ライフサイエンスコーパス: caspase 11

1 making them deficient in both caspase-1 and caspase-11.

2 cellular inflammasome complex that activates caspase-11.

3 re we demonstrate that this pathway requires caspase-11.

4 eover, LPS-mutant E. coli failed to activate caspase-11.

5 n NLRC4 and ASC, but not NLRP3, caspase-1 or caspase-11.

6 ence of an interferon-inducible activator of caspase-11.

7 gaging TRIF, Gram-negative bacteria activate caspase-11.

8 plying that there is a distinct activator of caspase-11.

9 ype I interferons were insufficient to prime caspase-11.

10 e-1, human caspase-4 and caspase-5, or mouse caspase-11.

11 However, humans do not encode caspase-11.

12 m mobilization, and potassium efflux but not caspase-11.

13 ) on the C57BL/6 J background that expressed caspase-11.

14 olates was independent of both caspase-1 and caspase-11.

15 spase-4, a potential human homolog of murine caspase-11.

16 TRIF regulated expression of caspase-11, a caspase-1-related protease that is critica

17 Caspase-11, a member of the murine caspase family, has b

18 al inflammasome was described that activates caspase-11, a pro-inflammatory caspase required for lipo

19 lammasome pathway that ultimately results in caspase-11 activation and cell death.

20 polysaccharide (LPS) in the cytosol triggers caspase-11 activation and is central to host defense aga

21 chia coli has recently been shown to trigger caspase-11 activation and pyroptosis, but the cytoplasmi

22 g fraction of immortalized macrophages after caspase-11 activation by lipopolysaccharide.

23 e or absence of RIP3 inhibited caspase-1 and caspase-11 activation by Nlrp3 stimuli but not the Nlrc4

24 During endotoxemia, however, excessive caspase-11 activation causes shock.

25 Here we show that non-canonical caspase-11 activation contributes to macrophage death du

26 he cytosolic entry of LPS and, consequently, caspase-11 activation during Gram-negative bacterial inf

27 nt interferon-beta production is crucial for caspase-11 activation in macrophages, but is only partia

28 sion of IcaA in L. pneumophila inhibited the caspase-11 activation in macrophages.

29 saccharide (LPS) is the signal that triggers caspase-11 activation in mice.

30 ng a divergent lipid A structure antagonized caspase-11 activation in response to E. coli LPS or Gram

31 ulated the host components required for this caspase-11 activation pathway.

32 Activation by Legionella differed from caspase-11 activation using previously described agonist

33 iously described agonists in that Legionella caspase-11 activation was rapid and required bacteria wi

34 microbial infection and trigger caspase-1 or caspase-11 activation, culminating in cytokine secretion

35 ssion, and cytosolic LPS directly stimulates caspase-11 activation, promoting the release of proinfla

36 ophagosomes, which results in a reduction of caspase-11 activation.

37 ion, however, in vitro studies indicate that caspase-11 acts upstream of NLRP3 and caspase-1.

38 expression of IL1-beta, TNF-alpha, HSP70 and Caspase 11 all increased over control levels found in un

39 with C57BL/6 Casp11 gene-targeted mice, that caspase-11 (also known as caspase-4) is critical for cas

40 depletion of caspase-4, a human ortholog of caspase-11, also led to increased bacterial colonization

41 daptive immune responses and are elicited by caspase-11, an enzyme that binds oxPAPC and bacterial li

42 /- and p53+/- mice showed virtual absence of caspase 11 and marked attenuation of caspases 1 and 12,

43 identify gasdermin D as a critical target of caspase-11 and a key mediator of the host response again

44 tly, the published Casp1(-/-) mice lack both caspase-11 and caspase-1.

45 eling proteins, interacts and regulates both caspase-11 and caspase-1.

46 In this study, we investigated a role for caspase-11 and caspase-12 in obesity and insulin resista

47 gand binding proteins such as the NAIPs, and caspase-11 and caspase-8 in addition to caspase-1.

48 ivation indicated by decreased activation of caspase-11 and decreased IL-1beta, compared with other g

49 nduced sepsis in StB KO mice is dependent on caspase-11 and mitochondrial reactive oxygen species but

50 ributed to the activation of the LPS-sensing caspase-11 and NLRP3 inflammasome by Gram-negative bacte

51 1-activated IL-18 induces IFN-gamma to prime caspase-11 and rapidly clear B. thailandensis infection.

52 ts included, besides Nalp1b, proinflammatory caspase-11 and the caspase-1 substrate alpha-enolase.

53 annexin-1 required the catalytic activity of caspase-11 and was essential for ATP release and P2X7-me

54 ammasome components, activates caspase-1 and caspase-11, and induces host-cell death and secretion of

55 apping and unique functions of caspase-1 and caspase-11 are difficult to unravel without additional g

56 Caspase-1 and caspase-11 are proinflammatory caspases that regulate cy

57 The enzymatic activities of caspase-1 and caspase-11 are required for growth inhibition in differe

58 procaspase involved in inflammation (murine caspase-11) are also activated by oligomerization.

59 Inflammatory caspases, including caspase-11, are upregulated in CD8(+) T cells after Ag-s

60 in 1) inflammasome] consisting of caspase-1, caspase-11, ASC (apoptosis-associated speck-like protein

61 spase-1 provides priming signals upstream of caspase-11 but not caspase-4 during murine defense again

62 Second, either caspase-1 or caspase-11 can trigger a form of lytic, programmed cell

63 Caspase-11 (Cas11) is a cysteine protease involved in pr

64 ackgrounds including Il1b/Il18-, caspase-1-, caspase-11- (Casp1/11-), and Tnf-deficient strains.

65 Furthermore, DCs from caspase-11 (casp11)-deficient 129S6 mice failed to secre

66 cognition and activation of pathways such as caspase-11 (caspase-4/5 in humans).

67 d Burkholderia thailandensis activates mouse caspase-11, causing pyroptotic cell death, interleukin-1

68 3-C3aR pathway in proinflammatory signaling, caspase-11 cell death, and sepsis severity.

69 By reconstituting caspase-1/caspase-11(-/-) cells with a noncleavable or catalytical

70 nsgenic for caspase-4, the human ortholog of caspase-11, cleared B. thailandensis in vivo, they did n

71 Purified active recombinant caspase-11 cleaves and activates procaspase-3 very effic

72 Mechanistically, caspase-11 cleaves gasdermin D, and the resulting amino-

73 further elucidating the mechanisms by which caspase-11 contributes to host defense.

74 Caspase-11 controls a noncanonical inflammasome that res

75 n caspase-4 and caspase-5, homologs of mouse caspase-11, cooperated to restrict L. pneumophila infect

76 We report that caspase-11-deficient (Casp11(-/-)) T cells proliferated

77 dition to its defect in cytokine maturation, caspase-11-deficient mice have a reduced number of apopt

78 colonization in the intestinal epithelium of caspase-11-deficient mice, but not at systemic sites.

79 Specifically, caspase-11-dependent cell death contributes to pathology

80 These results indicate that caspase-11-dependent cell death is detrimental to the ho

81 ide screen, we identified novel mediators of caspase-11-dependent cell death.

82 or caspase-11 gene expression and subsequent caspase-11-dependent cell death.

83 found that cytosolic LPS stimulation induced caspase-11-dependent cleavage of the pannexin-1 channel

84 hat delivers LPS into the cytosol triggering caspase-11-dependent effector responses in vitro and in

85 Intracellular LPS can then trigger caspase-11-dependent inflammasome activation in the cyto

86 Both lipids induce caspase-11-dependent interleukin-1 release, but only LPS

87 Here, we briefly review the burgeoning caspase-11-dependent non-canonical inflammasome field, f

88 induce GBP-dependent pyroptosis through both caspase-11-dependent noncanonical and caspase-1-dependen

89 re we show that gasdermin D is essential for caspase-11-dependent pyroptosis and interleukin-1beta ma

90 We found that the induction of caspase-11-dependent pyroptosis by cytoplasmic L. pneumo

91 I IFN receptor, there was a severe defect in caspase-11-dependent pyroptosis in these cells.

92 Caspase-11-dependent pyroptosis is triggered in IFN-acti

93 racellular lipopolysaccharide (LPS) leads to caspase-11-dependent pyroptosis, which is critical for i

94 Induction of caspase-11-dependent responses occurred in macrophages d

95 ate binding protein (Gbp) proteins stimulate caspase-11-dependent, cell-autonomous immunity in respon

96 We further demonstrated that caspase-1 and caspase-11 differentially contributed to the host defens

97 How caspase-11 executes these downstream signalling events i

98 In vivo, we observed increased caspase-11 expression and a significant decrease in the

99 n, and was mediated through the induction of caspase-11 expression and activation of caspase-3.

100 , these data suggest that IFN-gamma-mediated caspase-11 expression has a key role maintaining intesti

101 We find the Cpb1-C3-C3aR pathway induces caspase-11 expression through amplification of MAPK acti

102 polycytidylic acid [poly(I:C)] to induce pro-caspase-11 expression were as susceptible as wild-type m

103 rough TLR4 and interferon receptors, induces caspase-11 expression, and cytosolic LPS directly stimul

104 ages, but is only partially required for pro-caspase-11 expression, consistent with the existence of

105 -11(-/-) ) or sufficient (129 x C57BL/6) for caspase-11 expression, we found that caspase-11 was disp

106 mutation in the Casp11 locus that attenuated caspase-11 expression.

107 imally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF.

108 l role for pannexin-1 and P2X7 downstream of caspase-11 for pyroptosis and susceptibility to sepsis i

109 -)Casp11(129mt/129mt) macrophages expressing caspase-11 from a C57BL/6 bacterial artificial chromosom

110 ere, we review the emerging understanding of caspase-11 functions and the mechanisms of activation an

111 We further showed that increased caspase-11 gene expression and better pro-inflammatory c

112 rboxypeptidase B1 (Cpb1), to be required for caspase-11 gene expression and subsequent caspase-11-dep

113 nic mice were not altered by the ablation of caspase-11 gene.

114 and FOXF2, BMP-2, p75 neurotrophin receptor, caspase-11, guanylate-binding proteins 1 and 2, ApoJ/clu

115 ion, and insulin resistance, whereas loss of caspase-11 had no effect.

116 Most Gram-negative bacteria that activate caspase-11, however, are not cytosolic, and the mechanis

117 Recent studies indicate that caspase-8, caspase-11, IL-1R-associated kinases (IRAK), and recepto

118 We discuss the importance of caspase-1 and caspase-11 in host defense, and we examine the downstrea

119 flammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic G

120 ) and Case et al. (2013) identify a role for caspase-11 in rapid responses to bacterial pathogens tha

121 light on the lesser-studied proinflammatory caspase-11 in the combat between host and pathogens.

122 hich LPS from these bacteria gains access to caspase-11 in the cytosol remains elusive.

123 assessed the participation of caspase-1 and caspase-11 in the functions of the NLRC4 inflammasome an

124 highlight a unique pro-inflammatory role for caspase-11 in the innate immune response to clinically s

125 haride (LPS), or S. typhimurium LPS activate caspase-11 independently of the LPS receptor Toll-like r

126 Legionella activation of caspase-11 induced pyroptosis by a mechanism independent

127 IV secretion system and interferes with the caspase-11-induced, non-canonical activation of the infl

128 y, a noncanonical inflammasome controlled by caspase-11 induces cell death and IL-1 release.

129 Caspase-11 induces pyroptosis, a form of programmed cell

130 nt that is both necessary and sufficient for caspase-11 induction and autoactivation.

131 plasmic sensor for LPS and components of the caspase-11 inflammasome are not yet defined.

132 d for the full activity of the non-canonical caspase-11 inflammasome during infections with vacuolar

133 interleukin-1beta) through the non-canonical caspase-11 inflammasome.

134 nflammasome and did not affect non-canonical caspase-11, inflammasome activation.

135 Activation of caspase-1 and caspase-11 initiates pyroptotic host cell death that rel

136 Our data suggest that caspase-11 is a component of ICE complex and is required

137 Our results suggest that caspase-11 is a critical initiator caspase responsible f

138 Caspase-11 is a key regulator of caspase-1 and caspase-3

139 Thus, caspase-11 is critical for surviving exposure to ubiquit

140 to ATP and monosodium urate, indicating that caspase-11 is engaged by a non-canonical inflammasome.

141 Whether either ortholog functions similar to caspase-11 is poorly defined.

142 Here, we report that caspase-11 is required for innate immunity to cytosolic,

143 However, the signaling pathway downstream of caspase-11 is unknown.

144 We show here that the expression of caspase-11 is upregulated in the spinal cord of superoxi

145 iated inactivating passenger mutation on the caspase-11 locus, essentially making them deficient in b

146 utants of C. burnetii failed to suppress the caspase-11-mediated inflammasome activation induced by L

147 of macrophages with C. burnetii inhibits the caspase-11-mediated non-canonical activation of the NLRP

148 Caspase-11 mediates caspase-1 activation in response to

149 A second inflammatory caspase, mouse caspase-11, mediates pyroptotic death through an unknown

150 We find that caspase-11(-/-) mice display enhanced susceptibility to

151 These data indicate that caspase-11 negatively regulates TCR signaling, possibly

152 gered macrophage cell death, indicating that caspase-11 orchestrates both caspase-1-dependent and -in

153 e show C3aR is required for up-regulation of caspase-11 orthologues, caspase-4 and -5, in primary hum

154 Thus, although caspase-11 participates in flagellin-independent noncano

155 Priming the caspase-11 pathway in vivo resulted in extreme sensitivi

156 Priming the caspase-11 pathway in vivo with LPS or Toll-like recepto

157 Furthermore, we found that pro-caspase-11 physically interacts with pro-ICE in cells, a

158 anonical stimuli required NLRP3 and ASC, but caspase-11 processing and cell death did not, implying t

159 nt signaling pathway is required for in vivo caspase-11 production in intestinal epithelial cells dur

160 Caspase-11 promoted the fusion of the L. pneumophila vac

161 Lastly, loss of caspase-11 rather than caspase-1 protected mice from a l

162 Caspase-11 rather than caspase-1, however, was required

163 In addition, mouse caspase-11 (represented in humans by its orthologs, casp

164 For example, caspase-11 responds to LPS introduced into the cytosol a

165 Specifically, caspase-11 responds to penta- and hexa-acylated lipid A,

166 f the noncanonical inflammasome, mediated by caspase-11, serves as an additional pathway for the prod

167 e-11-/-;SOD1 G93A mice compared with that of caspase-11+/-; SOD1 G93A mice.

168 ly reduced in the spinal cord of symptomatic caspase-11-/-;SOD1 G93A mice compared with that of caspa

169 Legionella activation of caspase-11 stimulated activation of caspase-1 through NL

170 Caspase-11 subsequently synergizes with the assembled NL

171 Thus, TLR4- and TRIF-induced caspase-11 synthesis is critical for noncanonical Nlrp3

172 t mediate a capsase-11 response and that the caspase-11 system provides an alternative pathway for ra

173 estored fully by inhibition of Caspase-1 and Caspase-11, the murine homolog of Caspase-4.

174 These effects were mediated by caspase-11, TLR4, and complement, each of which trigger

175 t caspase-1 activity is required upstream of caspase-11 to control infection.

176 ASC in turn recruits caspase-1 and/or caspase-11 to form the AIM2 inflammasome.

177 Flightless-I targets caspase-11 to the Triton X-100-insoluble cytoskeleton fr

178 he individual contributions of caspase-1 and caspase-11 to this phenotype are not known.

179 The identification of TRIF as a regulator of caspase-11 underscores the importance of TLRs as master

180 in D (GSDMD) as a substrate of caspase-1 and caspase-11 upon detection of cytosolic lipopolysaccharid

181 oxPAPC and LPS bind caspase-11 via distinct domains and elicit different inf

182 TRIF activates caspase-11 via type I IFN signaling, an event that is bo

183 , we found that the optimal cleavage site of caspase-11 was (I/L/V/P)EHD, similar to that of upstream

184 Here, we demonstrated that caspase-11 was dispensable for caspase-1 activation in r

185 However, caspase-11 was dispensable for the fusion of lysosomes w

186 /6) for caspase-11 expression, we found that caspase-11 was dispensable for the restriction of Legion

187 Although caspase-11 was produced in macrophages deficient in the

188 e-11, we demonstrated that caspase-1 but not caspase-11 was required for pore formation, pyroptosis,

189 We also determined that active mouse caspase-11 was required for restriction of L. pneumophil

190 sing mice double deficient for caspase-1 and caspase-11, we assessed the participation of caspase-1 a

191 a and mice singly deficient for caspase-1 or caspase-11, we demonstrated that caspase-1 but not caspa

192 to identify new intracellular regulators of caspase-11, we found that Flightless-I, a member of the

193 as well as heat shock protein 70 (HSP70) and Caspase 11 were found to be increased up to 24 fold high

194 which includes murine Caspase 4 (also called Caspase 11), which we show is a direct p53 target gene.

195 These mutants triggered caspase-11, which enhanced clearance of S. typhimurium s

196 naturally invade the cytosol also triggered caspase-11, which protected mice from lethal challenge w

197 The observed increase in Caspase 11 with over-expression of miR-34a indicates tha

198 IP/NLRC4, NLRP6, and noncanonical caspase-4 (caspase-11) - within epithelial cells of the gut in muco