Abstract：
:Sepsis is an etiologically complex and often fatal inflammatory process involving a multitude of cytokine signaling pathways. Tumor necrosis factor α (TNFα) acts as a central regulator of the acute-phase inflammatory response by recruiting immune cells, including circulating monocyte/macrophages, to sites of infection or tissue damage. Inorganic polyphosphate (polyP), a linear polymer of orthophosphate residues, has been found in almost all cells and tissues, but its functions in immunity remain largely unknown. In this study, we show that pre- or post-treatment of mice with polyP150 (average chain length of 150 phosphate residues) markedly increases survival from lipopolysaccharide (LPS)-induced shock and inhibits macrophage recruitment to the liver and lungs, resulting in protection against tissue injury. In accord with these in vivo results, pretreatment of cultured peritoneal macrophages with polyP150 inhibited chemotaxis and actin polarization in response to TNFα. PolyP150 also inhibited phosphorylation of stress-activated protein kinases c-Jun N-terminal kinase (JNK) and p38, two downstream signaling molecules of the TNFα cascade, thereby preventing cyclooxygenase-2 gene expression by macrophages. These findings suggest that polyP150 inhibits recruitment of macrophages into organs by regulating the TNFα-JNK/p38 pathway, which may, in turn, protect against multi-organ dysfunction and lethality induced by LPS. Our findings identify polyP regulation as a novel therapeutic target for sepsis.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Terashima-Hasegawa M,Ashino T,Kawazoe Y,Shiba T,Manabe A,Numazawa Sdoi
10.1016/j.bcp.2018.11.017subject
Has Abstractpub_date
2019-01-01 00:00:00pages
96-105eissn
0006-2952issn
1873-2968pii
S0006-2952(18)30495-7journal_volume
159pub_type
杂志文章abstract：:Administration of non-cholestatic doses of manganese (Mn2+) followed by injection of bilirubin (BR) results in a severe reduction in rat bile flow. Male Sprague-Dawley rats were given various doses of Mn2+ (2, 4.5, 8, and 18 mg/kg, i.v.) and killed 0.25, 1, 3, or 5 hr later. 54Mn2+ was used to evaluate Mn2+ content (m...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90435-6
更新日期：1985-11-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.bcp.2013.01.015
更新日期：2013-04-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.01.016
更新日期：2014-03-15 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2019-07-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90427-7
更新日期：1985-11-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90385-1
更新日期：1988-10-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.10.011
更新日期：2010-03-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90512-u
更新日期：1993-08-03 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)02130-2
更新日期：1996-02-09 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90338-1
更新日期：1984-06-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90419-x
更新日期：1989-06-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00205-6
更新日期：1998-11-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90543-e
更新日期：1991-02-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90403-r
更新日期：1991-12-11 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90021-n
更新日期：1993-05-25 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00659-x
更新日期：1998-05-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/0006-2952(91)90092-j
更新日期：1991-03-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90119-6
更新日期：1990-06-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90105-8
更新日期：1982-07-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90671-x
更新日期：1987-12-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01190-5
更新日期：2002-08-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90041-4
更新日期：1987-05-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90551-5
更新日期：1988-05-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90537-s
更新日期：1992-10-06 00:00:00
abstract：:During attempts to isolate and identify an endogenous ligand for the glycoside binding sites on Na+,K+-ATPase, bovine adrenal glands were found to contain a potent inhibitor of isolated Na+,K+-ATPase. The inhibitory principle was extracted from adrenal cortex, following homogenization in NaHCO3 solution and separation...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90537-4
更新日期：1985-07-15 00:00:00
abstract：:Purified ornithine decarboxylase (EC 4.1.1.17, ODC) transamidated with four putrescine moieties on four glutamine residues through the action of transglutaminase (EC 2.3.2.13, TGase) purified from guinea pig liver, when added to isolated rat liver nuclei, stoichiometrically increased the activity of RNA polymerase I (...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90614-1
更新日期：1982-11-01 00:00:00
abstract：:Intracellular GSH has some effects on protecting cells against cadmium and is involved in the development of resistance to cisplatin (CDDP). To determine the effects of intracellular GSH on expression of the heat shock genes (hsp) induced by cadmium in CDDP-resistant cancer cells, we used two human ovarian cancer cell...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00049-0
更新日期：1999-07-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90254-g
更新日期：1992-02-18 00:00:00
abstract：:LY83583 (6-anilino-5,8-quinolinedione), considered to be a relatively specific repressor of cyclic GMP formation, is shown in the present study to inhibit (K(i) = 3 microM) glutathione reductase from bovine intestinal mucosa. As glutathione disulphide has been reported to inhibit guanylate cyclase irreversibly [Braugh...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90236-p
更新日期：1993-06-22 00:00:00
abstract：:The mineralocorticoid receptor (MCR) from bovine kidney was purified on an affinity column containing covalently linked polyclonal IgG raised in the rabbit against rat kidney protein purified in the presence of RU 26752 that is specific to the MCR. The immuno-affinity eluate was excluded as a single peak during gel pe...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90153-8
更新日期：1994-09-15 00:00:00
