Keap1 silencing boosts lipopolysaccharide-induced transcription of interleukin 6 via activation of nuclear factor κB in macrophages

Toxicology and Applied Pharmacology

Volumn 272, Issue 3, 2013, Pages 697-702

  Lv, Peng ^a,b   Xue, Peng ^b   Dong, Jian ^b   Peng, Hui ^b,c   Clewell, Rebecca ^b   Wang, Aiping ^a   Wang, Yue ^d   Peng, Shuangqing ^c   Qu, Weidong ^e   Zhang, Qiang ^b   Andersen, Melvin E ^b   Pi, Jingbo ^b  

^a INSTITUTE OF MATERIA MEDICA   (China)

^b HAMNER INSTITUTES FOR HEALTH SCIENCES   (United States)

^c BEIJING INSTITUTE OF MICROBIOLOGY AND EPIDEMIOLOGY   (China)

^d NATIONAL INSTITUTES FOR FOOD AND DRUG CONTROL   (China)

^e FUDAN UNIVERSITY   (China)

Author keywords

IKK ; IL6; Keap1; Macrophage; NF B; Nrf2

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; KELCH LIKE ECH ASSOCIATED PROTEIN 1; LIPOPOLYSACCHARIDE; TERT BUTYLHYDROQUINONE; TRANSCRIPTION FACTOR NRF2;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; HUMAN; HUMAN CELL; MACROPHAGE; MONOCYTE; MOUSE; NONHUMAN; PHENOTYPE; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN SECRETION; TRANSACTIVATION;

IKKΒ; IL6; KEAP1; MACROPHAGE; NF-ΚB; NRF2;

ANIMALS; CELL LINE; CELL LINE, TUMOR; GENE SILENCING; HUMANS; INTERLEUKIN-6; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LIPOPOLYSACCHARIDES; MACROPHAGES; MICE; NF-KAPPA B; TRANSCRIPTION, GENETIC; UP-REGULATION;

EID: 84884691941     PISSN: 0041008X     EISSN: 10960333     Source Type: Journal    
DOI: 10.1016/j.taap.2013.07.012     Document Type: Article

References (49)

1. Baeuerle P.A., Baltimore D. NF-kappa B: ten years after. Cell 1996, 87:13-20.
2. Brasier A.R. The nuclear factor-kappaB-interleukin-6 signalling pathway mediating vascular inflammation. Cardiovasc. Res. 2010, 86:211-218.
3. Cho H.Y., Kleeberger S.R. Nrf2 protects against airway disorders. Toxicol. Appl. Pharmacol. 2010, 244:43-56.
4. Dendorfer U., Oettgen P., Libermann T.A. Multiple regulatory elements in the interleukin-6 gene mediate induction by prostaglandins, cyclic AMP, and lipopolysaccharide. Mol. Cell. Biol. 1994, 14:4443-4454.
5. Gabay C. Interleukin-6 and chronic inflammation. Arthritis Res. Ther. 2006, 8(Suppl. 2):S3.
6. Giudice A., Arra C., Turco M.C. Review of molecular mechanisms involved in the activation of the Nrf2-ARE signaling pathway by chemopreventive agents. Methods Mol. Biol. 2010, 647:37-74.
7. Hayden M.S., Ghosh S. Shared principles in NF-kappaB signaling. Cell 2008, 132:344-362.
8. Hayes J.D., McMahon M. NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem. Sci. 2009, 34:176-188.
9. Hou Y., Xue P., Bai Y., Liu D., Woods C.G., Yarborough K., Fu J., Zhang Q., Sun G., Collins S., Chan J.Y., Yamamoto M., Andersen M.E., Pi J. Nuclear factor erythroid-derived factor 2-related factor 2 regulates transcription of CCAAT/enhancer-binding protein beta during adipogenesis. Free Radic. Biol. Med. 2012, 52:462-472.
10. Jin W., Wang H., Ji Y., Hu Q., Yan W., Chen G., Yin H. Increased intestinal inflammatory response and gut barrier dysfunction in Nrf2-deficient mice after traumatic brain injury. Cytokine 2008, 44:135-140.
11. Jin W., Wang H., Yan W., Xu L., Wang X., Zhao X., Yang X., Chen G., Ji Y. Disruption of Nrf2 enhances upregulation of nuclear factor-kappaB activity, proinflammatory cytokines, and intercellular adhesion molecule-1 in the brain after traumatic brain injury. Mediators Inflamm. 2008, 2008:725174.
12. Jin W., Zhu L., Guan Q., Chen G., Wang Q.F., Yin H.X., Hang C.H., Shi J.X., Wang H.D. Influence of Nrf2 genotype on pulmonary NF-kappaB activity and inflammatory response after traumatic brain injury. Ann. Clin. Lab. Sci. 2008, 38:221-227.
13. Kim J.E., You D.J., Lee C., Ahn C., Seong J.Y., Hwang J.I. Suppression of NF-kappaB signaling by KEAP1 regulation of IKKbeta activity through autophagic degradation and inhibition of phosphorylation. Cell. Signal. 2010, 22:1645-1654.
14. Kishimoto T. Interleukin-6: from basic science to medicine-40years in immunology. Annu. Rev. Immunol. 2005, 23:1-21.
15. Kobayashi A., Kang M.I., Okawa H., Ohtsuji M., Zenke Y., Chiba T., Igarashi K., Yamamoto M. Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol. Cell. Biol. 2004, 24:7130-7139.
16. Kong X., Thimmulappa R., Craciun F., Harvey C., Singh A., Kombairaju P., Reddy S.P., Remick D., Biswal S. Enhancing Nrf2 pathway by disruption of Keap1 in myeloid leukocytes protects against sepsis. Am. J. Respir. Crit. Care Med. 2011, 184:928-938.
17. Kundu J.K., Surh Y.J. Emerging avenues linking inflammation and cancer. Free Radic. Biol. Med. 2012, 52:2013-2037.
18. Lee D.F., Kuo H.P., Liu M., Chou C.K., Xia W., Du Y., Shen J., Chen C.T., Huo L., Hsu M.C., Li C.W., Ding Q., Liao T.L., Lai C.C., Lin A.C., Chang Y.H., Tsai S.F., Li L.Y., Hung M.C. KEAP1 E3 ligase-mediated downregulation of NF-kappaB signaling by targeting IKKbeta. Mol. Cell 2009, 36:131-140.
19. Lin W., Wu R.T., Wu T., Khor T.O., Wang H., Kong A.N. Sulforaphane suppressed LPS-induced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway. Biochem. Pharmacol. 2008, 76:967-973.
20. Liu G.H., Qu J., Shen X. NF-kappaB/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK. Biochim. Biophys. Acta 2008, 1783:713-727.
21. Lu Y.C., Kim I., Lye E., Shen F., Suzuki N., Suzuki S., Gerondakis S., Akira S., Gaffen S.L., Yeh W.C., Ohashi P.S. Differential role for c-Rel and C/EBPbeta/delta in TLR-mediated induction of proinflammatory cytokines. J. Immunol. 2009, 182:7212-7221.
22. Maher J., Yamamoto M. The rise of antioxidant signaling-the evolution and hormetic actions of Nrf2. Toxicol. Appl. Pharmacol. 2010, 244:4-15.
23. More V.R., Xu J., Shimpi P.C., Belgrave C., Luyendyk J.P., Yamamoto M., Slitt A.L. Keap1 Knockdown increases markers of metabolic syndrome after long-term high fat diet feeding. Free Radic. Biol. Med. 2013, 61C:85-94.
24. Nagai N., Thimmulappa R.K., Cano M., Fujihara M., Izumi-Nagai K., Kong X., Sporn M.B., Kensler T.W., Biswal S., Handa J.T. Nrf2 is a critical modulator of the innate immune response in a model of uveitis. Free Radic. Biol. Med. 2009, 47:300-306.
25. Nilsson R., Bajic V.B., Suzuki H., di Bernardo D., Bjorkegren J., Katayama S., Reid J.F., Sweet M.J., Gariboldi M., Carninci P., Hayashizaki Y., Hume D.A., Tegner J., Ravasi T. Transcriptional network dynamics in macrophage activation. Genomics 2006, 88:133-142.
26. Niture S.K., Khatri R., Jaiswal A.K. Regulation of Nrf2-an update. Free Radic. Biol. Med. 2013, pii: S0891-5849(13)00061-0.
27. Odegaard J.I., Chawla A. Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis. Science 2013, 339:172-177.
28. Plaisance S., Vanden Berghe W., Boone E., Fiers W., Haegeman G. Recombination signal sequence binding protein Jkappa is constitutively bound to the NF-kappaB site of the interleukin-6 promoter and acts as a negative regulatory factor. Mol. Cell. Biol. 1997, 17:3733-3743.
29. Reddy N.M., Suryanarayana V., Kalvakolanu D.V., Yamamoto M., Kensler T.W., Hassoun P.M., Kleeberger S.R., Reddy S.P. Innate immunity against bacterial infection following hyperoxia exposure is impaired in NRF2-deficient mice. J. Immunol. 2009, 183:4601-4608.
30. Roach J.C., Smith K.D., Strobe K.L., Nissen S.M., Haudenschild C.D., Zhou D., Vasicek T.J., Held G.A., Stolovitzky G.A., Hood L.E., Aderem A. Transcription factor expression in lipopolysaccharide-activated peripheral-blood-derived mononuclear cells. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:16245-16250.
31. Schuett H., Luchtefeld M., Grothusen C., Grote K., Schieffer B. How much is too much? Interleukin-6 and its signalling in atherosclerosis. Thromb. Haemost. 2009, 102:215-222.
32. Soetikno V., Sari F.R., Lakshmanan A.P., Arumugam S., Harima M., Suzuki K., Kawachi H., Watanabe K. Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap1 pathway. Mol. Nutr. Food Res 2012, 10.1002/mnfr.201200540.
33. Thimmulappa R.K., Lee H., Rangasamy T., Reddy S.P., Yamamoto M., Kensler T.W., Biswal S. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J. Clin. Invest. 2006, 116:984-995.
34. Thimmulappa R.K., Scollick C., Traore K., Yates M., Trush M.A., Liby K.T., Sporn M.B., Yamamoto M., Kensler T.W., Biswal S. Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem. Biophys. Res. Commun. 2006, 351:883-889.
35. Thu K.L., Pikor L.A., Chari R., Wilson I.M., Macaulay C.E., English J.C., Tsao M.S., Gazdar A.F., Lam S., Lam W.L., Lockwood W.W. Genetic disruption of KEAP1/CUL3 E3 ubiquitin ligase complex components is a key mechanism of NF-kappaB pathway activation in lung cancer. J. Thorac. Oncol. 2011, 6:1521-1529.
36. Wakabayashi N., Itoh K., Wakabayashi J., Motohashi H., Noda S., Takahashi S., Imakado S., Kotsuji T., Otsuka F., Roop D.R., Harada T., Engel J.D., Yamamoto M. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat. Genet. 2003, 35:238-245.
37. Wang X.J., Sun Z., Villeneuve N.F., Zhang S., Zhao F., Li Y., Chen W., Yi X., Zheng W., Wondrak G.T., Wong P.K., Zhang D.D. Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis 2008, 29:1235-1243.
38. Wongchana W., Palaga T. Direct regulation of interleukin-6 expression by Notch signaling in macrophages. Cell. Mol. Immunol. 2012, 9:155-162.
39. Woods C.G., Fu J., Xue P., Hou Y., Pluta L.J., Yang L., Zhang Q., Thomas R.S., Andersen M.E., Pi J. Dose-dependent transitions in Nrf2-mediated adaptive response and related stress responses to hypochlorous acid in mouse macrophages. Toxicol. Appl. Pharmacol. 2009, 238:27-36.
40. Wruck C.J., Streetz K., Pavic G., Gotz M.E., Tohidnezhad M., Brandenburg L.O., Varoga D., Eickelberg O., Herdegen T., Trautwein C., Cha K., Kan Y.W., Pufe T. Nrf2 induces interleukin-6 (IL-6) expression via an antioxidant response element within the IL-6 promoter. J. Biol. Chem. 2011, 286:4493-4499.
41. Xiao W., Hodge D.R., Wang L., Yang X., Zhang X., Farrar W.L. Co-operative functions between nuclear factors NFkappaB and CCAT/enhancer-binding protein-beta (C/EBP-beta) regulate the IL-6 promoter in autocrine human prostate cancer cells. Prostate 2004, 61:354-370.
42. Yang B., Fu J., Zheng H., Xue P., Yarborough K., Woods C.G., Hou Y., Zhang Q., Andersen M.E., Pi J. Deficiency in the nuclear factor E2-related factor 2 renders pancreatic beta-cells vulnerable to arsenic-induced cell damage. Toxicol. Appl. Pharmacol. 2012, 264:315-323.
43. Yu M., Li H., Liu Q., Liu F., Tang L., Li C., Yuan Y., Zhan Y., Xu W., Li W., Chen H., Ge C., Wang J., Yang X. Nuclear factor p65 interacts with Keap1 to repress the Nrf2-ARE pathway. Cell. Signal. 2011, 23:883-892.
44. Zhan L., Zhang H., Zhang Q., Woods C.G., Chen Y., Xue P., Dong J., Tokar E.J., Xu Y., Hou Y., Fu J., Yarborough K., Wang A., Qu W., Waalkes M.P., Andersen M.E., Pi J. Regulatory role of KEAP1 and NRF2 in PPARgamma expression and chemoresistance in human non-small-cell lung carcinoma cells. Free Radic. Biol. Med. 2012, 53:758-768.
45. Zhang G., Ghosh S. Molecular mechanisms of NF-kappaB activation induced by bacterial lipopolysaccharide through Toll-like receptors. J. Endotoxin Res. 2000, 6:453-457.
46. Zhang G., Ghosh S. Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity. J. Clin. Invest. 2001, 107:13-19.
47. Zhang D.D., Lo S.C., Cross J.V., Templeton D.J., Hannink M. Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Mol. Cell. Biol. 2004, 24:10941-10953.
48. Zhang C., Bai N., Chang A., Zhang Z., Yin J., Shen W., Tian Y., Xiang R., Liu C. ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes. Cell. Mol. Immunol. 2013, 10:84-94.
49. Zhao R., Hou Y., Zhang Q., Woods C.G., Xue P., Fu J., Yarborough K., Guan D., Andersen M.E., Pi J. Cross-regulations among NRFs and KEAP1 and effects of their silencing on arsenic-induced antioxidant response and cytotoxicity in human keratinocytes. Environ. Health Perspect. 2012, 120:583-589.