p11, a Unique Member of the S100 Family of Calcium-binding Proteins, Interacts with and Inhibits the Activity of the 85-kDa Cytosolic Phospholipase A2

Abstract

Using a two hybrid system screen of a human cDNA library, we have found that p11, a unique member of the S100 family of calcium-binding proteins, interacts with the carboxyl region of the 85-kDa cytosolic phospholipase A2(cPLA2). p11 synthesized in a cell-free system interacts with cPLA2 in vitro. The p11-cPLA2complex is detectable from a human bronchial epithelial cell line (BEAS 2B). Furthermore, p11 inhibits cPLA2 activity in vitro. Selective inhibition of p11 expression in the BEAS 2B cells by antisense RNA results in an increased PLA2activity as well as an increased release of prelabeled arachidonic acid. This study demonstrates a novel mechanism for the regulation of cPLA2 by an S100 protein. Using a two hybrid system screen of a human cDNA library, we have found that p11, a unique member of the S100 family of calcium-binding proteins, interacts with the carboxyl region of the 85-kDa cytosolic phospholipase A2(cPLA2). p11 synthesized in a cell-free system interacts with cPLA2 in vitro. The p11-cPLA2complex is detectable from a human bronchial epithelial cell line (BEAS 2B). Furthermore, p11 inhibits cPLA2 activity in vitro. Selective inhibition of p11 expression in the BEAS 2B cells by antisense RNA results in an increased PLA2activity as well as an increased release of prelabeled arachidonic acid. This study demonstrates a novel mechanism for the regulation of cPLA2 by an S100 protein. Phospholipase A2s (PLA2, 1The abbreviations used are: PLA2, phospholipase A2; cPLA2, cytosolic phospholipase A2; AA, arachidonic acid; X-Gal, 5-bromo-4-chloro-3-indolyl-β-d-galactoside; bp, base pair; HPLC, high pressure liquid chromatography; PAGE, polyacrylamide gel electrophoresis; HBSS, Hanks' balanced salt solution. 1The abbreviations used are: PLA2, phospholipase A2; cPLA2, cytosolic phospholipase A2; AA, arachidonic acid; X-Gal, 5-bromo-4-chloro-3-indolyl-β-d-galactoside; bp, base pair; HPLC, high pressure liquid chromatography; PAGE, polyacrylamide gel electrophoresis; HBSS, Hanks' balanced salt solution. EC 3.1.1.4) are a group of enzymes that catalyze the hydrolysis of the sn-2-ester bond of phospholipids, resulting in the production of free fatty acid and lysophospholipids. These lipid products may serve as intracellular second messengers or can be further metabolized to potent inflammatory mediators. The release of arachidonic acid (AA) from membranes by PLA2 and its subsequent conversion into leukotrienes, prostaglandins, and other eicosanoids play a key role in the process leading to inflammation. Several mammalian PLA2s, including the 14-kDa secreted form PLA2 and the 85-kDa cytosolic PLA2 (cPLA2), have been proposed to mediate AA release and eicosanoid generation in various cell types (1Mayer R.J. Marshall L.A. FASEB J. 1993; 7: 339-348Crossref PubMed Scopus (444) Google Scholar, 2Mukherjee A.B. Miele L. Pattabiraman N. Biochem. Pharmacol. 1994; 48: 1-10Crossref PubMed Scopus (188) Google Scholar, 3Dennis E.A. J. Biol. Chem. 1994; 269: 13057-13060Abstract Full Text PDF PubMed Google Scholar). The mammalian low molecular mass 14-kDa PLA2s mainly include two types, type I and type II. Although the type I PLA2 is mainly found in pancreatic secretion, it has also been found in other mammalian tissues, and the physiological role of this extra-pancreatic type I PLA2 remains unclear. The type II PLA2 has been suggested to be involved in the pathogenesis of inflammatory reactions (1Mayer R.J. Marshall L.A. FASEB J. 1993; 7: 339-348Crossref PubMed Scopus (444) Google Scholar, 2Mukherjee A.B. Miele L. Pattabiraman N. Biochem. Pharmacol. 1994; 48: 1-10Crossref PubMed Scopus (188) Google Scholar). It is found associated with several cells and tissues or is present extracellularly when released in response to proinflammatory mediators such as interleukin-1, interleukin-6, or tumor necrosis factor. The soluble type II 14-kDa PLA2 found in inflammatory fluids, tissue exudates, or serum has been suggested to propagate inflammation through membrane digestion and liberation of proinflammatory lipid mediators. The cell-associated type II PLA2 has been assumed to release AA for lipid mediator generation (1Mayer R.J. Marshall L.A. FASEB J. 1993; 7: 339-348Crossref PubMed Scopus (444) Google Scholar, 2Mukherjee A.B. Miele L. Pattabiraman N. Biochem. Pharmacol. 1994; 48: 1-10Crossref PubMed Scopus (188) Google Scholar, 3Dennis E.A. J. Biol. Chem. 1994; 269: 13057-13060Abstract Full Text PDF PubMed Google Scholar). However, because the 14-kDa PLA2 lacks selectivity for the sn-2 fatty acids of phospholipids and requires much higher Ca2+(mm) than normal cellular Ca2+ level (nm–μm) for activation, it was not certain whether this type of PLA2 contributes to the release of AA and production of eicosanoids. Studies using antisense inhibition and selective inhibitors of different forms of PLA2s have demonstrated that the type II PLA2 participates in AA release and prostaglandin generation in the P388D1macrophages (4Barbour E.A. J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar, J. E.A. 1994; PubMed Scopus Google Scholar, J. E.A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). These have an role of the 14-kDa PLA2 for AA The high molecular mass 85-kDa cPLA2 a for arachidonic acid in the sn-2 of the phospholipids (1Mayer R.J. Marshall L.A. FASEB J. 1993; 7: 339-348Crossref PubMed Scopus (444) Google Scholar, 2Mukherjee A.B. Miele L. Pattabiraman N. Biochem. Pharmacol. 1994; 48: 1-10Crossref PubMed Scopus (188) Google Scholar, 3Dennis E.A. J. Biol. Chem. 1994; 269: 13057-13060Abstract Full Text PDF PubMed Google Scholar, N. PubMed Scopus Google Scholar, L.A. N. Full Text PDF PubMed Scopus Google Scholar, J. J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. J. Biol. Chem. Full Text PDF PubMed Google Scholar). The activity is by PubMed Scopus Google Scholar, R.J. 1993; Full Text PDF PubMed Scopus Google Scholar, J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar, 1994; PubMed Scopus Google J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google and of Ca2+ N. PubMed Scopus Google Scholar, L.A. N. Full Text PDF PubMed Scopus Google Scholar, J. J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. Biol. Chem. Full Text PDF PubMed Google Scholar). These the 85-kDa cPLA2 a for in the liberation of AA from membrane phospholipids for subsequent to eicosanoids. The cPLA2 is in a of cells (1Mayer R.J. Marshall L.A. FASEB J. 1993; 7: 339-348Crossref PubMed Scopus (444) Google Scholar, 2Mukherjee A.B. Miele L. Pattabiraman N. Biochem. Pharmacol. 1994; 48: 1-10Crossref PubMed Scopus (188) Google Scholar, 3Dennis E.A. J. Biol. Chem. 1994; 269: 13057-13060Abstract Full Text PDF PubMed Google Scholar). Although the cPLA2 lacks a in its 1994; PubMed Scopus Google Scholar, Biochem. 1994; PubMed Scopus Google Scholar, PubMed Scopus Google its expression is by various in several cell types J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. J. PubMed Scopus Google Scholar, N. 1993; PubMed Scopus Google Scholar, J. 1994; PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, J. J. 1994; PubMed Scopus Google Scholar, J. 1994; Google Scholar). The cPLA2 has two the region acids the lipid acid and the region acids the L.A. N. Full Text PDF PubMed Scopus Google Scholar, E.A. L.A. J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google Scholar). The region lipid the of cPLA2 from to membrane The region the the J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google Scholar). Several and have also been in the region J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the for is by R.J. 1993; Full Text PDF PubMed Scopus Google Scholar, J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar). such as and also of cPLA2 in R.J. 1993; Full Text PDF PubMed Scopus Google Scholar, J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar, J. PubMed Scopus Google Scholar). the by the lipid and of the region play an role in the of cPLA2 and regulation of AA an to further the regulation of the 85-kDa cPLA2, this study was to with the or region of cPLA2 by a human cDNA using the two hybrid the unique member of S100 family of calcium-binding proteins, was found to with the region of demonstrated that p11 associated with cPLA2 and the cPLA2 activity in vitro. The was from a human bronchial epithelial cell line (BEAS 2B p11 and of p11 expression in the BEAS 2B cells by antisense RNA the inhibition of p11 cPLA2, in an increased PLA2 activity as well as an increased AA This study a mechanism of cPLA2 regulation by the S100 the for the acids as well as for was used to the cPLA2 cDNA to the and to the by using human cPLA2 cDNA as the L.A. N. Full Text PDF PubMed Scopus Google Scholar). The cPLA2 cDNA into in the and with the to the the cPLA2 cDNA two synthesized to the L.A. N. Full Text PDF PubMed Scopus Google Scholar). The for the was of the from the to the to of the the and for in to the to of the the The for the cPLA2 cDNA was of the to to of the the and for in to the to of the region and the The cDNA was The into the using the The released from the by digestion and into the The and of the by The the cPLA2 cDNA to the cPLA2 was as The the cPLA2 cDNA to the cPLA2 was as These used to The the or for and for activity using a The activity was in or The cells or for using the The of the was by the that the cPLA2 and cPLA2 with the human cDNA in was to with The was used for with the and or by the PubMed Scopus Google Scholar). The cells with or by with from the human cDNA in the and a of for of and for The to and for activity using as in liquid for and in the was and by and well for the from the using a PubMed Scopus Google Scholar). The was to an a to the hybrid that The cells a of acids and and the was using a J. Scholar). of the cDNA was by using a to the and the of the and the protein. to the to the of the for p11 expression in human p11 cDNA was by and using human The synthesized to the human p11 cDNA PubMed Scopus Google was of the to of the cDNA to the the and to of the cDNA in the The into the using the The released from the by digestion and and into the expression to The and of the was by The p11 as a a of the The by digestion with was used for of the p11 for activity of soluble PubMed Scopus Google Scholar). The was into a the the of the expression of The p11 was using to the The was with and the released p11 was and further by gel using The p11 was used for subsequent of the of p11 cPLA2 the in cPLA2 activity is the of the R.J. J. Biol. Chem. Full Text PDF PubMed Google we used the membrane from the BEAS 2B cells as cPLA2 the membrane the BEAS 2B cells in with acid in of AA to membrane may be the of the cells with and to of AA in various of phospholipids J. E.A. 1994; PubMed Scopus Google Scholar, J. E.A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, J. 1993; Google Scholar). The cells with for to to for the of in phospholipids, the in and the the cells with for this the of AA in phospholipids from that in that not is the that of the The cells and in of by The was for to and The low was for to a cytosolic and a membrane The was and the was in and and in for as cPLA2 was of phospholipids by a gel with using of and The phospholipids by with cPLA2 activity was BEAS 2B cell membrane and human cPLA2 in a of The cPLA2 was by the and is from of the Ca2+ a system was used PubMed Scopus Google Scholar). the physiological cellular Ca2+ level is level in normal cells and and the cPLA2 activity is of a Ca2+ free was used for the and The was by the of to the The for and by the of of acid and free of free fatty acid was using gel as J. 1994; PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). The of p11 was as a of the by cPLA2 in p11 the the was synthesized from the by the in and using the of was in for by the of of with and for from reactions and in for of the of the synthesized was with of human cPLA2 in of and for The cPLA2 was by and is from of cPLA2 and of and the was a for by in a for The was and the was with of and by with of was to the and the was for polyacrylamide using The gel was and to the of the cytosolic proteins, the BEAS 2B cells with for The cells in of and and the cytosolic was as The cytosolic from and in for the cytosolic of was to an of and and of cPLA2 The for of was to and the was for by in a for The was and the was with of by with of was to the and the was for polyacrylamide using The a was with and with a of The with a of and using the cytosolic as using BEAS 2B of the was with of and of the with of was to the and the was for of polyacrylamide using The a membrane that was with and with a of The with a of and using the the antisense p11 expression human p11 cDNA was released from of the the and into the mammalian expression in the antisense The the human region to expression of the p11 in mammalian The also the and region to the expression of the and the of to in cell that BEAS 2B The cells in to of with of cells with expression to the of and for of the was and the was for The cells in of cells and the cells of the cells in the of selective the of p11, cPLA2, and cytosolic was from cells with or with The cells cells when the The cells in the and and the cytosolic was as The cytosolic was to and using a of or II The with a of of p11 and or of and using the cytosolic and with was as using BEAS 2B cells with the antisense p11 or the of the with of was to the and the was for of polyacrylamide using The a membrane that was with and with a of or II The with a of of and using the PLA2activity was as J. 1994; PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). of the cells with or cells with the with type I when The of cells in was by cellular level using Biochem. Scopus Google Scholar). of the cells with and the cells with the antisense p11 in when the cells for with acid in of release the cells with and and of The by and by high pressure liquid as J. 1994; PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). The arachidonic acid of was and for of release of the cells with and the cells with the antisense p11 with type I cells when when the cells The cells for with acid in with HBSS, of with was to and the cells for The from as for further The by and by high pressure liquid as The arachidonic acid of was and for an to that with the or the of the 85-kDa cPLA2 different of the cPLA2 cDNA into to the the and the or of the cPLA2 protein. the the cPLA2 cDNA to the cPLA2 or the cPLA2 cDNA to the cPLA2 was used to the The or was used for subsequent with from a human cDNA in the this to with the region of cPLA2 protein. However, was found to with the region of the the the into the in the or of or results in the activity when with the These also into results in the activity in the is the of a different from that used to in two in the of the two two hybrid in and requires of the to the 1993; Google Scholar). we that the the for of the in the of the and the cDNA of human p11 PubMed Scopus Google a member of the S100 The from the two hybrid screen that p11 to cPLA2 protein. study the of p11 cPLA2 to the of p11 cPLA2 vitro. The membrane was with of human cPLA2 with various of human was used as a for the in PLA2 activity as E.A. J. Biol. Chem. Full Text PDF PubMed Google Scholar). in p11 a inhibition of the These results that p11 interacts with the cPLA2 and inhibits the cPLA2 whether the of p11 is to the inhibition of cPLA2 by p11 was various of in p11 different These that the inhibition of cPLA2 by p11 is through an p11 and the of and II inhibition of with various of in different membrane with of human cPLA2 in the of of human with II in the membrane of was with of cPLA2 in the of of human p11 of II. The was by the of to the and the for of free fatty acid was using as the p11 is associated with the II to form II in we also whether the of p11 cPLA2 activity may be by the of II. The of II or II and p11 cPLA2 activity was the in in II This was not because II from its to various PLA2s the in II certain cPLA2 this was than the inhibition by The of II and p11 to These results that II not the of p11 cPLA2 p11 is to and cPLA2, and the of II is not for the further the p11 and cPLA2, we used the in human p11 and human cPLA2 to in vitro. The expression the and human p11 cDNA was used as the to p11 by the and The synthesized the as well as other that to be the products from The in p11 was with cPLA2 to the of in p11 was not by in the of cPLA2 it was with This demonstrates the of in vitro. The results demonstrated that p11 to cPLA2 in two hybrid and in of synthesized p11 and further the p11 and cPLA2 in human to the of in cells p11 and the of cPLA2 in the BEAS 2B human bronchial epithelial cell line J. 1994; PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). Using the expression of p11 was also found in the BEAS 2B cells we that the be from the BEAS 2B cells in p11 was from the BEAS 2B cell by cPLA2 This demonstrates the of in the BEAS 2B to the with a to p11 not not of p11-cPLA2complex from BEAS 2B of the cytosolic and of cytosolic of cytosolic cytosolic with of cPLA2 or of in of for the cytosolic cPLA2 or of was to and the was a for The and with of by was to the and the for and to The p11 was by using p11 and as The of p11 was have that p11 to cPLA2 and inhibits the in vitro. study further the of p11 PLA2 activity and AA release in human we used the antisense RNA to the expression of p11 and to the PLA2 activity and AA release in the BEAS 2B The expression of p11 was by the antisense inhibition The antisense inhibition of p11 expression not cellular production of II. the of p11 and of II with cPLA2 from cells and from cells with the p11 antisense was of from cells and from cells with the antisense was using the was and the with to p11 or to II the antisense cells p11 of II of with demonstrated p11 and II to cPLA2 in the antisense cells than in cells the PLA2 activity and AA release from The in PLA2 activity in cells with was higher than in cells with The release of prelabeled AA from cells with was two or release of AA from cell was a of with for cells with released of the released from cells with the because cPLA2 may be by in intracellular AA release with the was with the release of prelabeled AA from cells with was higher than from cells with These results that p11 inhibits PLA2 activity and AA release in normal BEAS 2B expression of p11 in the antisense cells the of cPLA2 by p11, results in an in PLA2 activity and AA release from BEAS 2B cells with antisense The cells for with in of the cells with in of for and the for The from to The by and by as The in the to the of AA The is a of This study a novel mechanism for the regulation of 85-kDa that p11, a unique member of the S100 family of calcium-binding proteins, interacts with the carboxyl region of cPLA2 and inhibits the cPLA2 The p11 and cPLA2 was by a human cDNA using a two hybrid demonstrated that p11 associated with cPLA2 in vitro. Using membrane as p11 was found to the activity of cPLA2 in vitro. The inhibition of cPLA2 activity by p11 was of These results demonstrated that p11 interacts with cPLA2 and inhibits the cPLA2 to study the role of p11 in human The was from the BEAS 2B human bronchial epithelial cell line cPLA2 and Selective inhibition of p11 expression in the BEAS 2B cells by antisense RNA a of cellular p11 and in an increased PLA2 activity as well as an increased release of prelabeled the in and in a novel mechanism for the regulation of the S100 The S100 are a group of low molecular mass proteins, the of the in Biochem. Full Text PDF PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). The of is the of the two and and the Ca2+ as the other such as the family and the family and family the S100 have two and The acid of calcium-binding and of that this group of from a Biochem. Full Text PDF PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). The of the S100 are has been to of the to The to a in the S100 proteins, and this may the This of and of the activity of the is to that with family of calcium-binding the Biochem. Full Text PDF PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). the of S100 is cell types, the S100 may be involved in the of an in intracellular in a cell Biochem. Full Text PDF PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). p11 was as a for the PubMed Scopus Google Scholar). Although p11 with the S100 it not because of acid and in the two PubMed Scopus Google Scholar). This is an to the by other S100 p11 interacts with the II N. Biol. Google Scholar, Biochem. Scopus Google Scholar). The p11 and II are to other in a that is present in tissues and p11 forms a that two II the of a II as a or to p11 the p11 has been found as of a with II in tissues II is present in or in N. Biol. Google Scholar, Biochem. Scopus Google Scholar). However, this may with different cell The expression of p11 and II is not and the of p11 to II with different cell types J. Biol. Chem. Full Text PDF PubMed Google Scholar). the a of p11 II the RNA and with the p11 in the J. 1993; Google Scholar). of cells results in a in II and the of the J. 1993; Google Scholar). The associated with membrane and through the of II with the phospholipids and of the The of II with and membrane phospholipids is Ca2+ and p11 the Ca2+ of with the a than increased with II Biochem. J. PubMed Scopus Google Scholar). It remains whether p11 is also to with other protein. results that the 85-kDa cPLA2, a unique calcium-binding is a novel that interacts with from the two hybrid screen demonstrated that p11 associated with cPLA2 in the acid involved in the is the region of the cPLA2 is found to with the The of p11 and cPLA2 was also found in using human cPLA2 and the in human p11 we found that p11 and cPLA2 with other in vitro. Furthermore, the of was also from cells p11 and cPLA2 by results a p11 and the region of to cPLA2 the other that to the of p11 to cPLA2 may the activity of cPLA2, we the of p11 the activity of human cPLA2 in of the The is the of membrane a of phospholipids as cPLA2 to the in cPLA2, p11, and This was by and L.A. N. Full Text PDF PubMed Scopus Google used the cell membrane as cPLA2 this the membrane with from the BEAS 2B of the is the low Ca2+ used in the the cPLA2 is by of Ca2+ and the physiological cellular Ca2+ level is level as well in normal cells and in we used the Ca2+ free Ca2+ in the for the we found that p11 cPLA2 activity in a and this is not These results that p11 to cPLA2 and inhibits the cPLA2 activity in vitro. Although the mechanism for the inhibition of cPLA2 by p11 is not it is that this is to the p11 and because p11 not to phospholipids PubMed Scopus Google Scholar, N. Biol. Google and the is not we a p11 and cPLA2, and it is that the of p11 to cPLA2 results in the inhibition of cPLA2 However, it remains to be the of p11 to cPLA2 inhibits the cPLA2 The may include of the process of cPLA2, of cPLA2, or of of cPLA2 with membrane study further the of p11 PLA2 activity and AA release in human we used the antisense RNA to the expression of p11 and to the PLA2 activity and AA release in the BEAS 2B The release of prelabeled AA from cells with p11 expression was higher than from the cells The cytosolic from the cells also an increased PLA2 These results that p11 inhibits PLA2 activity and AA release in the BEAS 2B p11 expression the of p11 cPLA2 and the PLA2 activity and the release of from the These results that p11 the release of AA for eicosanoid production in cells by cellular cytosolic PLA2 It is well that p11 to a member of the and N. Biol. Google Scholar, Biochem. Scopus Google Scholar, Full Text PDF PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, The Scholar, 1994; Full Text PDF PubMed Scopus Google Scholar, 1994; PubMed Scopus Google Scholar, 1994; PubMed Scopus Google Scholar). The are in The of the are not well have been suggested to in a of physiological including inhibition of PLA2 The Scholar). The of of the family is to phospholipids, with cellular membranes in This is by the that to of acid with a acid in the are with the of II can as or The II is of two of II and two of p11 N. Biol. Google Scholar, Biochem. Scopus Google Scholar). The II of two The the acids and the for p11 and the and The acids of II to p11 an The and can be by and the by the PubMed Scopus Google Scholar). The carboxyl of II of the acid that to phospholipids, and Although p11 not to and phospholipids, II has and of of the the of inflammatory have been to selective inhibitors of The or found to cellular PLA2 activity in various cell types The Scholar, R.J. J. Pharmacol. PubMed Scopus Google Scholar). using the 14-kDa PLA2 demonstrated that the PLA2 activity was by and this to the that the inhibition of 14-kDa PLA2 by was the mechanism of the for The Scholar, R.J. J. Pharmacol. PubMed Scopus Google Scholar, R.J. L. PubMed Scopus Google Scholar, J. PubMed Scopus Google Scholar, Full Text PDF PubMed Scopus Google Scholar). However, subsequent to the 14-kDa PLA2 and it was found that the in inhibition of 14-kDa PLA2 by be by the E.A. J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. Biol. Chem. Full Text PDF PubMed Google Scholar, L. PubMed Scopus Google Scholar). The of inhibition was to the than the and the of inhibition not with a or the of 14-kDa PLA2 was to than to with the 14-kDa have demonstrated that p11 interacts with the region of cPLA2 and inhibits the cPLA2 the inhibition of cPLA2 by p11 is of this is to a p11 and p11 is associated with the II to form II in we also whether the of p11 cPLA2 activity may be by the of II. The of II or II and p11 cPLA2 activity was the in found that II cPLA2 This was as because II from its to various PLA2s the in II certain cPLA2 this was than the inhibition by The of II and p11 to These results that II not the of p11 cPLA2 p11 is to and J. and J. L. the for the human cPLA2, and human cPLA2 and J. and of for the BEAS 2B