|Critical Role of Toll-Like Receptor 9 in Morphine and Mycobacterium tuberculosis-Induced Apoptosis in Mice|
|Chen, Lin1,2; Shi, Wanliang3; Li, Hui1; Sun, Xiuli1,4; Fan, Xionglin3; LeSage, Gene1; Li, Hui3; Li, Yi1; Zhang, Yi1; Zhang, Xiumei2; Zhang, Ying3; Yin, Deling1|
|WOS标题词||Science & Technology|
|研究领域[WOS]||Science & Technology - Other Topics|
|关键词[WOS]||GLYCOGEN-SYNTHASE KINASE-3 ; INNATE IMMUNITY ; CELL APOPTOSIS ; INFECTION ; TLR2 ; EXPRESSION ; REGULATIONS ; RECOGNITION ; PROTEINS ; FAMILY|
Background: Although it is established that opioid and Mycobacterium tuberculosis are both public health problems, the mechanisms by which they affect lung functions remain elusive.
Methodology/Principal Findings: We report here that mice subjected to chronic morphine administration and M. tuberculosis infection exhibited significant apoptosis in the lung in wild type mice as demonstrated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. Morphine and M. tuberculosis significantly induced the expression of Toll-like receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, deficiency in TLR9 significantly inhibited the morphine and M. tuberculosis induced apoptosis in the lung. In addition, chronic morphine treatment and M. tuberculosis infection enhanced the levels of cytokines (TNF-alpha, IL-1 beta, and IL-6) in wild type mice, but not in TLR9 knockout (KO) mice. The bacterial load was much lower in TLR9 KO mice compared with that in wild type mice following morphine and M. tuberculosis treatment. Morphine alone did not alter the bacterial load in either wild type or TLR9 KO mice. Moreover, administration of morphine and M. tuberculosis decreased the levels of phosphorylation of Akt and GSK3 beta in the wild type mice, but not in TLR9 KO mice, suggesting an involvement of Akt/GSK3 beta in morphine and M. tuberculosis-mediated TLR9 signaling. Furthermore, administration of morphine and M. tuberculosis caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type mice, but not in TLR9 KO mice, indicating a role of Bcl-2 family in TLR9-mediated apoptosis in the lung following morphine and M. tuberculosis administration.
Conclusions/Significance: These data reveal a role for TLR9 in the immune response to opioids during M. tuberculosis infection.
|项目编号||DA020120-03A1 ; AI44063|
|资助机构||National Institutes of Health ; East Tennessee State University Research Development Committee ; Changjiang Scholars Program|
|作者单位||1.E Tennessee State Univ, Coll Med, Dept Internal Med, Johnson City, TN 37614 USA|
2.Shandong Univ, Sch Med, Dept Pharmacol, Jinan 250100, Peoples R China
3.Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA
4.Peking Univ, Peoples Hosp, Dept Obstet & Gynecol, Beijing 100871, Peoples R China
|Chen, Lin,Shi, Wanliang,Li, Hui,et al. Critical Role of Toll-Like Receptor 9 in Morphine and Mycobacterium tuberculosis-Induced Apoptosis in Mice[J]. PLOS ONE,2010,5(2).|
|APA||Chen, Lin.,Shi, Wanliang.,Li, Hui.,Sun, Xiuli.,Fan, Xionglin.,...&Yin, Deling.(2010).Critical Role of Toll-Like Receptor 9 in Morphine and Mycobacterium tuberculosis-Induced Apoptosis in Mice.PLOS ONE,5(2).|
|MLA||Chen, Lin,et al."Critical Role of Toll-Like Receptor 9 in Morphine and Mycobacterium tuberculosis-Induced Apoptosis in Mice".PLOS ONE 5.2(2010).|