes upregulation of proinflammatory cytokines which in turn creates neuronal inflammation and damage. However, the molecular mechanism is not fully understood. We postulate that cold-inducible RNA-binding protein (CIRP), a novel proinflammatory molecule, can contribute to alcohol-induced neuroinflammation. To test this theory male wild-type (WT) mice were exposed to alcohol at concentrations consistent to binge drinking and blood and brain tissues were collected. At 5 h after alcohol, a significant increase of 53% in the brain of CIRP mRNA was observed and its expression remained elevated at 10 h and 15 h. Brain CIRP protein levels were increased by 184% at 10 h and remained high at 15 h. We then exposed male WT and CIRP knockout (CIRP(-/-)) mice to alcohol, and blood and brain tissues were collected at 15 h post-alcohol infusion. Serum levels of tissue injury markers (AST, ALT and LDH) were significantly elevated in alcohol-exposed WT mice while they were less increased in the CIRP(-/-) mice. Brain TNF-α mRNA and protein expressions along with IL-1β protein levels were significantly increased in WT mice, which was not seen in the CIRP(-/-) mice. In cultured BV2 cells (mouse microglia), ethanol at 100 mM showed an increase of CIRP mRNA by 274% and 408% at 24 h and 48 h respectively. Corresponding increases in TNF-α and IL-1β were also observed. CIRP protein levels were markedly increased in the medium, suggesting that CIRP was secreted by the BV2 cells. From this we conclude that alcohol exposure activates microglia to produce and secrete CIRP and possibly induce pro-inflammatory response and thereby causing neuroinflammation. CIRP could be a novel mediator of alcohol-induced brain inflammation.

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Clinical markers of organ injury were improved in CIRP−/− following alcohol exposure.WT and CIRP−/− mice were infused intravenously with alcohol for 15 h. Serum was collected and analyzed for AST (A), ALT (B) and LDH (C) using standardized assays. Data are presented as means ± SE (n = 5/group) and compared by one-way ANOVA and SNK method; *p<0.05 vs. respective Sham and #p<0.05 vs. WT alcohol group.
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pone-0079430-g002: Clinical markers of organ injury were improved in CIRP−/− following alcohol exposure.WT and CIRP−/− mice were infused intravenously with alcohol for 15 h. Serum was collected and analyzed for AST (A), ALT (B) and LDH (C) using standardized assays. Data are presented as means ± SE (n = 5/group) and compared by one-way ANOVA and SNK method; *p<0.05 vs. respective Sham and #p<0.05 vs. WT alcohol group.

Mentions: To delineate the importance of the increased CIRP expression in the brain, we evaluated the effects of alcohol on mice in the absence of the CIRP protein. WT and CIRP−/− mice were infused intravenously with alcohol for 15 h as previously described. As systemic markers of organ injury, serum levels of enzymes AST, ALT and LDH were measured. Alcohol infusion in the WT animals caused significant increases of 467%, 157% and 321% in serum AST, ALT and LDH respectively (Figs. 2A–C). In the CIRP−/− mice, these values were decreased by 66%, 42% and 47% respectively, when compared to the alcohol-exposed WT mice, indicating a significantly decreased degree of tissue injury (Figs. 2A–C). We also measured AST, ALT and LDH at 5 h and 10 h after alcohol infusion in the WT mice. All three parameters increased with time after the start of the alcohol infusion (Table 3).


Cold-inducible RNA-binding protein is an important mediator of alcohol-induced brain inflammation.

Rajayer SR, Jacob A, Yang WL, Zhou M, Chaung W, Wang P - PLoS ONE (2013)

Clinical markers of organ injury were improved in CIRP−/− following alcohol exposure.WT and CIRP−/− mice were infused intravenously with alcohol for 15 h. Serum was collected and analyzed for AST (A), ALT (B) and LDH (C) using standardized assays. Data are presented as means ± SE (n = 5/group) and compared by one-way ANOVA and SNK method; *p<0.05 vs. respective Sham and #p<0.05 vs. WT alcohol group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815202&req=5

pone-0079430-g002: Clinical markers of organ injury were improved in CIRP−/− following alcohol exposure.WT and CIRP−/− mice were infused intravenously with alcohol for 15 h. Serum was collected and analyzed for AST (A), ALT (B) and LDH (C) using standardized assays. Data are presented as means ± SE (n = 5/group) and compared by one-way ANOVA and SNK method; *p<0.05 vs. respective Sham and #p<0.05 vs. WT alcohol group.
Mentions: To delineate the importance of the increased CIRP expression in the brain, we evaluated the effects of alcohol on mice in the absence of the CIRP protein. WT and CIRP−/− mice were infused intravenously with alcohol for 15 h as previously described. As systemic markers of organ injury, serum levels of enzymes AST, ALT and LDH were measured. Alcohol infusion in the WT animals caused significant increases of 467%, 157% and 321% in serum AST, ALT and LDH respectively (Figs. 2A–C). In the CIRP−/− mice, these values were decreased by 66%, 42% and 47% respectively, when compared to the alcohol-exposed WT mice, indicating a significantly decreased degree of tissue injury (Figs. 2A–C). We also measured AST, ALT and LDH at 5 h and 10 h after alcohol infusion in the WT mice. All three parameters increased with time after the start of the alcohol infusion (Table 3).

Bottom Line: At 5 h after alcohol, a significant increase of 53% in the brain of CIRP mRNA was observed and its expression remained elevated at 10 h and 15 h.From this we conclude that alcohol exposure activates microglia to produce and secrete CIRP and possibly induce pro-inflammatory response and thereby causing neuroinflammation.CIRP could be a novel mediator of alcohol-induced brain inflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, United States of America.

ABSTRACT
Binge drinking has been associated with cerebral dysfunction. Ethanol induced microglial activation initiates an inflammatory process that causes upregulation of proinflammatory cytokines which in turn creates neuronal inflammation and damage. However, the molecular mechanism is not fully understood. We postulate that cold-inducible RNA-binding protein (CIRP), a novel proinflammatory molecule, can contribute to alcohol-induced neuroinflammation. To test this theory male wild-type (WT) mice were exposed to alcohol at concentrations consistent to binge drinking and blood and brain tissues were collected. At 5 h after alcohol, a significant increase of 53% in the brain of CIRP mRNA was observed and its expression remained elevated at 10 h and 15 h. Brain CIRP protein levels were increased by 184% at 10 h and remained high at 15 h. We then exposed male WT and CIRP knockout (CIRP(-/-)) mice to alcohol, and blood and brain tissues were collected at 15 h post-alcohol infusion. Serum levels of tissue injury markers (AST, ALT and LDH) were significantly elevated in alcohol-exposed WT mice while they were less increased in the CIRP(-/-) mice. Brain TNF-α mRNA and protein expressions along with IL-1β protein levels were significantly increased in WT mice, which was not seen in the CIRP(-/-) mice. In cultured BV2 cells (mouse microglia), ethanol at 100 mM showed an increase of CIRP mRNA by 274% and 408% at 24 h and 48 h respectively. Corresponding increases in TNF-α and IL-1β were also observed. CIRP protein levels were markedly increased in the medium, suggesting that CIRP was secreted by the BV2 cells. From this we conclude that alcohol exposure activates microglia to produce and secrete CIRP and possibly induce pro-inflammatory response and thereby causing neuroinflammation. CIRP could be a novel mediator of alcohol-induced brain inflammation.

Show MeSH
Related in: MedlinePlus