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Inflammation Research

Erschienen in:

07.06.2017 | Original Research Paper

Pam2CSK4 and Pam3CSK4 induce iNOS expression via TBK1 and MyD88 molecules in mouse macrophage cell line RAW264.7

verfasst von: Panthong Kulsantiwong, Matsayapan Pudla, Chanya Srisaowakarn, Jitrada Boondit, Pongsak Utaisincharoen

Erschienen in: Inflammation Research | Ausgabe 10/2017

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Abstract

Objective

The aim of this study was to investigate the involvement of TLR adaptor molecules, such as TRIF, MyD88, and TBK1 in the induction of iNOS and nitric oxide (NO) production in Pam2CSK4 and Pam3CSK4-treated mouse macrophages.

Method

Mouse macrophage cell line (RAW264.7) was transfected with trif, myd88, and tbk1 siRNAs before stimulated with Pam2CSK4 and Pam3CSK4. The iNOS gene and protein expression were determined by RT-PCR and immunoblotting, respectively. The NO production was determined by Griess reaction assay.

Results

The results showed that the induction of iNOS expression and NO production by Pam2CSK4 and Pam3CSK4 were diminished in tbk1 and myd88-depleted mouse macrophages but not trif-depleted cells.

Conclusion

These results suggested that the TBK1 and MyD88 molecules were essential for the induction of iNOS expression and NO production by both Pam2CSK4 and Pam3CSK4 via TLR2 signaling.

Mifsud EJ, Tan AC, Jackson DC. TLR agonists as modulators of the innate immune response and their potential as agents against infectious disease. Front Immunol. 2014;5:79.CrossRefPubMedPubMedCentral

Gay NJ, Symmons MF, Gangloff M, Bryant CE. Assembly and localization of Toll-like receptor signalling complexes. Nat Rev Immunol. 2014;14:546–58.CrossRefPubMed

Medzhitov R, Janeway C Jr. Innate immune recognition: mechanisms and pathways. Immunol Rev. 2000;173:89–97.CrossRefPubMed

Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801.CrossRefPubMed

O’Neill LA, Bowie AG. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol. 2007;7:353–64.CrossRefPubMed

Akira S. Toll receptor families: structure and function. Semin Immunol. 2004;16:1–2.CrossRefPubMed

Akira S, Takeda K. Functions of toll-like receptors: lessons from KO mice. C R Biol. 2004;327:581–9.CrossRefPubMed

Albiger B, Sandgren A, Katsuragi H, Meyer-Hoffert U, Beiter K, Wartha F, et al. Myeloid differentiation factor 88-dependent signalling controls bacterial growth during colonization and systemic pneumococcal disease in mice. Cell Microbiol. 2005;7:1603–15.CrossRefPubMed

Wiersinga WJ, Wieland CW, Roelofs JJ, van der Poll T. MyD88 dependent signaling contributes to protective host defense against Burkholderia pseudomallei. PLoS ONE. 2008;3:e3494.CrossRefPubMedPubMedCentral

10.

Russo BC, Brown MJ, Nau GJ. MyD88-dependent signaling prolongs survival and reduces bacterial burden during pulmonary infection with virulent Francisella tularensis. Am J Pathol. 2013;183:1223–32.CrossRefPubMedPubMedCentral

11.

Kagan JC, Su T, Horng T, Chow A, Akira S, Medzhitov R. TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta. Nat Immunol. 2008;9:361–8.CrossRefPubMedPubMedCentral

12.

Nilsen NJ, Vladimer GI, Stenvik J, Oming MP, Zeid-Kilani MV, Bugge M, et al. A role for the adaptor proteins TRAM and TRIF in toll-like receptor 2 signaling. J Biol Chem. 2015;290:3209–22.CrossRefPubMed

13.

Ullah MO, Sweet MJ, Mansell A, Kellie S, Kobe B. TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target. J Leukoc Biol. 2016;100:27–45.CrossRefPubMed

14.

Utaisincharoen P, Anuntagool N, Arjcharoen S, Limposuwan K, Chaisuriya P, Sirisinha S. Induction of iNOS expression and antimicrobial activity by interferon (IFN)-beta is distinct from IFN-gamma in Burkholderia pseudomallei-infected mouse macrophages. Clin Exp Immunol. 2004;136:277–83.CrossRefPubMedPubMedCentral

15.

Brennan RE, Russell K, Zhang G, Samuel JE. Both inducible nitric oxide synthase and NADPH oxidase contribute to the control of virulent phase I Coxiella burnetii infections. Infect Immun. 2004;72:6666–75.CrossRefPubMedPubMedCentral

16.

Pietrocola G, Arciola CR, Rindi S, Di Poto A, Missineo A, Montanaro L, et al. Toll-like receptors (TLRs) in innate immune defense against Staphylococcus aureus. Int J Artif Organs. 2011;34:799–810.CrossRefPubMed

17.

Lu YC, Yeh WC, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine. 2008;42:145–51.CrossRefPubMed

18.

Buwitt-Beckmann U, Heine H, Wiesmuller KH, Jung G, Brock R, Akira S, et al. TLR1- and TLR6-independent recognition of bacterial lipopeptides. J Biol Chem. 2006;281:9049–57.CrossRefPubMed

19.

Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong Z, et al. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol. 2002;169:10–4.CrossRefPubMed

20.

Stack J, Doyle SL, Connolly DJ, Reinert LS, O’Keeffe KM, McLoughlin RM, et al. TRAM is required for TLR2 endosomal signaling to type I IFN induction. J Immunol. 2014;193:6090–102.CrossRefPubMedPubMedCentral

21.

Aubry C, Corr SC, Wienerroither S, Goulard C, Jones R, Jamieson AM, et al. Both TLR2 and TRIF contribute to interferon-beta production during Listeria infection. PLoS ONE. 2012;7:e33299.CrossRefPubMedPubMedCentral

22.

Dietrich N, Lienenklaus S, Weiss S, Gekara NO. Murine toll-like receptor 2 activation induces type I interferon responses from endolysosomal compartments. PLoS ONE. 2010;5:e10250.CrossRefPubMedPubMedCentral

23.

Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem. 1982;126:131–8.CrossRefPubMed

24.

Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11:373–84.CrossRefPubMed

25.

Toshchakov V, Jones BW, Lentschat A, Silva A, Perera PY, Thomas K, et al. TLR2 and TLR4 agonists stimulate unique repertoires of host resistance genes in murine macrophages: interferon-beta-dependent signaling in TLR4-mediated responses. J Endotoxin Res. 2003;9:169–75.CrossRefPubMed

26.

Barbalat R, Lau L, Locksley RM, Barton GM. Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands. Nat Immunol. 2009;10:1200–7.CrossRefPubMedPubMedCentral

27.

Li J, Lee DS, Madrenas J. Evolving bacterial envelopes and plasticity of TLR2-dependent responses: basic research and translational opportunities. Front Immunol. 2013;4:347.PubMedPubMedCentral

28.

Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014;5:461.CrossRefPubMedPubMedCentral

29.

Yu T, Yi YS, Yang Y, Oh J, Jeong D, Cho JY. The pivotal role of TBK1 in inflammatory responses mediated by macrophages. Mediators Inflamm. 2012;2012:979105.CrossRefPubMedPubMedCentral

Titel: Pam2CSK4 and Pam3CSK4 induce iNOS expression via TBK1 and MyD88 molecules in mouse macrophage cell line RAW264.7
verfasst von: Panthong Kulsantiwong
Matsayapan Pudla
Chanya Srisaowakarn
Jitrada Boondit
Pongsak Utaisincharoen
Publikationsdatum: 07.06.2017
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 10/2017
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-017-1063-1

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