Skip to main content
Erschienen in: Inflammation 6/2016

02.09.2016 | ORIGINAL ARTICLE

Reduced Expression of SARM in Mouse Spleen during Polymicrobial Sepsis

verfasst von: Yu Gong, Lin Zou, Dongzhi Cen, Wei Chao, Dunjin Chen

Erschienen in: Inflammation | Ausgabe 6/2016

Einloggen, um Zugang zu erhalten

Abstract

Objective Immune dysfunction, including prominent apoptosis of immune cells and decreased functioning of the remaining immune cells, plays a central role in the pathogenesis of sepsis. Sterile α and HEAT/armadillo motif-containing protein (SARM) is implicated in the regulation of immune cell apoptosis. This study aimed to elucidate SARM contributes to sepsis-induced immune cell death and immunosuppression. Methods A mouse model of polymicrobial sepsis was generated by cecum ligation and puncture (CLP). SARM gene and protein expression, caspase 3 cleavage and intracellular ATP production were measured in the mouse spleens. Results CLP-induced polymicrobial sepsis specifically attenuated both the gene and protein expression of SARM in the spleens. Moreover, the attenuation of SARM expression synchronized with splenocyte apoptosis, as evidenced by increased caspase 3 cleavage and ATP depletion. Conclusions These findings suggest that SARM is a potential regulator of sepsis-induced splenocyte apoptosis.
Literatur
2.
Zurück zum Zitat Mayr, F.B., S. Yende, and D.C. Angus. 2014. Epidemiology of severe sepsis. Virulence 5: 4–11.CrossRefPubMed Mayr, F.B., S. Yende, and D.C. Angus. 2014. Epidemiology of severe sepsis. Virulence 5: 4–11.CrossRefPubMed
3.
Zurück zum Zitat Zhou, J., C. Qian, M. Zhao, X. Yu, Y. Kang, X. Ma, et al. 2014. Epidemiology and outcome of severe sepsis and septic shock in intensive care units in mainland China. PloS One 9: e107181.CrossRefPubMedPubMedCentral Zhou, J., C. Qian, M. Zhao, X. Yu, Y. Kang, X. Ma, et al. 2014. Epidemiology and outcome of severe sepsis and septic shock in intensive care units in mainland China. PloS One 9: e107181.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Leentjens, J., M. Kox, J.G. van der Hoeven, M.G. Netea, and P. Pickkers. 2013. Immunotherapy for the adjunctive treatment of sepsis: from immunosuppression to immunostimulation. Time for a paradigm change? American Journal of Respiratory and Critical Care Medicine 187: 1287–1293.CrossRefPubMed Leentjens, J., M. Kox, J.G. van der Hoeven, M.G. Netea, and P. Pickkers. 2013. Immunotherapy for the adjunctive treatment of sepsis: from immunosuppression to immunostimulation. Time for a paradigm change? American Journal of Respiratory and Critical Care Medicine 187: 1287–1293.CrossRefPubMed
5.
Zurück zum Zitat Hotchkiss, R.S., G. Monneret, and D. Payen. 2013. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. Lancet Infectious Diseases 13: 260–268.CrossRefPubMed Hotchkiss, R.S., G. Monneret, and D. Payen. 2013. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. Lancet Infectious Diseases 13: 260–268.CrossRefPubMed
6.
Zurück zum Zitat Hotchkiss, R.S., G. Monneret, and D. Payen. 2013. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nature Reviews Immunology 13: 862–874.CrossRefPubMedPubMedCentral Hotchkiss, R.S., G. Monneret, and D. Payen. 2013. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nature Reviews Immunology 13: 862–874.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Condotta, S.A., J. Cabrera-Perez, V.P. Badovinac, and T.S. Griffith. 2013. T-cell-mediated immunity and the role of TRAIL in sepsis-induced immunosuppression. Critical Reviews in Immunology 33: 23–40.CrossRefPubMedPubMedCentral Condotta, S.A., J. Cabrera-Perez, V.P. Badovinac, and T.S. Griffith. 2013. T-cell-mediated immunity and the role of TRAIL in sepsis-induced immunosuppression. Critical Reviews in Immunology 33: 23–40.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Mink, M., B. Fogelgren, K. Olszewski, P. Maroy, and K. Csiszar. 2001. A novel human gene (SARM) at chromosome 17q11 encodes a protein with a SAM motif and structural similarity to Armadillo/beta-catenin that is conserved in mouse, Drosophila, and Caenorhabditis elegans. Genomics 74: 234–244.CrossRefPubMed Mink, M., B. Fogelgren, K. Olszewski, P. Maroy, and K. Csiszar. 2001. A novel human gene (SARM) at chromosome 17q11 encodes a protein with a SAM motif and structural similarity to Armadillo/beta-catenin that is conserved in mouse, Drosophila, and Caenorhabditis elegans. Genomics 74: 234–244.CrossRefPubMed
9.
Zurück zum Zitat O’Neill, L.A., K.A. Fitzgerald, and A.G. Bowie. 2003. The Toll-IL-1 receptor adaptor family grows to five members. Trends in Immunology 24: 286–290.CrossRefPubMed O’Neill, L.A., K.A. Fitzgerald, and A.G. Bowie. 2003. The Toll-IL-1 receptor adaptor family grows to five members. Trends in Immunology 24: 286–290.CrossRefPubMed
10.
Zurück zum Zitat O’Neill, L.A., and A.G. Bowie. 2007. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nature Reviews Immunology 7: 353–364.CrossRefPubMed O’Neill, L.A., and A.G. Bowie. 2007. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nature Reviews Immunology 7: 353–364.CrossRefPubMed
11.
Zurück zum Zitat Kim, Y., P. Zhou, L. Qian, J.Z. Chuang, J. Lee, C. Li, et al. 2007. MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival. Journal of Experimental Medicine 204: 2063–2074.CrossRefPubMedPubMedCentral Kim, Y., P. Zhou, L. Qian, J.Z. Chuang, J. Lee, C. Li, et al. 2007. MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival. Journal of Experimental Medicine 204: 2063–2074.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Mukherjee, P., T.A. Woods, R.A. Moore, and K.E. Peterson. 2013. Activation of the innate signaling molecule MAVS by bunyavirus infection upregulates the adaptor protein SARM1, leading to neuronal death. Immunity 38: 705–716.CrossRefPubMedPubMedCentral Mukherjee, P., T.A. Woods, R.A. Moore, and K.E. Peterson. 2013. Activation of the innate signaling molecule MAVS by bunyavirus infection upregulates the adaptor protein SARM1, leading to neuronal death. Immunity 38: 705–716.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Panneerselvam, P., L.P. Singh, B. Ho, J. Chen, and J.L. Ding. 2012. Targeting of pro-apoptotic TLR adaptor SARM to mitochondria: definition of the critical region and residues in the signal sequence. Biometrical Journal 442: 263–271. Panneerselvam, P., L.P. Singh, B. Ho, J. Chen, and J.L. Ding. 2012. Targeting of pro-apoptotic TLR adaptor SARM to mitochondria: definition of the critical region and residues in the signal sequence. Biometrical Journal 442: 263–271.
14.
Zurück zum Zitat Panneerselvam, P., L.P. Singh, V. Selvarajan, W.J. Chng, S.B. Ng, N.S. Tan, et al. 2013. T-cell death following immune activation is mediated by mitochondria-localized SARM. Cell Death and Differentiation 20: 478–489.CrossRefPubMed Panneerselvam, P., L.P. Singh, V. Selvarajan, W.J. Chng, S.B. Ng, N.S. Tan, et al. 2013. T-cell death following immune activation is mediated by mitochondria-localized SARM. Cell Death and Differentiation 20: 478–489.CrossRefPubMed
15.
Zurück zum Zitat Sethman, C.R., and J. Hawiger. 2013. The innate immunity adaptor SARM translocates to the nucleus to stabilize lamins and prevent DNA fragmentation in response to pro-apoptotic signaling. PLoS One 8: e70994.CrossRefPubMedPubMedCentral Sethman, C.R., and J. Hawiger. 2013. The innate immunity adaptor SARM translocates to the nucleus to stabilize lamins and prevent DNA fragmentation in response to pro-apoptotic signaling. PLoS One 8: e70994.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Wichterman, K.A., A.E. Baue, and I.H. Chaudry. 1980. Sepsis and septic shock—a review of laboratory models and a proposal. Journal of Surgical Research 29: 189–201.CrossRefPubMed Wichterman, K.A., A.E. Baue, and I.H. Chaudry. 1980. Sepsis and septic shock—a review of laboratory models and a proposal. Journal of Surgical Research 29: 189–201.CrossRefPubMed
17.
Zurück zum Zitat Zou, L., Y. Feng, Y.J. Chen, R. Si, S. Shen, Q. Zhou, et al. 2010. Toll-like receptor 2 plays a critical role in cardiac dysfunction during polymicrobial sepsis. Critical Care Medicine 38: 1335–1342.CrossRefPubMedPubMedCentral Zou, L., Y. Feng, Y.J. Chen, R. Si, S. Shen, Q. Zhou, et al. 2010. Toll-like receptor 2 plays a critical role in cardiac dysfunction during polymicrobial sepsis. Critical Care Medicine 38: 1335–1342.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Zou, L., Y. Feng, Y. Li, M. Zhang, C. Chen, J. Cai, et al. 2013. Complement factor B is the downstream effector of TLRs and plays an important role in a mouse model of severe sepsis. Journal of Immunology 191: 5625–5635.CrossRef Zou, L., Y. Feng, Y. Li, M. Zhang, C. Chen, J. Cai, et al. 2013. Complement factor B is the downstream effector of TLRs and plays an important role in a mouse model of severe sepsis. Journal of Immunology 191: 5625–5635.CrossRef
19.
Zurück zum Zitat Zou, L., Y. Feng, M. Zhang, Y. Li, and W. Chao. 2011. Nonhematopoietic toll-like receptor 2 contributes to neutrophil and cardiac function impairment during polymicrobial sepsis. Shock 36: 370–380.CrossRefPubMedPubMedCentral Zou, L., Y. Feng, M. Zhang, Y. Li, and W. Chao. 2011. Nonhematopoietic toll-like receptor 2 contributes to neutrophil and cardiac function impairment during polymicrobial sepsis. Shock 36: 370–380.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Schmittgen, T.D., and K.J. Livak. 2008. Analyzing real-time PCR data by the comparative C(T) method. Nature Protocols 3: 1101–1108.CrossRefPubMed Schmittgen, T.D., and K.J. Livak. 2008. Analyzing real-time PCR data by the comparative C(T) method. Nature Protocols 3: 1101–1108.CrossRefPubMed
21.
Zurück zum Zitat Livak, K.J., and T.D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402–408.CrossRefPubMed Livak, K.J., and T.D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402–408.CrossRefPubMed
22.
Zurück zum Zitat Poli-de-Figueiredo, L.F., A.G. Garrido, N. Nakagawa, and P. Sannomiya. 2008. Experimental models of sepsis and their clinical relevance. Shock 30(Suppl 1): 53–59.CrossRefPubMed Poli-de-Figueiredo, L.F., A.G. Garrido, N. Nakagawa, and P. Sannomiya. 2008. Experimental models of sepsis and their clinical relevance. Shock 30(Suppl 1): 53–59.CrossRefPubMed
23.
Zurück zum Zitat Carty, M., R. Goodbody, M. Schroder, J. Stack, P.N. Moynagh, and A.G. Bowie. 2006. The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nature Immunology 7: 1074–1081.CrossRefPubMed Carty, M., R. Goodbody, M. Schroder, J. Stack, P.N. Moynagh, and A.G. Bowie. 2006. The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nature Immunology 7: 1074–1081.CrossRefPubMed
24.
Zurück zum Zitat Belinda, L.W., W.X. Wei, B.T. Hanh, L.X. Lei, H. Bow, and D.J. Ling. 2008. SARM: a novel Toll-like receptor adaptor, is functionally conserved from arthropod to human. Molecular Immunology 45: 1732–1742.CrossRefPubMed Belinda, L.W., W.X. Wei, B.T. Hanh, L.X. Lei, H. Bow, and D.J. Ling. 2008. SARM: a novel Toll-like receptor adaptor, is functionally conserved from arthropod to human. Molecular Immunology 45: 1732–1742.CrossRefPubMed
25.
Zurück zum Zitat Peng, J., Q. Yuan, B. Lin, P. Panneerselvam, X. Wang, X.L. Luan, et al. 2010. SARM inhibits both TRIF- and MyD88-mediated AP-1 activation. European Journal of Immunology 40: 1738–1747.CrossRefPubMed Peng, J., Q. Yuan, B. Lin, P. Panneerselvam, X. Wang, X.L. Luan, et al. 2010. SARM inhibits both TRIF- and MyD88-mediated AP-1 activation. European Journal of Immunology 40: 1738–1747.CrossRefPubMed
26.
Zurück zum Zitat Hou, Y.J., R. Banerjee, B. Thomas, C. Nathan, A. Garcia-Sastre, A. Ding, et al. 2013. SARM is required for neuronal injury and cytokine production in response to central nervous system viral infection. Journal of Immunology 191: 875–883.CrossRef Hou, Y.J., R. Banerjee, B. Thomas, C. Nathan, A. Garcia-Sastre, A. Ding, et al. 2013. SARM is required for neuronal injury and cytokine production in response to central nervous system viral infection. Journal of Immunology 191: 875–883.CrossRef
27.
Zurück zum Zitat Gerdts, J., D.W. Summers, Y. Sasaki, A. DiAntonio, and J. Milbrandt. 2013. Sarm1-mediated axon degeneration requires both SAM and TIR interactions. Journal of Neuroscience 33: 13569–13580.CrossRefPubMedPubMedCentral Gerdts, J., D.W. Summers, Y. Sasaki, A. DiAntonio, and J. Milbrandt. 2013. Sarm1-mediated axon degeneration requires both SAM and TIR interactions. Journal of Neuroscience 33: 13569–13580.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Summers, D.W., A. DiAntonio, and J. Milbrandt. 2014. Mitochondrial dysfunction induces Sarm1-dependent cell death in sensory neurons. Journal of Neuroscience 34: 9338–9350.CrossRefPubMedPubMedCentral Summers, D.W., A. DiAntonio, and J. Milbrandt. 2014. Mitochondrial dysfunction induces Sarm1-dependent cell death in sensory neurons. Journal of Neuroscience 34: 9338–9350.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Yu, X.M., and L. Luo. 2012. Neuroscience. dSarm-ing axon degeneration. Science 337: 418–419.CrossRefPubMed Yu, X.M., and L. Luo. 2012. Neuroscience. dSarm-ing axon degeneration. Science 337: 418–419.CrossRefPubMed
30.
Zurück zum Zitat Osterloh, J.M., J. Yang, T.M. Rooney, A.N. Fox, R. Adalbert, E.H. Powell, et al. 2012. dSarm/Sarm1 is required for activation of an injury-induced axon death pathway. Science 337: 481–484.CrossRefPubMed Osterloh, J.M., J. Yang, T.M. Rooney, A.N. Fox, R. Adalbert, E.H. Powell, et al. 2012. dSarm/Sarm1 is required for activation of an injury-induced axon death pathway. Science 337: 481–484.CrossRefPubMed
31.
Zurück zum Zitat Szretter, K.J., M.A. Samuel, S. Gilfillan, A. Fuchs, M. Colonna, and M.S. Diamond. 2009. The immune adaptor molecule SARM modulates tumor necrosis factor alpha production and microglia activation in the brainstem and restricts West Nile Virus pathogenesis. Journal of Virology 83: 9329–9338.CrossRefPubMedPubMedCentral Szretter, K.J., M.A. Samuel, S. Gilfillan, A. Fuchs, M. Colonna, and M.S. Diamond. 2009. The immune adaptor molecule SARM modulates tumor necrosis factor alpha production and microglia activation in the brainstem and restricts West Nile Virus pathogenesis. Journal of Virology 83: 9329–9338.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Murata, H., M. Sakaguchi, K. Kataoka, and N.H. Huh. 2013. SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria. Molecular Biology of the Cell 24: 2772–2784.CrossRefPubMedPubMedCentral Murata, H., M. Sakaguchi, K. Kataoka, and N.H. Huh. 2013. SARM1 and TRAF6 bind to and stabilize PINK1 on depolarized mitochondria. Molecular Biology of the Cell 24: 2772–2784.CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Chang, S.C., and J.L. Ding. 2014. Ubiquitination by SAG regulates macrophage survival/death and immune response during infection. Cell Death and Differentiation 21: 1388–1398.CrossRefPubMedPubMedCentral Chang, S.C., and J.L. Ding. 2014. Ubiquitination by SAG regulates macrophage survival/death and immune response during infection. Cell Death and Differentiation 21: 1388–1398.CrossRefPubMedPubMedCentral
Metadaten
Titel
Reduced Expression of SARM in Mouse Spleen during Polymicrobial Sepsis
verfasst von
Yu Gong
Lin Zou
Dongzhi Cen
Wei Chao
Dunjin Chen
Publikationsdatum
02.09.2016
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 6/2016
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-016-0428-x

Weitere Artikel der Ausgabe 6/2016

Inflammation 6/2016 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.