Expression Analysis of the Human Caspase-1 Subfamily Reveals Specific Regulation of the CASP5 Gene by Lipopolysaccharide and Interferon-γ

Based on high sequence homology, there are six members in the caspase-1 subfamily: caspases 1, 4, 5, and 13 in humans and caspases 1, 11, and 12 in mice. Only caspase-1 is known to activate interleukin-1β and interleukin-18, and caspase-11 activates pro-caspase-1 in vivo. Almost nothing is known about caspases 4, 5, and 13. Here we report a sensitive and specific polymerase chain reaction system to analyze closely related genes. We employed this system to analyze the gene expression and regulation of human caspases 1, 4, 5, and 13, demonstrating that they have different expression patterns in normal tissues and cell lines. Interferon-γ strongly induced CASP1 and CASP5 but notCASP4 or CASP13 gene expression in HT-29 colon carcinoma cells. In contrast to the mRNA, interferon-γ up-regulated caspase-1 but not caspase-5 protein. In the monocytic cell line THP-1, CASP1 mRNA and caspase-1 protein are expressed constitutively, and their levels were not increased by lipopolysaccharide, whereas both CASP5 mRNA and caspase-5 protein were induced by lipopolysaccharide. Caspase-1 subfamily members displayed different in vitro activities toward pro-caspases 1 and 3 and pro-interleukin-1β. Our results demonstrate that caspase-1 and caspase-5 levels are modulated by interferon-γ and lipopolysaccharide, respectively, and suggest that caspase-1 subfamily members are differentially regulated and may have distinct functions. Based on high sequence homology, there are six members in the caspase-1 subfamily: caspases 1, 4, 5, and 13 in humans and caspases 1, 11, and 12 in mice. Only caspase-1 is known to activate interleukin-1β and interleukin-18, and caspase-11 activates pro-caspase-1 in vivo. Almost nothing is known about caspases 4, 5, and 13. Here we report a sensitive and specific polymerase chain reaction system to analyze closely related genes. We employed this system to analyze the gene expression and regulation of human caspases 1, 4, 5, and 13, demonstrating that they have different expression patterns in normal tissues and cell lines. Interferon-γ strongly induced CASP1 and CASP5 but notCASP4 or CASP13 gene expression in HT-29 colon carcinoma cells. In contrast to the mRNA, interferon-γ up-regulated caspase-1 but not caspase-5 protein. In the monocytic cell line THP-1, CASP1 mRNA and caspase-1 protein are expressed constitutively, and their levels were not increased by lipopolysaccharide, whereas both CASP5 mRNA and caspase-5 protein were induced by lipopolysaccharide. Caspase-1 subfamily members displayed different in vitro activities toward pro-caspases 1 and 3 and pro-interleukin-1β. Our results demonstrate that caspase-1 and caspase-5 levels are modulated by interferon-γ and lipopolysaccharide, respectively, and suggest that caspase-1 subfamily members are differentially regulated and may have distinct functions. interleukin lipopolysaccharide polymerase chain reaction interferon-γ cycloheximide glutathioneS-transferase reverse transcriptase-PCR glyceraldehyde-3-phosphate dehydrogenase 3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonic acid Caspases are a family of aspartic acid-specific proteases that fulfill varied and often critical roles in mammalian apoptosis or proteolytic activation of cytokines (1Thornberry N.A. Lazebnik Y. Science. 1998; 281: 1312-1316Crossref PubMed Scopus (6133) Google Scholar, 2Wolf B.B. Green D.R. J. Biol. Chem. 1999; 274: 20049-20052Abstract Full Text Full Text PDF PubMed Scopus (861) Google Scholar, 3Zheng T.S. Hunot S. Kuida K. Flavell R. Cell Death Differ. 1999; 6: 1043-1053Crossref PubMed Scopus (251) Google Scholar). Currently, 14 caspases have been discovered in mice and humans that represent at least 11 different enzymes (2Wolf B.B. Green D.R. J. Biol. Chem. 1999; 274: 20049-20052Abstract Full Text Full Text PDF PubMed Scopus (861) Google Scholar, 3Zheng T.S. Hunot S. Kuida K. Flavell R. Cell Death Differ. 1999; 6: 1043-1053Crossref PubMed Scopus (251) Google Scholar, 4Nicholson D.W. Cell Death Differ. 1999; 6: 1028-1042Crossref PubMed Scopus (1294) Google Scholar). Whereas caspases 1–3, 6–9, and 14 have homologues in mice and humans, caspases 4, 5, 10, and 13 have no known counterparts in mice; and conversely, caspases 11 and 12 have no known counterparts in humans (2Wolf B.B. Green D.R. J. Biol. Chem. 1999; 274: 20049-20052Abstract Full Text Full Text PDF PubMed Scopus (861) Google Scholar, 3Zheng T.S. Hunot S. Kuida K. Flavell R. Cell Death Differ. 1999; 6: 1043-1053Crossref PubMed Scopus (251) Google Scholar, 4Nicholson D.W. Cell Death Differ. 1999; 6: 1028-1042Crossref PubMed Scopus (1294) Google Scholar).Based on amino acid sequence homology and to a lesser extent the presence of a long N-terminal prodomain, caspases 1, 4, and 5 and caspases 11–13 constitute one distinct group: the caspase-1 subfamily (4Nicholson D.W. Cell Death Differ. 1999; 6: 1028-1042Crossref PubMed Scopus (1294) Google Scholar). The in vitro substrate preferences of caspases 1, 4, and 5 have been determined using small peptides, and they are very similar (5Garcia-Calvo M. Peterson E.P. Rasper D.M. Vaillancourt J.P. Zamboni R. Nicholson D.W. Thornberry N.A. Cell Death Differ. 1999; 6: 362-369Crossref PubMed Scopus (192) Google Scholar). Despite the fact that the caspase-1 subfamily is large and constitutes almost half the total number of known caspases, an appreciation of their regulation, functions, and activities is still inadequate. Caspase-1 is the best characterized and appears to be involved in some pathophysiological cell deaths (6Friedlander R.M. Yuan J. Cell Death Differ. 1998; 5: 823-831Crossref PubMed Scopus (95) Google Scholar). Importantly, it fulfills a major physiological role as an essential mediator of inflammation and immune regulation through the proteolytic processing and activation of IL-1β1 in macrophages and IL-18 (also called interferon-γ-inducing factor) in T cells (3Zheng T.S. Hunot S. Kuida K. Flavell R. Cell Death Differ. 1999; 6: 1043-1053Crossref PubMed Scopus (251) Google Scholar, 6Friedlander R.M. Yuan J. Cell Death Differ. 1998; 5: 823-831Crossref PubMed Scopus (95) Google Scholar, 7Fantuzzi G. Dinarello C.A. J. Clin. Immunol. 1999; 19: 1-11Crossref PubMed Scopus (420) Google Scholar).Murine caspase-11 is the only other partially characterized member of the caspase-1 subfamily. Mice deficient in caspase-11 have a very similar phenotype to Casp-1 −/− mice; for example, Casp-11 −/− mice are resistant to endotoxic shock induced by bacterial LPS and fail to produce mature interleukin-1α and IL-1β after LPS stimulation (8Wang S. Miura M. Jung Y.-K. Zhu H. Li E. Yuan J. Cell. 1998; 92: 501-509Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar). Moreover,Casp-11 −/− embryonic fibroblasts are resistant to apoptosis induced by ectopic expression of caspase-1, suggesting that caspase-11 is an upstream activator of caspase-1 (3Zheng T.S. Hunot S. Kuida K. Flavell R. Cell Death Differ. 1999; 6: 1043-1053Crossref PubMed Scopus (251) Google Scholar, 8Wang S. Miura M. Jung Y.-K. Zhu H. Li E. Yuan J. Cell. 1998; 92: 501-509Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar). Unlike caspase-1, the expression of caspase-11 is LPS-inducible (8Wang S. Miura M. Jung Y.-K. Zhu H. Li E. Yuan J. Cell. 1998; 92: 501-509Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar, 9Wang S. Miura M. Jung Y. Zhu H. Gagliardini V. Shi L. Greenberg Yuan J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google and it is to that other members of the family are regulated at the or by The human of caspase-11 is of the of about the and in of human proteases related to caspase-1, but it be or on sequence homology (4Nicholson D.W. Cell Death Differ. 1999; 6: 1028-1042Crossref PubMed Scopus (1294) Google we report the of a specific to and the gene expression and regulation of very closely related members of the caspase-1 subfamily. Our is very to be is using We that strongly expression of the and CASP5 but not the genes. Whereas gene but not the caspase-5 bacterial LPS both CASP5 mRNA and caspase-5 protein. the human CASP5 gene the gene in LPS We that the caspase-1 family members different in vitro activities toward is and but on a of the of the In this we that the only their the of by and LPS that we by is we the mRNA S. M. M. H. Cell Biol. Scholar, J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M. Kuida K. Flavell Cell. Biol. PubMed Scopus Google and the and IL-1β G. Dinarello C.A. J. Clin. Immunol. 1999; 19: 1-11Crossref PubMed Scopus (420) Google Scholar, 8Wang S. Miura M. Jung Y.-K. Zhu H. Li E. Yuan J. Cell. 1998; 92: 501-509Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar, 9Wang S. Miura M. Jung Y. Zhu H. Gagliardini V. Shi L. Greenberg Yuan J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google using this and have and sequence caspase-1, N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google Scholar, J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). Caspases 4, 5, and 13 are related to sequence the sequence caspases 4, 5, and 13 is at the N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google Scholar, J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). is to and mRNA the be that may very the other we for the of mRNA and that are the in the other 1, is the that the total of and the of for the expression of very closely related genes. this we have for the a of gene expression for the human caspase-1 subfamily in normal tissues and in or cell and sequence to caspase-1, and N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google Scholar, J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). is by and suggesting a role of in a J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). and Y. M. S. K. and G. whereas other caspases this family only and not In the whereas caspase-1 mature a of the may be distinct other members of the caspase-1 subfamily both on the of substrate and the fact that the expression of mRNA in human tissues and cell is by an on the sequence of the the cells. The expression of CASP13 mRNA and the of protein some in suggest that an role embryonic or that expression may be induced by a of human caspases and 5 are We that caspases 5 high 4, and 1 not the as caspase-1 and caspase-5 no on this Our results as substrate are very similar to using a different system H. J. 1998; PubMed Scopus Google Scholar). caspases and 5 induced apoptosis in cells N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. Y. J. PubMed Scopus Google Scholar, J. M. M. H. M. Li M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google there is no that they roles in as for example, caspases and (2Wolf B.B. Green D.R. J. Biol. Chem. 1999; 274: 20049-20052Abstract Full Text Full Text PDF PubMed Scopus (861) Google Scholar). it been that is apoptosis in cells S. M. H. Y. Y. PubMed Scopus Google Scholar). In of an of or of an suggesting that is involved S. M. H. Y. Y. PubMed Scopus Google Scholar). The protein sequence of is similar to caspase-11 S. Miura M. Jung Y. Zhu H. Gagliardini V. Shi L. Greenberg Yuan J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). is to be the human of the mRNA is high in tissues and is in contrast to the very levels of mice S. Miura M. Jung Y. Zhu H. Gagliardini V. Shi L. Greenberg Yuan J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Casp-11 mRNA is but mRNA is human CASP5 expression is very in normal and CASP5 expression be induced by bacterial a only We not by we an of a of very an or of a of the processing of caspase-5 after by very similar were in cells this suggest that increased expression of caspase-5 results in the fact that the preferences of caspases 5 and 11 toward are the of caspase-5 on a high caspase-5 a in that is in caspase-11 in other caspase-1 subfamily members N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. Y. J. PubMed Scopus Google Scholar, J. M. M. H. M. Li M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google Scholar, J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). were this in CASP5 in of the and S. H. M. M. J. M. 1999; Google Scholar). Based on caspase-5 is to be the human of activates pro-caspase-1 and is for the of In this we mRNA is strongly induced by a that roles in both and immune cell caspase-5 protein is not induced by suggesting that caspase-5 protein is The of results be the of Caspases are a family of aspartic acid-specific proteases that fulfill varied and often critical roles in mammalian apoptosis or proteolytic activation of cytokines (1Thornberry N.A. Lazebnik Y. Science. 1998; 281: 1312-1316Crossref PubMed Scopus (6133) Google Scholar, 2Wolf B.B. Green D.R. J. Biol. Chem. 1999; 274: 20049-20052Abstract Full Text Full Text PDF PubMed Scopus (861) Google Scholar, 3Zheng T.S. Hunot S. Kuida K. Flavell R. Cell Death Differ. 1999; 6: 1043-1053Crossref PubMed Scopus (251) Google Scholar). Currently, 14 caspases have been discovered in mice and humans that represent at least 11 different enzymes (2Wolf B.B. Green D.R. J. Biol. Chem. 1999; 274: 20049-20052Abstract Full Text Full Text PDF PubMed Scopus (861) Google Scholar, 3Zheng T.S. Hunot S. Kuida K. Flavell R. Cell Death Differ. 1999; 6: 1043-1053Crossref PubMed Scopus (251) Google Scholar, 4Nicholson D.W. Cell Death Differ. 1999; 6: 1028-1042Crossref PubMed Scopus (1294) Google Scholar). Whereas caspases 1–3, 6–9, and 14 have homologues in mice and humans, caspases 4, 5, 10, and 13 have no known counterparts in mice; and conversely, caspases 11 and 12 have no known counterparts in humans (2Wolf B.B. Green D.R. J. Biol. Chem. 1999; 274: 20049-20052Abstract Full Text Full Text PDF PubMed Scopus (861) Google Scholar, 3Zheng T.S. Hunot S. Kuida K. Flavell R. Cell Death Differ. 1999; 6: 1043-1053Crossref PubMed Scopus (251) Google Scholar, 4Nicholson D.W. Cell Death Differ. 1999; 6: 1028-1042Crossref PubMed Scopus (1294) Google Scholar). Based on amino acid sequence homology and to a lesser extent the presence of a long N-terminal prodomain, caspases 1, 4, and 5 and caspases 11–13 constitute one distinct group: the caspase-1 subfamily (4Nicholson D.W. Cell Death Differ. 1999; 6: 1028-1042Crossref PubMed Scopus (1294) Google Scholar). The in vitro substrate preferences of caspases 1, 4, and 5 have been determined using small peptides, and they are very similar (5Garcia-Calvo M. Peterson E.P. Rasper D.M. Vaillancourt J.P. Zamboni R. Nicholson D.W. Thornberry N.A. Cell Death Differ. 1999; 6: 362-369Crossref PubMed Scopus (192) Google Scholar). Despite the fact that the caspase-1 subfamily is large and constitutes almost half the total number of known caspases, an appreciation of their regulation, functions, and activities is still inadequate. Caspase-1 is the best characterized and appears to be involved in some pathophysiological cell deaths (6Friedlander R.M. Yuan J. Cell Death Differ. 1998; 5: 823-831Crossref PubMed Scopus (95) Google Scholar). Importantly, it fulfills a major physiological role as an essential mediator of inflammation and immune regulation through the proteolytic processing and activation of IL-1β1 in macrophages and IL-18 (also called interferon-γ-inducing factor) in T cells (3Zheng T.S. Hunot S. Kuida K. Flavell R. Cell Death Differ. 1999; 6: 1043-1053Crossref PubMed Scopus (251) Google Scholar, 6Friedlander R.M. Yuan J. Cell Death Differ. 1998; 5: 823-831Crossref PubMed Scopus (95) Google Scholar, 7Fantuzzi G. Dinarello C.A. J. Clin. Immunol. 1999; 19: 1-11Crossref PubMed Scopus (420) Google Scholar). caspase-11 is the only other partially characterized member of the caspase-1 subfamily. Mice deficient in caspase-11 have a very similar phenotype to Casp-1 −/− mice; for example, Casp-11 −/− mice are resistant to endotoxic shock induced by bacterial LPS and fail to produce mature interleukin-1α and IL-1β after LPS stimulation (8Wang S. Miura M. Jung Y.-K. Zhu H. Li E. Yuan J. Cell. 1998; 92: 501-509Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar). Moreover,Casp-11 −/− embryonic fibroblasts are resistant to apoptosis induced by ectopic expression of caspase-1, suggesting that caspase-11 is an upstream activator of caspase-1 (3Zheng T.S. Hunot S. Kuida K. Flavell R. Cell Death Differ. 1999; 6: 1043-1053Crossref PubMed Scopus (251) Google Scholar, 8Wang S. Miura M. Jung Y.-K. Zhu H. Li E. Yuan J. Cell. 1998; 92: 501-509Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar). Unlike caspase-1, the expression of caspase-11 is LPS-inducible (8Wang S. Miura M. Jung Y.-K. Zhu H. Li E. Yuan J. Cell. 1998; 92: 501-509Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar, 9Wang S. Miura M. Jung Y. Zhu H. Gagliardini V. Shi L. Greenberg Yuan J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google and it is to that other members of the family are regulated at the or by The human of caspase-11 is of the of about the and in of human proteases related to caspase-1, but it be or on sequence homology (4Nicholson D.W. Cell Death Differ. 1999; 6: 1028-1042Crossref PubMed Scopus (1294) Google Scholar). Here we report the of a specific to and the gene expression and regulation of very closely related members of the caspase-1 subfamily. Our is very to be is using We that strongly expression of the and CASP5 but not the genes. Whereas gene but not the caspase-5 bacterial LPS both CASP5 mRNA and caspase-5 protein. the human CASP5 gene the gene in LPS We that the caspase-1 family members different in vitro activities toward is and but on a of the of the In this we that the only their the of by and LPS that we by is we the mRNA S. M. M. H. Cell Biol. Scholar, J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M. Kuida K. Flavell Cell. Biol. PubMed Scopus Google and the and IL-1β G. Dinarello C.A. J. Clin. Immunol. 1999; 19: 1-11Crossref PubMed Scopus (420) Google Scholar, 8Wang S. Miura M. Jung Y.-K. Zhu H. Li E. Yuan J. Cell. 1998; 92: 501-509Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar, 9Wang S. Miura M. Jung Y. Zhu H. Gagliardini V. Shi L. Greenberg Yuan J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google using this and have and sequence caspase-1, N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google Scholar, J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). Caspases 4, 5, and 13 are related to sequence the sequence caspases 4, 5, and 13 is at the N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google Scholar, J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). is to and mRNA the be that may very the other we for the of mRNA and that are the in the other 1, is the that the total of and the of for the expression of very closely related genes. this we have for the a of gene expression for the human caspase-1 subfamily in normal tissues and in or cell and sequence to caspase-1, and N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google Scholar, J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). is by and suggesting a role of in a J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). and Y. M. S. K. and G. whereas other caspases this family only and not In the whereas caspase-1 mature a of the may be distinct other members of the caspase-1 subfamily both on the of substrate and the fact that the expression of mRNA in human tissues and cell is by an on the sequence of the the cells. The expression of CASP13 mRNA and the of protein some in suggest that an role embryonic or that expression may be induced by a of human caspases and 5 are We that caspases 5 high 4, and 1 not the as caspase-1 and caspase-5 no on this Our results as substrate are very similar to using a different system H. J. 1998; PubMed Scopus Google Scholar). caspases and 5 induced apoptosis in cells N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. Y. J. PubMed Scopus Google Scholar, J. M. M. H. M. Li M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google there is no that they roles in as for example, caspases and (2Wolf B.B. Green D.R. J. Biol. Chem. 1999; 274: 20049-20052Abstract Full Text Full Text PDF PubMed Scopus (861) Google Scholar). it been that is apoptosis in cells S. M. H. Y. Y. PubMed Scopus Google Scholar). In of an of or of an suggesting that is involved S. M. H. Y. Y. PubMed Scopus Google Scholar). The protein sequence of is similar to caspase-11 S. Miura M. Jung Y. Zhu H. Gagliardini V. Shi L. Greenberg Yuan J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). is to be the human of the mRNA is high in tissues and is in contrast to the very levels of mice S. Miura M. Jung Y. Zhu H. Gagliardini V. Shi L. Greenberg Yuan J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Casp-11 mRNA is but mRNA is human CASP5 expression is very in normal and CASP5 expression be induced by bacterial a only We not by we an of a of very an or of a of the processing of caspase-5 after by very similar were in cells this suggest that increased expression of caspase-5 results in the fact that the preferences of caspases 5 and 11 toward are the of caspase-5 on a high caspase-5 a in that is in caspase-11 in other caspase-1 subfamily members N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. Y. J. PubMed Scopus Google Scholar, J. M. M. H. M. Li M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google Scholar, J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). were this in CASP5 in of the and S. H. M. M. J. M. 1999; Google Scholar). Based on caspase-5 is to be the human of activates pro-caspase-1 and is for the of In this we mRNA is strongly induced by a that roles in both and immune cell caspase-5 protein is not induced by suggesting that caspase-5 protein is The of results be the of is and but on a of the of the In this we that the only their the of by and LPS that we by is we the mRNA S. M. M. H. Cell Biol. Scholar, J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M. Kuida K. Flavell Cell. Biol. PubMed Scopus Google and the and IL-1β G. Dinarello C.A. J. Clin. Immunol. 1999; 19: 1-11Crossref PubMed Scopus (420) Google Scholar, 8Wang S. Miura M. Jung Y.-K. Zhu H. Li E. Yuan J. Cell. 1998; 92: 501-509Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar, 9Wang S. Miura M. Jung Y. Zhu H. Gagliardini V. Shi L. Greenberg Yuan J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google using this and have and sequence caspase-1, N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google Scholar, J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). Caspases 4, 5, and 13 are related to sequence the sequence caspases 4, 5, and 13 is at the N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google Scholar, J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). is to and mRNA the be that may very the other we for the of mRNA and that are the in the other 1, is the that the total of and the of for the expression of very closely related genes. this we have for the a of gene expression for the human caspase-1 subfamily in normal tissues and in or cell lines. and sequence to caspase-1, and N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google Scholar, J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). is by and suggesting a role of in a J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). and Y. M. S. K. and G. whereas other caspases this family only and not In the whereas caspase-1 mature a of the may be distinct other members of the caspase-1 subfamily both on the of substrate and the fact that the expression of mRNA in human tissues and cell is by an on the sequence of the the cells. The expression of CASP13 mRNA and the of protein some in suggest that an role embryonic or that expression may be induced by a The of human caspases and 5 are We that caspases 5 high 4, and 1 not the as caspase-1 and caspase-5 no on this Our results as substrate are very similar to using a different system H. J. 1998; PubMed Scopus Google Scholar). caspases and 5 induced apoptosis in cells N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. Y. J. PubMed Scopus Google Scholar, J. M. M. H. M. Li M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google there is no that they roles in as for example, caspases and (2Wolf B.B. Green D.R. J. Biol. Chem. 1999; 274: 20049-20052Abstract Full Text Full Text PDF PubMed Scopus (861) Google Scholar). it been that is apoptosis in cells S. M. H. Y. Y. PubMed Scopus Google Scholar). In of an of or of an suggesting that is involved S. M. H. Y. Y. PubMed Scopus Google Scholar). The protein sequence of is similar to caspase-11 S. Miura M. Jung Y. Zhu H. Gagliardini V. Shi L. Greenberg Yuan J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). is to be the human of the mRNA is high in tissues and is in contrast to the very levels of mice S. Miura M. Jung Y. Zhu H. Gagliardini V. Shi L. Greenberg Yuan J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Casp-11 mRNA is but mRNA is human CASP5 expression is very in normal and CASP5 expression be induced by bacterial a only We not by we an of a of very an or of a of the processing of caspase-5 after by very similar were in cells this suggest that increased expression of caspase-5 results in the fact that the preferences of caspases 5 and 11 toward are the of caspase-5 on a high caspase-5 a in that is in caspase-11 in other caspase-1 subfamily members N.A. Vaillancourt J.P. Nicholson D.W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. Y. J. PubMed Scopus Google Scholar, J. M. M. H. M. Li M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. PubMed Scopus Google Scholar, J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). were this in CASP5 in of the and S. H. M. M. J. M. 1999; Google Scholar). Based on caspase-5 is to be the human of activates pro-caspase-1 and is for the of In this we mRNA is strongly induced by a that roles in both and immune cell caspase-5 protein is not induced by suggesting that caspase-5 protein is The of results be the of We are to Yuan for caspase-11 V. for CASP13 for for and for We Li and for the