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1 he inhibition of secretary phospholipase A2 (sPLA2).
2 n/vesicle aggregation, as observed for hGIIA sPLA2.
3 xpression of group V sPLA2 but IIA not group sPLA2.
4 A2 and nonpancreatic human group IIA (hGIIA) sPLA2.
5 cles comparable to that of the human group V sPLA2.
6 the number of cells staining positively for sPLA2.
7 erably larger in hGX than in human group IIA sPLA2.
8 ade PIN showed positive immunoreactivity for sPLA2.
9 injury (MOF sPLA2, 2.4 +/- 0.97, vs. non-MOF sPLA2, 0.86 +/- 0.16 active units (AU); p < .05) and con
10 A2 activity beginning 36 hrs postinjury (MOF sPLA2, 2.4 +/- 0.97, vs. non-MOF sPLA2, 0.86 +/- 0.16 ac
12 enables further studies of the mechanisms of sPLA2 action influencing the development and tumorigenes
14 as no association of rs525380C>A with plasma sPLA2 activity (difference in geometric mean of sPLA2 ac
15 We tested the association of this SNP with sPLA2 activity and CHD events in 4 prospective and 14 ca
16 s show a strong association between elevated sPLA2 activity and CHD, no assay to measure sPLA2-V leve
17 he contribution of sPLA2-X to the measure of sPLA2 activity and coronary heart disease (CHD) risk tra
19 non-MOF patients, MOF patients had elevated sPLA2 activity beginning 36 hrs postinjury (MOF sPLA2, 2
20 able to distinguish differences in levels of sPLA2 activity between neoplasia-resistant strains, whic
21 nal ensemble averaging methods used to probe sPLA2 activity do not allow one to obtain such informati
23 ped a sensitive assay to directly quantitate sPLA2 activity in the murine intestinal tract utilizing
24 suppressed FLAG-pro-GX sPLA2 processing and sPLA2 activity in Y1 cells, and it significantly attenua
26 tissue was harvested for analysis of tissue sPLA2 activity or immediate use in an ex-vivo intestinal
28 A2 activity (difference in geometric mean of sPLA2 activity per rs525380 A-allele 0.4% (95% confidenc
30 C-Norfolk subjects in the highest tertile of sPLA2 activity were older and had higher inflammatory ma
31 variant, were significantly associated with sPLA2 activity, intermediate CHD risk traits, or CHD ris
32 h fluid (SIWF) was collected for analysis of sPLA2 activity, MUC2 density, and luminal levels of IL-4
34 dies report that secretory phospholipase A2 (sPLA2) activity is a marker for coronary heart disease (
36 ine if intestinal secreted phospholipase A2 (sPLA2) activity was also attenuated in susceptible strai
38 ted that group V secretory phospholipase A2 (sPLA2) amplifies the action of cytosolic phospholipase A
41 L-4 and IL-13 release and PN reduces luminal sPLA2 and MUC2, we hypothesized that adding IL-25 to PN
43 cation by two endogenous mechanisms, namely, sPLA2 and NHE1, which are known to be important for acid
44 : Agkistrodon piscivorus piscivorus (AppD49) sPLA2 and nonpancreatic human group IIA (hGIIA) sPLA2.
45 nd PGE2 , plasma secretory phospholipase A2 (sPLA2 ), and 11beta prostaglandin F2alpha (11betaPGF2alp
46 crobial molecule secretory phospholipase A2 (sPLA2) and the goblet cell glycoprotein mucin2 (MUC2).
47 ted with the human Group V secreted PLA2 (GV sPLA2) and the human Group VIA calcium-independent PLA2
48 de compound had appreciable inhibition of GV sPLA2, and none of the potent GIVA cPLA2 inhibitors inhi
49 the putative membrane binding surface of the sPLA2 are modestly more important for bactericidal activ
50 the first 5 d after birth, and inhibition of sPLA2 between days 0 to 1 and days 5 to 6 delays postnat
52 ase packing of DAPC and DMPE interferes with sPLA2 binding, irrespective of the phospholipid headgrou
56 he inflammatory-type human group IIA (hGIIA) sPLA2 circulates at high levels in the serum of malaria
57 f the products tested had elevated levels of sPLA2 compared with fresh plasma from healthy adult volu
61 as measured in vivo in wild-type (WT) and GX sPLA2-deficient (GX KO) mice and ex vivo using pancreati
62 Y1 cells, and it significantly attenuated GX sPLA2-dependent inhibition of steroidogenic acute regula
67 gher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increase
70 molecular weight secretory phospholipase A2 (sPLA2) enzymes in eicosanoid generation have relied on d
72 is study, using a FLAG epitope-tagged pro-GX sPLA2 expression construct (FLAG-pro-GX sPLA2), we deter
75 IN), and adenocarcinoma to determine whether sPLA2 expression is altered in the carcinogenesis of hum
76 onsistent with the contention that group IIA sPLA2 expression is elevated in neoplastic prostatic tis
78 ence of cPLA2 and secreted phospholipase A2 (sPLA2) Group IIA, Group V, and Group X on IL-8 and COX-2
79 ve previously showed the presence of Group V sPLA2 (GV sPLA2) in human and mouse atherosclerotic lesi
91 significantly attenuated infarction volume, sPLA2 IIA protein expression, PLA2 activity and signific
92 uggests that cytokine induction up-regulates sPLA2 IIA protein expression, resulting in altered lipid
93 egulation of secretory phospholipase A2 IIA (sPLA2 IIA) mRNA and protein expression, increased PLA2 a
95 tly increased PLA2 activity, secretory PLA2 (sPLA2)-IIA mRNA and protein levels, PtdCho-PLC activity,
97 ggest that both secretory PLA2 (sPLA2)-V and sPLA2-IIA (encoded, respectively, by the neighbouring PL
98 n a previous study, a selective inhibitor of sPLA2-IIA (LY315920NA/S-5920) was well tolerated and app
102 in vitro CN and CNJ culturing confirmed that sPLA2-IIa amplifies ocular surface inflammation in CNJ b
103 found in neutrophils only in the presence of sPLA2-IIA and 12-LO in an in vivo model of autoimmune in
104 mice, we show that the coordinated action of sPLA2-IIA and 12-LO promotes inflammatory arthritis.
107 3 and alpha4beta1 may serve as receptors for sPLA2-IIA and mediate pro-inflammatory action of sPLA2-I
108 er, the M-type receptor is species-specific: sPLA2-IIA binds to the M-type receptor in rodents and ra
111 sive GBS disease contain increased levels of sPLA2-IIA compared with normal sera from healthy individ
114 adenosine production (adsA strain) increased sPLA2-IIA expression in guinea pig airways and was clear
120 Continuous 7-day infusion of an inhibitor of sPLA2-IIA had no beneficial effect on 28-day all-cause m
124 nd the catalytically inactive H47Q mutant of sPLA2-IIA induced cell proliferation and ERK1/2 activati
128 atory action of sPLA2-IIA, and that integrin-sPLA2-IIA interaction is a novel therapeutic target.
133 6 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3
134 ) levels yet lower oxLDL/LDL (P = 0.006) and sPLA2-IIA mass (P = 0.04), probably reflecting LD with P
137 able analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and diff
139 t is entirely due to sPLA2-IIA, showing that sPLA2-IIA might represent an important component of humo
140 ment significantly attenuated PLA2 activity, sPLA2-IIA mRNA and protein levels, and PtdCho-PLC activi
141 enzyme activity in inbred strains containing sPLA2-IIA mutations; these strains were also associated
146 d for prostaglandin E2 production induced by sPLA2-IIa with various amount of sPLA2-IIa inhibitor, S-
147 hydrolysis of the mitochondrial membrane by sPLA2-IIA yields inflammatory mediators (ie, lysophospho
149 The type IIA secretory phospholipase A2 (sPLA2-IIA) is a host protein endowed with antibacterial
151 f human group IIA secreted phospholipase A2 (sPLA2-IIA), a bactericidal enzyme induced during acute i
152 substrate of secreted phospholipase A2 IIA (sPLA2-IIA), a phospholipase otherwise specific for bacte
153 d activity of secreted phospholipase A2 IIA (sPLA2-IIA), present in inflammatory fluids, and platelet
158 2-IIA and mediate pro-inflammatory action of sPLA2-IIA, and that integrin-sPLA2-IIA interaction is a
159 phase response in which serum amyloid A and sPLA2-IIa, present at sites of inflammation and tissue d
160 s Ptd-Cho levels by differentially affecting sPLA2-IIA, PtdCho-PLC, and CCTalpha after transient foca
161 t the bactericidal effect is entirely due to sPLA2-IIA, showing that sPLA2-IIA might represent an imp
162 Using transgenic mice that express human sPLA2-IIA, we demonstrate that this enzyme is crucial fo
165 ggest that, in the airway, S. aureus escapes sPLA2-IIA-mediated killing through adenosine-mediated in
169 r studies identified a unique function of gV-sPLA2 in activation of M and in their capacity to recrui
170 relative concentration variations of active sPLA2 in CSF and the specific enzymatic activity can be
171 Adoptive transfer studies suggested that gV-sPLA2 in dendritic cells was necessary for sensitization
172 provide clear evidence of a role for group V sPLA2 in regulating eicosanoid generation in response to
174 sly showed the presence of Group V sPLA2 (GV sPLA2) in human and mouse atherosclerotic lesions, its h
175 of detection (LOD) of human secretory PLA2 (sPLA2) in up to 1000-fold-diluted cerebrospinal fluid (C
177 A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely fo
180 chemically unrelated secretory phospholipase sPLA2 inhibitors, bromphenacylbromide and 1-hexadecyl-3-
181 on is replaced with a Z-olefin or an alkyne, sPLA2 inhibitory activity suffered relative to the natur
182 findings provide strong evidence that pro-GX sPLA2 is a substrate for furin and PCSK6 proteolytic pro
183 cells in the small intestine, while group X sPLA2 is expressed by Paneth/goblet-like cells in the co
189 that: 1) the overall positive charge of the sPLA2 is the dominant factor in dictating bactericidal p
196 These findings suggest that at least some sPLA2 isoforms must have significant roles in ocular sur
199 have identified a secreted phospholipase A2 (sPLA2)-like protein, BomoTx, from the Brazilian lancehea
200 ession levels of secretory phospholipase A2 (sPLA2), lysophospholipid acyltransferase (LPEAT), lysoph
202 IS was lower in MIN6 cells overexpressing GX sPLA2 (MIN6-GX) compared with control (MIN6-C) cells.
203 otein (LDL) particles, and the ability of GV sPLA2-modified LDL (GV-LDL) to induce macrophage foam ce
205 y 50% in peritoneal macrophages from group V sPLA2-null mice compared with macrophages from wild-type
207 hermore, peritoneal macrophages from group V sPLA2-null mice demonstrated a >50% attenuation in phago
212 he addition of IL-25 to PN increased luminal sPLA2 (P < 0.0001) and MUC2 (P < 0.02) compared with PN.
216 are formed by internalization of the Group V sPLA2 previously associated with the outer cellular surf
217 cotropic hormone (ACTH) enhanced FLAG-pro-GX sPLA2 processing and phospholipase activity secreted by
218 ketone significantly suppressed FLAG-pro-GX sPLA2 processing and sPLA2 activity in Y1 cells, and it
220 293 cells significantly enhanced FLAG-pro-GX sPLA2 processing, whereas siRNA-mediated knockdown of bo
222 matory response, secretory phospholipase A2 (sPLA2) reaches its maximum levels in plasma, where it is
225 ane association of two highly basic group II sPLA2's: Agkistrodon piscivorus piscivorus (AppD49) sPLA
226 cking group V secretory phospholipase A2 (gV-sPLA2) showed reduced eosinophilic pulmonary inflammatio
228 GX sPLA2 is produced as a pro-enzyme (pro-GX sPLA2) that contains an N-terminal 11-amino acid propept
229 for patient resuscitation was the source of sPLA2, the sPLA2 was measured in packed red blood cells,
230 oes not resemble that of the human group IIA sPLA2; the former is highly neutral, whereas the latter
232 er furin or PCSK6 enhanced the ability of GX sPLA2 to suppress liver X receptor reporter activity.
233 y was to characterize the plasma activity of sPLA2 type IIa in severely injured patients and to deter
234 a switch to a sequential induction of first sPLA2 (types IIa and V) that mediates the release of PAF
235 an studies suggest that both secretory PLA2 (sPLA2)-V and sPLA2-IIA (encoded, respectively, by the ne
236 causally related, because cells deficient in sPLA2-V exhibited decreased phagocytosis, and cells over
240 investigate the hypothesized causal role of sPLA2-V in coronary heart disease (CHD) pathogenesis.
243 ls exists, and the only evidence linking the sPLA2-V isoform to atherosclerosis progression comes fro
244 sPLA2 activity and CHD, no assay to measure sPLA2-V levels exists, and the only evidence linking the
246 absence of an assay that directly quantifies sPLA2-V levels, we used PLA2G5 mRNA levels in a novel, m
251 at ethanolamine lysophospholipid (LPE) is an sPLA2-V-derived product that may be involved in regulati
254 t resuscitation was the source of sPLA2, the sPLA2 was measured in packed red blood cells, platelet c
258 o-GX sPLA2 expression construct (FLAG-pro-GX sPLA2), we determined that adrenocorticotropic hormone (
259 To further understand the role of group V sPLA2, we studied its localization in resting mouse peri
262 e immunohistochemical staining for group IIA sPLA2, whereas 63 of 69 total cases (91%) of high-grade
263 cytes is group X secretory phospholipase A2 (sPLA2), which liberates large amounts of AA and the lyso
264 of Crotalus atrox-secreted phospholipase A2 (sPLA2) with giant unilamellar vesicles (GUVs) composed o
266 ain lysophospholipid released in response to sPLA2-X activity, stimulates melanocyte dendricity.
267 al a relationship between epithelial-derived sPLA2-X and indirect AHR in asthma and that sPLA2-X serv
268 e treated human melanocytes with recombinant sPLA2-X and show that low levels of sPLA2-X stimulate bo
274 tion, our data suggest an important role for sPLA2-X in cutaneous pigmentation through the release of
281 during cellular activation, indicating that sPLA2-X is involved in activating the MAPK cascade leadi
282 ents with asthma and that epithelial-derived sPLA2-X may be increased in association with indirect AH
290 sPLA2-X and indirect AHR in asthma and that sPLA2-X serves as an epithelial regulator of inflammator
291 ombinant sPLA2-X and show that low levels of sPLA2-X stimulate both tyrosinase activity and melanocyt
293 sPLA2-X, to investigate the contribution of sPLA2-X to the measure of sPLA2 activity and coronary he
298 dy and complement were sensitive to lysis by sPLA2-X, suggesting a novel mechanism of antiviral surve
299 to use genetic variants of PLA2G10, encoding sPLA2-X, to investigate the contribution of sPLA2-X to t
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