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Does caspase-12 suppress inflammasome activation?

A Corrigendum to this article was published on 29 May 2013

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Figure 1: Canonical caspase-1 activation is not increased in reported caspase-12−/−S mice, and defective caspase-11 expression prevents non-canonical caspase-1 activation.
Figure 2: Caspase-12 deletion does not increase caspase-1-dependent cytokine secretion in BMDMs and in in vivo challenged caspase-12−/−V mice.

References

  1. Lamkanfi, M. & Dixit, V. M. Inflammasomes and their roles in health and disease. Annu. Rev. Cell Dev. Biol. 28, 137–161 (2012)

    Article  CAS  Google Scholar 

  2. Lamkanfi, M. & Dixit, V. M. Mechanisms and functions of inflammasomes. Cell 157, 1013–1022 (2014)

    Article  CAS  Google Scholar 

  3. Saleh, M. et al. Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. Nature 440, 1064–1068 (2006)

    Article  CAS  ADS  Google Scholar 

  4. Saleh, M. et al. Corrigendum: Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. Nature 508, 274 (2013)

    Article  ADS  Google Scholar 

  5. Stehlik, C. & Dorfleutner, A. COPs and POPs: modulators of inflammasome activity. J. Immunol. 179, 7993–7998 (2007)

    Article  CAS  Google Scholar 

  6. Kayagaki, N. et al. Non-canonical inflammasome activation targets caspase-11. Nature 479, 117–121 (2011)

    Article  CAS  ADS  Google Scholar 

  7. Deltagen, Inc. Casp12 summary of phenotypic analysis. (http://www.informatics.jax.org/external/ko/deltagen/713.html)

  8. Nakagawa, T. et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β. Nature 403, 98–103 (2000)

    Article  CAS  ADS  Google Scholar 

  9. Wu, J., Fernandes-Alnemri, T. & Alnemri, E. S. Involvement of the AIM2, NLRC4, and NLRP3 inflammasomes in caspase-1 activation by Listeria monocytogenes. J. Clin. Immunol. 30, 693–702 (2010)

    Article  CAS  Google Scholar 

  10. Litvak, V. et al. Function of C/EBPδ in a regulatory circuit that discriminates between transient and persistent TLR4-induced signals. Nature Immunol. 10, 437–443 (2009)

    Article  CAS  Google Scholar 

  11. Raza, S. et al. Analysis of the transcriptional networks underpinning the activation of murine macrophages by inflammatory mediators. J. Leukoc. Biol. 96, 167–183 (2014)

    Article  Google Scholar 

  12. Stowe, I., Lee, B. & Kayagaki, N. Caspase-11: arming the guards against bacterial infection. Immunol. Rev. 265, 75–84 (2015)

    Article  CAS  Google Scholar 

  13. Vande Walle, L. et al. Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis. Nature 512, 69–73 (2014)

    Article  ADS  Google Scholar 

Download references

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Correspondence to Mohamed Lamkanfi.

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Extended data figures and tables

Extended Data Figure 1 Description and genotyping of caspase-12−/−V mice.

a, Wild-type and caspase-12−/−S BMDMs were left untreated or treated with 0.5 μg ml1 LPS for 6 h. Expression of full-length caspase-11 or the truncated caspase-11 Δ110 transcript was determined by RT–PCR. b, Schematic representation of targeting strategy in caspase-12−/−V mice in C57BL/6 ES cells. c, Genotyping of caspase-12−/−V mice by PCR. d, Sequence analysis of genomic region encompassing exon 7 of the caspase-11 gene in caspase-12−/−V mice using the reverse primer described in ref. 6. e, Wild-type and caspase-12−/−V BMDMs were left untreated or treated with 0.5 μg ml1 LPS for 6 h. Expression of full-length caspase-11 transcript was determined by RT–PCR. f, Wild-type and caspase-12−/−v BMDMs were left untreated or treated with 0.5 μg ml1 LPS or 200 U ml1 IFN-γ for 24 h and lysates were immunoblotted for caspase-12, caspase-11, caspase-1 and β-actin. For uncropped gels, see Supplementary Fig. 3.

Extended Data Figure 2 Normal inflammasome signalling in caspase-12−/−G mice.

a, Wild-type and caspase-12−/−G BMDMs were left untreated or treated with 0.5 μg ml1 LPS. 24 h later, lysates were immunoblotted for caspase-12 and β-actin. be, Wild-type and caspase-12−/−G BMDMs were left untreated or primed with 0.5 μg ml1 LPS for 4 h and subsequently infected with C. rodentium (MOI = 25) for 18 h. Lysates were immunoblotted for caspase-1 (b) and supernatants were analysed for IL-1β (c), IL-18 (d) and LDH (e). fi, Wild-type and caspase-12−/−G BMDMs were left untreated or primed with 0.5 μg ml1 LPS for 3 h and then stimulated with 20 μM nigericin for 45 min. Lysates were immunoblotted for caspase-1 (f) and supernatants were analysed for IL-1β (g), IL-18 (h) and LDH (i). jm, Wild-type and caspase-12−/−G BMDMs were left untreated or infected with S. Typhimurium (MOI = 5) for 3 h. Lysates were immunoblotted for caspase-1 (j) and supernatants analysed for IL-1β (k), IL-18 (l) and LDH (m). Black arrows denote procaspase-1 and white arrows the p20 subunit. Data are representative of results from at least three experiments, and cytokine and LDH data are presented as mean ± s.d. from a single representative experiment, with each condition performed in triplicate. For uncropped gels, see Supplementary Fig. 3.

Extended Data Figure 3 Analysis of inflammasome signalling in splenocytes and caspase-12 expression in macrophages.

a, b, Splenocytes from wild-type and caspase-12−/−V mice were left untreated (Ctrl) or primed with 100 ng ml1 LPS (a) or 100 ng ml1 Pam3CSK4 (b). After 24 h, cells were stimulated with 5 mM ATP or 20 μM nigericin for 1 h. Supernatants were analysed for IL-6, IL-1β and IL-18. c, Wild-type and caspase-12−/−V BMDMs were treated with 0.5 μg ml1 LPS for the indicated times. Caspase-12 mRNA levels were determined by qRT–PCR. d, Analysis of published microarray data set from C57BL/6 BMDMs treated with 10 ng ml1 LPS11. e, Wild-type and caspase-12−/−V BMDMs were left untreated or treated with 0.5 μg ml1 LPS for the indicated times and lysates were immunoblotted for caspase-12 and caspase-11. f, g, Raw264.7, J774A.1 cells (f) and wild-type and caspase-12−/−V thioglycolate-elicited peritoneal macrophages (g) were left untreated or treated with 0.5 μg ml1 LPS for the indicated times and lysates were immunoblotted for caspase-12. The 24 h LPS-treated wild-type and caspase-12−/−V BMDMs were included as controls for specificity. h, Wild-type and caspase-12−/−V thioglycolate-elicited peritoneal macrophages were treated with 0.5 μg ml1 LPS for 6 h and caspase-12 mRNA levels were determined by qRT–PCR. All data are representative of at least 3 independent experiments, and cytokine and qRT–PCR data are presented as mean ± s.d. from a single representative experiment, with each condition performed in triplicate. For uncropped gels, see Supplementary Fig. 4.

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Vande Walle, L., Jiménez Fernández, D., Demon, D. et al. Does caspase-12 suppress inflammasome activation?. Nature 534, E1–E4 (2016). https://doi.org/10.1038/nature17649

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