Interleukin-27 Enhances the Potential of Reactive Oxygen Species Generation from Monocyte-derived Macrophages and Dendritic Cells by Induction of P47

Overview

Journal Sci Rep

Specialty Science

Date 2017 Feb 28

PMID 28240310

Citations 14

Authors

Bharatwaj Sowrirajan

Yoshiro Saito

Deepak Poudyal

Qian Chen

Hongyan Sui

Suk See DeRavin

Hiromi Imamichi

Toyotaka Sato

Douglas B Kuhns

Noriko Noguchi

Harry L Malech

H Clifford Lane

Tomozumi Imamichi

Affiliations

Soon will be listed here.

Abstract

Interleukin (IL)-27, a member of the IL-12 cytokine family, plays an important and diverse role in the function of the immune system. We have previously demonstrated that IL-27 is an anti-viral cytokine which inhibits HIV-1, HIV-2, Influenza virus and herpes simplex virus infection, and enhances the potential of reactive oxygen species (ROS) generating activity during differentiation of monocytes to macrophages. In this study, we further investigated the mechanism of the enhanced potential for ROS generation by IL-27. Real time PCR, western blot and knock down assays demonstrate that IL-27 is able to enhance the potential of superoxide production not only during differentiation but also in terminally differentiated-macrophages and immature dendritic cells (iDC) in association with the induction of p47, a cytosolic component of the ROS producing enzyme, NADPH oxidase, and the increase in amounts of phosphorylated p47 upon stimulation. We also demonstrate that IL-27 is able to induce extracellular superoxide dismutase during differentiation of monocytes but not in terminal differentiated macrophages. Since ROS plays an important role in a variety of inflammation, our data demonstrate that IL-27 is a potent regulator of ROS induction and may be a novel therapeutic target.

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References

Marklund S . Human copper-containing superoxide dismutase of high molecular weight. Proc Natl Acad Sci U S A. 1982; 79(24):7634-8. PMC: 347402. DOI: 10.1073/pnas.79.24.7634. View

Imlay J . Cellular defenses against superoxide and hydrogen peroxide. Annu Rev Biochem. 2008; 77:755-76. PMC: 3057177. DOI: 10.1146/annurev.biochem.77.061606.161055. View

Brown D, Griendling K . Nox proteins in signal transduction. Free Radic Biol Med. 2009; 47(9):1239-53. PMC: 2763943. DOI: 10.1016/j.freeradbiomed.2009.07.023. View

Dai L, Lidie K, Chen Q, Adelsberger J, Zheng X, Huang D . IL-27 inhibits HIV-1 infection in human macrophages by down-regulating host factor SPTBN1 during monocyte to macrophage differentiation. J Exp Med. 2013; 210(3):517-34. PMC: 3600911. DOI: 10.1084/jem.20120572. View

Elsen S, Doussiere J, Villiers C, Faure M, Berthier R, Papaioannou A . Cryptic O2- -generating NADPH oxidase in dendritic cells. J Cell Sci. 2004; 117(Pt 11):2215-26. DOI: 10.1242/jcs.01085. View

Zhao X, Carnevale K, Cathcart M . Human monocytes use Rac1, not Rac2, in the NADPH oxidase complex. J Biol Chem. 2003; 278(42):40788-92. DOI: 10.1074/jbc.M302208200. View

Xu M, Mizoguchi I, Morishima N, Chiba Y, Mizuguchi J, Yoshimoto T . Regulation of antitumor immune responses by the IL-12 family cytokines, IL-12, IL-23, and IL-27. Clin Dev Immunol. 2010; 2010. PMC: 2946577. DOI: 10.1155/2010/832454. View

Salcedo R, Hixon J, Stauffer J, Jalah R, Brooks A, Khan T . Immunologic and therapeutic synergy of IL-27 and IL-2: enhancement of T cell sensitization, tumor-specific CTL reactivity and complete regression of disseminated neuroblastoma metastases in the liver and bone marrow. J Immunol. 2009; 182(7):4328-38. PMC: 2730673. DOI: 10.4049/jimmunol.0800471. View

Groemping Y, Rittinger K . Activation and assembly of the NADPH oxidase: a structural perspective. Biochem J. 2004; 386(Pt 3):401-16. PMC: 1134858. DOI: 10.1042/BJ20041835. View

10.

Geissmann F, Manz M, Jung S, Sieweke M, Merad M, Ley K . Development of monocytes, macrophages, and dendritic cells. Science. 2010; 327(5966):656-61. PMC: 2887389. DOI: 10.1126/science.1178331. View

11.

Pflanz S, Timans J, Cheung J, Rosales R, Kanzler H, Gilbert J . IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. Immunity. 2002; 16(6):779-90. DOI: 10.1016/s1074-7613(02)00324-2. View

12.

Babior B, Lambeth J, Nauseef W . The neutrophil NADPH oxidase. Arch Biochem Biophys. 2002; 397(2):342-4. DOI: 10.1006/abbi.2001.2642. View

13.

Verreck F, de Boer T, Langenberg D, Hoeve M, Kramer M, Vaisberg E . Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. Proc Natl Acad Sci U S A. 2004; 101(13):4560-5. PMC: 384786. DOI: 10.1073/pnas.0400983101. View

14.

Gottfredsen R, Goldstrohm D, Hartney J, Larsen U, Bowler R, Petersen S . The cellular distribution of extracellular superoxide dismutase in macrophages is altered by cellular activation but unaffected by the naturally occurring R213G substitution. Free Radic Biol Med. 2014; 69:348-56. PMC: 4440334. DOI: 10.1016/j.freeradbiomed.2014.01.038. View

15.

Collison L, Vignali D . Interleukin-35: odd one out or part of the family?. Immunol Rev. 2009; 226:248-62. PMC: 2631363. DOI: 10.1111/j.1600-065X.2008.00704.x. View

16.

Hibbert L, Pflanz S, De Waal Malefyt R, Kastelein R . IL-27 and IFN-alpha signal via Stat1 and Stat3 and induce T-Bet and IL-12Rbeta2 in naive T cells. J Interferon Cytokine Res. 2003; 23(9):513-22. DOI: 10.1089/10799900360708632. View

17.

Pot C, Apetoh L, Awasthi A, Kuchroo V . Induction of regulatory Tr1 cells and inhibition of T(H)17 cells by IL-27. Semin Immunol. 2011; 23(6):438-45. PMC: 3230686. DOI: 10.1016/j.smim.2011.08.003. View

18.

Mills E, ONeill L . Reprogramming mitochondrial metabolism in macrophages as an anti-inflammatory signal. Eur J Immunol. 2015; 46(1):13-21. DOI: 10.1002/eji.201445427. View

19.

Takeda A, Hamano S, Yamanaka A, Hanada T, Ishibashi T, Mak T . Cutting edge: role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment. J Immunol. 2003; 170(10):4886-90. DOI: 10.4049/jimmunol.170.10.4886. View

20.

Hu P, Hu H, Chen M, Peng M, Tang L, Tang K . Expression of interleukins-23 and 27 leads to successful gene therapy of hepatocellular carcinoma. Mol Immunol. 2009; 46(8-9):1654-62. DOI: 10.1016/j.molimm.2009.02.025. View