GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:18962899

From GONUTS
Jump to: navigation, search
Citation

Luo, L, Wang, Y, Feng, Q, Zhang, H, Xue, B, Shen, J, Ye, Y, Han, X, Ma, H, Xu, J, Chen, D and Yin, Z (2009) Recombinant protein glutathione S-transferases P1 attenuates inflammation in mice. Mol. Immunol. 46:848-57

Abstract

We have reported that intracellular glutathione S-transferases P1 (GSTP1) suppresses LPS (lipopolysaccharide)-induced excessive production of pro-inflammatory factors by inhibiting LPS-stimulated MAPKs (mitogen-activated protein kinases) as well as NF-kappaB activation. But under pathogenic circumstances, physiologic levels of GSTP1 are insufficient to stem pro-inflammatory signaling. Here we show that LPS-induced up-regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW246.7 cells is significantly reduced by incubating cells with recombinant GSTP1 protein. In vivo study demonstrates that treatment of mice (i.p.) with recombinant GSTP1 protein effectively suppresses the devastating effects of acute inflammation, which includes reduction of mortality rate of endotoxic shock, alleviation of LPS-induced acute lung injury and abrogation of thioglycolate (TG)-induced peritoneal deposition of leukocytes and polymorphonuclear cells (PMNs). Meanwhile, GSTP1 prevented LPS-induced TNF-alpha, IL-1beta, MCP-1 and NO production. Further investigation by using confocal microscopy and flow cytometry shows that recombinant GSTP1 protein can be delivered into RAW246.7 cells, mouse peritoneal macrophages and HEK 293 cells suggesting that extracellular GSTP1 protein could be transported across plasma membrane and act as a cytosolic protein. In conclusion our research demonstrates a new finding that increasing cellular GSTP1 level by supplement of recombinant GSTP1 effectively suppresses the devastating effects of acute inflammation.

Links

PubMed Online version:10.1016/j.molimm.2008.09.010

Keywords

Acute Lung Injury/chemically induced; Acute Lung Injury/drug therapy; Acute Lung Injury/immunology; Animals; Cell Line; Chemokine CCL2/immunology; Glutathione S-Transferase pi/immunology; Glutathione S-Transferase pi/pharmacology; Humans; Inflammation/diet therapy; Inflammation/immunology; Interleukin-1beta/immunology; Lipopolysaccharides/immunology; Lipopolysaccharides/toxicity; Mice; Mice, Inbred BALB C; NF-kappa B/immunology; Nitric Oxide/immunology; Nitric Oxide Synthase Type II/immunology; Protein Transport/drug effects; Protein Transport/immunology; Recombinant Proteins/immunology; Recombinant Proteins/pharmacology; Shock, Septic/chemically induced; Shock, Septic/drug therapy; Shock, Septic/immunology; Signal Transduction/drug effects; Signal Transduction/immunology; Tumor Necrosis Factor-alpha/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:GSTP1

involved_in

GO:0002674: negative regulation of acute inflammatory response

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GSTP1

involved_in

GO:0032720: negative regulation of tumor necrosis factor production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GSTP1

involved_in

GO:0032691: negative regulation of interleukin-1 beta production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GSTP1

involved_in

GO:0051771: negative regulation of nitric-oxide synthase biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GSTP1

involved_in

GO:2000469: negative regulation of peroxidase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GSTP1

involved_in

GO:2000429: negative regulation of neutrophil aggregation

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GSTP1

involved_in

GO:0071638: negative regulation of monocyte chemotactic protein-1 production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GSTP1

involved_in

GO:0043066: negative regulation of apoptotic process

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GSTP1

involved_in

GO:0002674: negative regulation of acute inflammatory response

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GSTP1

involved_in

GO:0009890: negative regulation of biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GSTP1

involved_in

GO:0032691: negative regulation of interleukin-1 beta production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GSTP1

involved_in

GO:0032720: negative regulation of tumor necrosis factor production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GSTP1

involved_in

GO:0043409: negative regulation of MAPK cascade

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GSTP1

involved_in

GO:0051771: negative regulation of nitric-oxide synthase biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GSTP1

involved_in

GO:0071638: negative regulation of monocyte chemotactic protein-1 production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.