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Written | My best friend, old Red Riding Hood editor | xi The innate immune system can sense external danger signals (damage-associated molecular patterns, referred to as DAMP) to activate inflammasomes.
Activated inflammasomes can release caspase-1 and caspase-11.
While cutting the precursor of IL-1β into mature IL-1β, it can also cleave a type of perforating protein called Gasdermin D, thereby forming the cell membrane.
Small holes cause cell pyrolysis [1,2].
When germs invade, the body can initiate this inflammatory response by recognizing the LPS signal of lipopolysaccharide.
Of course, if this reaction is over-activated, it will damage tissues and organs, cause sepsis, and endanger life [3-6].
However, how LPS causes sepsis is still unknown.
On January 4, 2021, the Vijay A Rathinam research group from the University of Connecticut published an article titled Intracellular immune sensing promotes inflammation via gasdermin D–driven release of a lectin alarmin in the journal Nature Immunology.
Through the method of proteomics, we found that LPS can promote the release of a lectin called Galectin-1, thereby initiating an inflammatory response.
It has been reported that after cells are stimulated by LPS, they can induce the secretion of IL-1β, the occurrence of pyrolysis, and the release of some DAMP [5].
However, the type and mechanism of releasing DAMP are still unknown.
In order to study this problem, the author took the bone marrow-derived macrophages of wild-type and caspase-11-deficient mice as the research object, and took the caspase-11 specific activator Escherichia coli as the stimulant to release the components outside the cell.
Perform proteomics research and determination.
The authors found that, compared with the supernatant of caspase-11-deficient mouse macrophages, wild-type mice specifically secrete Galectin-1.
Galectin-1 is a type of lectin that can be combined with β-galactoside, and its secretion mechanism is still unknown [7,8].
Next, the authors used knockout mice of each component of the inflammasome to study the determinants of Galectin-1 release.
The authors found that for Gasdermin D knockout mice, the level of Galectin-1 released by bone marrow-derived macrophages was significantly reduced under the stimulation of E.
coli compared with other wild-type and gene knockout mice.
This shows that the secretion of Galectin-1 depends on the Gasdermin D-caspase-11 signaling pathway, rather than the traditional NLRP3-caspase-1 inflammasome signaling pathway.
In order to study whether the above conclusions are also universal in mice, the author injected lipopolysaccharides into mice, and measured the level of Galectin-1 in the cytoplasm and abdominal cavity in real time.
The authors found that the secretion level of Galectin-1 was different from the concentration of lipopolysaccharide injected.
Shows a positive correlation, and it rises with time.
Not surprisingly, this phenomenon was not found in GasderminD knockout mice.
Sepsis is a type of disease with a high fatality rate.
In order to study its relationship with the release of Galectin-1, the author used the serum of patients suffering from sepsis as the research object.
Compared with patients with sepsis, the level of Galectin-1 in the serum of patients with sepsis was significantly higher.
This shows that in the course of sepsis, Galectin-1 will be released into the circulatory system.
In order to further study the biological significance of Galectin-1, the authors used Galectin-1-deficient mice as the research object.
Through the lipopolysaccharide-induced sepsis model, they found that compared with wild-type mice, Galectin-1-deficient mice have Survival rate is significantly improved, and organ damage is also significantly improved.
Of course, caspase-11 and Gasdermin D-deficient mice also have this phenomenon.
At the same time, injecting Galectin-1 neutralizing antibody into wild-type mice can also play a protective role.
Finally, the authors study the specific role of Galectin-1 in systemic inflammation.
The author injected lipopolysaccharide into wild-type and Galectin-1 knockout mice, and detected and analyzed the expression levels of inflammatory factors and chemokines in their cytoplasm.
The authors found that compared with wild-type mice, in Galectin-1-deficient mice, IL-3, IL-6, TNF, interferon-γ, GCSF (granulocyte-colony stimulating factor), GMCSF (granulocyte-macrophage colony- stimulating factor), IL-1α, IL-1β and IL-12 and other pro-inflammatory factors decreased significantly, and the levels of MCP-1, MIP-1α, MIP-1β and other chemokines also decreased.
In order to further study this problem, the authors extracted the spleen and lungs of mice and performed RNA sequencing, and found that the inflammation-related and immune response-related pathways of galectin-1-deficient mice were weakened and down-regulated.
These results all indicate that Galectin-1 can promote the inflammatory response induced by lipopolysaccharide, and this inflammatory state is likely to be one of the causes of sepsis.
In summary, the author found that lipopolysaccharide can induce the secretion and release of a lectin called Galectin-1 through proteomics methods.
Through Galectin-1-deficient mice and neutralizing antibodies, the authors confirmed that Galectin-1 can promote and enhance inflammation levels and play a key role in the lipopolysaccharide-induced sepsis model.
Original link https://doi.
org/10.
1038/s41590-020-00844-7 Plate maker: Qijiang, swipe up to read references [1] Kayagaki, N.
et al.
Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling.
Nature 526, 666–671 (2015).
[2] Shi, J.
et al.
Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death.
Nature 526, 660–665 (2015).
[3] Cheng, KT et al.
Caspase-11-mediated endothelial pyroptosis underlies endotoxemia-induced lung injury.
J.
Clin.
Invest.
127, 4124–4135 (2017).
[4] Kang, R.
et al.
Lipid peroxidation drives gasdermin D-mediated pyroptosis in lethal polymicrobial sepsis.
Cell Host Microbe 24, 97–108.
e4 (2018).
[5] Kayagaki, N.
et al.
Non-canonical inflammasome activation targets caspase-11.
Nature 479, 117–121 (2011).
[6 】 Song, F.
et al.
Sphingosine-1-phosphate receptor 2 signaling promotes caspase-11–dependent macrophage pyroptosis and worsens Escherichia coli sepsis outcome.
Anesthesiology 129, 311–320 (2018).
[7] Sundblad, V.
, Morosi, LG, Geffner, JR & Rabinovich , GA Galectin-1: a jack-of-all-trades in the resolution of acute and chronic inflammation.
J.
Immunol.
199, 3721–3730 (2017).
【8】Camby, I.
, Le Mercier, M.
, Lefranc, F.
& Kiss, R.
Galectin-1: a small protein with major functions.
Glycobiology 16, 137R–157R (2006).
a small protein with major functions.
Glycobiology 16, 137R–157R (2006).
a small protein with major functions.
Glycobiology 16, 137R–157R (2006).
Activated inflammasomes can release caspase-1 and caspase-11.
While cutting the precursor of IL-1β into mature IL-1β, it can also cleave a type of perforating protein called Gasdermin D, thereby forming the cell membrane.
Small holes cause cell pyrolysis [1,2].
When germs invade, the body can initiate this inflammatory response by recognizing the LPS signal of lipopolysaccharide.
Of course, if this reaction is over-activated, it will damage tissues and organs, cause sepsis, and endanger life [3-6].
However, how LPS causes sepsis is still unknown.
On January 4, 2021, the Vijay A Rathinam research group from the University of Connecticut published an article titled Intracellular immune sensing promotes inflammation via gasdermin D–driven release of a lectin alarmin in the journal Nature Immunology.
Through the method of proteomics, we found that LPS can promote the release of a lectin called Galectin-1, thereby initiating an inflammatory response.
It has been reported that after cells are stimulated by LPS, they can induce the secretion of IL-1β, the occurrence of pyrolysis, and the release of some DAMP [5].
However, the type and mechanism of releasing DAMP are still unknown.
In order to study this problem, the author took the bone marrow-derived macrophages of wild-type and caspase-11-deficient mice as the research object, and took the caspase-11 specific activator Escherichia coli as the stimulant to release the components outside the cell.
Perform proteomics research and determination.
The authors found that, compared with the supernatant of caspase-11-deficient mouse macrophages, wild-type mice specifically secrete Galectin-1.
Galectin-1 is a type of lectin that can be combined with β-galactoside, and its secretion mechanism is still unknown [7,8].
Next, the authors used knockout mice of each component of the inflammasome to study the determinants of Galectin-1 release.
The authors found that for Gasdermin D knockout mice, the level of Galectin-1 released by bone marrow-derived macrophages was significantly reduced under the stimulation of E.
coli compared with other wild-type and gene knockout mice.
This shows that the secretion of Galectin-1 depends on the Gasdermin D-caspase-11 signaling pathway, rather than the traditional NLRP3-caspase-1 inflammasome signaling pathway.
In order to study whether the above conclusions are also universal in mice, the author injected lipopolysaccharides into mice, and measured the level of Galectin-1 in the cytoplasm and abdominal cavity in real time.
The authors found that the secretion level of Galectin-1 was different from the concentration of lipopolysaccharide injected.
Shows a positive correlation, and it rises with time.
Not surprisingly, this phenomenon was not found in GasderminD knockout mice.
Sepsis is a type of disease with a high fatality rate.
In order to study its relationship with the release of Galectin-1, the author used the serum of patients suffering from sepsis as the research object.
Compared with patients with sepsis, the level of Galectin-1 in the serum of patients with sepsis was significantly higher.
This shows that in the course of sepsis, Galectin-1 will be released into the circulatory system.
In order to further study the biological significance of Galectin-1, the authors used Galectin-1-deficient mice as the research object.
Through the lipopolysaccharide-induced sepsis model, they found that compared with wild-type mice, Galectin-1-deficient mice have Survival rate is significantly improved, and organ damage is also significantly improved.
Of course, caspase-11 and Gasdermin D-deficient mice also have this phenomenon.
At the same time, injecting Galectin-1 neutralizing antibody into wild-type mice can also play a protective role.
Finally, the authors study the specific role of Galectin-1 in systemic inflammation.
The author injected lipopolysaccharide into wild-type and Galectin-1 knockout mice, and detected and analyzed the expression levels of inflammatory factors and chemokines in their cytoplasm.
The authors found that compared with wild-type mice, in Galectin-1-deficient mice, IL-3, IL-6, TNF, interferon-γ, GCSF (granulocyte-colony stimulating factor), GMCSF (granulocyte-macrophage colony- stimulating factor), IL-1α, IL-1β and IL-12 and other pro-inflammatory factors decreased significantly, and the levels of MCP-1, MIP-1α, MIP-1β and other chemokines also decreased.
In order to further study this problem, the authors extracted the spleen and lungs of mice and performed RNA sequencing, and found that the inflammation-related and immune response-related pathways of galectin-1-deficient mice were weakened and down-regulated.
These results all indicate that Galectin-1 can promote the inflammatory response induced by lipopolysaccharide, and this inflammatory state is likely to be one of the causes of sepsis.
In summary, the author found that lipopolysaccharide can induce the secretion and release of a lectin called Galectin-1 through proteomics methods.
Through Galectin-1-deficient mice and neutralizing antibodies, the authors confirmed that Galectin-1 can promote and enhance inflammation levels and play a key role in the lipopolysaccharide-induced sepsis model.
Original link https://doi.
org/10.
1038/s41590-020-00844-7 Plate maker: Qijiang, swipe up to read references [1] Kayagaki, N.
et al.
Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling.
Nature 526, 666–671 (2015).
[2] Shi, J.
et al.
Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death.
Nature 526, 660–665 (2015).
[3] Cheng, KT et al.
Caspase-11-mediated endothelial pyroptosis underlies endotoxemia-induced lung injury.
J.
Clin.
Invest.
127, 4124–4135 (2017).
[4] Kang, R.
et al.
Lipid peroxidation drives gasdermin D-mediated pyroptosis in lethal polymicrobial sepsis.
Cell Host Microbe 24, 97–108.
e4 (2018).
[5] Kayagaki, N.
et al.
Non-canonical inflammasome activation targets caspase-11.
Nature 479, 117–121 (2011).
[6 】 Song, F.
et al.
Sphingosine-1-phosphate receptor 2 signaling promotes caspase-11–dependent macrophage pyroptosis and worsens Escherichia coli sepsis outcome.
Anesthesiology 129, 311–320 (2018).
[7] Sundblad, V.
, Morosi, LG, Geffner, JR & Rabinovich , GA Galectin-1: a jack-of-all-trades in the resolution of acute and chronic inflammation.
J.
Immunol.
199, 3721–3730 (2017).
【8】Camby, I.
, Le Mercier, M.
, Lefranc, F.
& Kiss, R.
Galectin-1: a small protein with major functions.
Glycobiology 16, 137R–157R (2006).
a small protein with major functions.
Glycobiology 16, 137R–157R (2006).
a small protein with major functions.
Glycobiology 16, 137R–157R (2006).
