PMID:15967158,15051069 For example, PAMPs produced by cellwall components of Gram-negative bacteria (LPS) are recognized by TLR4; it involves the binding of LPS to a serum protein, lipopolysaccharide-binding protein (LPB), which in turn binds to membrane CD14, which transfers the complex to TLR4 in an MD-2-dependent manner

PMID:15967158 They are then released into the bloodstream and transported to sites in or close to the POA that react to their stimulation by selectively expressing COX-2 and mPGES-1.

PMID:15967158 They are then released into the bloodstream and transported to sites in or close to the POA that react to their stimulation by selectively expressing COX-2 and mPGES-1.

PMID:15967158 They are then released into the bloodstream and transported to sites in or close to the POA that react to their stimulation by selectively expressing COX-2 and mPGES-1.

PMID:15967158 They are then released into the bloodstream and transported to sites in or close to the POA that react to their stimulation by selectively expressing COX-2 and mPGES-1.

PMID:15967158 They are then released into the bloodstream and transported to sites in or close to the POA that react to their stimulation by selectively expressing COX-2 and mPGES-1.

PMID:15967158 They are then released into the bloodstream and transported to sites in or close to the POA that react to their stimulation by selectively expressing COX-2 and mPGES-1.

PMID:15967158 They are then released into the bloodstream and transported to sites in or close to the POA that react to their stimulation by selectively expressing COX-2 and mPGES-1.

PMID: 15967158,9748570,9880592,12957837,9917869,10578230 In support, LPS, like IL-1beta, induces these enzymes in endothelial cells of the cerebral microvasculature, including in the OVLT, the choroid plexi and the leptomeninges

PMID: 15967158,9748570,9880592,12957837,9917869,10578230 In support, LPS, like IL-1beta, induces these enzymes in endothelial cells of the cerebral microvasculature, including in the OVLT, the choroid plexi and the leptomeninges

PMID: 15967158,8027674,12376404,14977603 Indeed, the activation by LPS of group IV cytosolic phospholipase (cPL)A2 is significantly delayed in vitro and in vivo

PMID:15967158,15051069 For example, PAMPs produced by cellwall components of Gram-negative bacteria (LPS) are recognized by TLR4; it involves the binding of LPS to a serum protein, lipopolysaccharide-binding protein (LPB), which in turn binds to membrane CD14, which transfers the complex to TLR4 in an MD-2-dependent manner

PMID: 15967158,7664696,8193936 the expression of c-fos in the nucleus of the solitary tract (NTS, the primary projection area of the vagus nerves) is enhanced after i.v. and i.p. IL-1beta and i.v. LPS

PMID: 15967158,7664696,8193936 the expression of c-fos in the nucleus of the solitary tract (NTS, the primary projection area of the vagus nerves) is enhanced after i.v. and i.p. IL-1beta and i.v. LPS

PMID: 15967158 Together, these data, plus others not described, thus substantiate the notion that circulating LPS arriving in the liver could activate Kc to produce and release TNFalpha, IL-1beta and IL-6

PMID: 15967158 Together, these data, plus others not described, thus substantiate the notion that circulating LPS arriving in the liver could activate Kc to produce and release TNFalpha, IL-1beta and IL-6

PMID: 15967158 Together, these data, plus others not described, thus substantiate the notion that circulating LPS arriving in the liver could activate Kc to produce and release TNFalpha, IL-1beta and IL-6

PMID: 15967158 Together, these data, plus others not described, thus substantiate the notion that circulating LPS arriving in the liver could activate Kc to produce and release TNFalpha, IL-1beta and IL-6

PMID: 15967158 Together, these data, plus others not described, thus substantiate the notion that circulating LPS arriving in the liver could activate Kc to produce and release TNFalpha, IL-1beta and IL-6

PMID: 15967158 Together, these data, plus others not described, thus substantiate the notion that circulating LPS arriving in the liver could activate Kc to produce and release TNFalpha, IL-1beta and IL-6

PMID: 15967158 Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of surface-bound and fluid-phase C3b and iC3b

PMID: 15967158 Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of surface-bound and fluid-phase C3b and iC3b

PMID:15967158,15051069 For example, PAMPs produced by cellwall components of Gram-negative bacteria (LPS) are recognized by TLR4; it involves the binding of LPS to a serum protein, lipopolysaccharide-binding protein (LPB), which in turn binds to membrane CD14, which transfers the complex to TLR4 in an MD-2-dependent manner

PMID: 15967158 Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of surface-bound and fluid-phase C3b and iC3b

PMID: 15967158 Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of surface-bound and fluid-phase C3b and iC3b

PMID: 15967158 Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of surface-bound and fluid-phase C3b and iC3b

PMID: 15967158 Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of surface-bound and fluid-phase C3b and iC3b

PMID: 15967158 Indeed, the i.v. administration of LPS triggers within 2 min the C cascade via the alternative pathway, resulting in the production in blood of C4a, C3a and C5a and of surface-bound and fluid-phase C3b and iC3b

PMID: 15967158 PGE2, under these conditions, could be generated via the hydrolysis of membrane-associated phosphoinositide (PI, which has a high arachydonoyl chain content) by PI-specific phospholipase C (PI-PLC) PMID: 15967158,5284360 Vane demonstrated that aspirin blocks prostaglandin synthesis

PMID: 15967158 indeed, arachidonic acid (AA) liberation by PI-PLC is 10-fold more rapid (within seconds) than that mediated by cPLA2 PMID: 15967158 Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the subsequent conversion of this AA to PGE2 is catalyzed by COX-1

PMID: 15967158, indeed, arachidonic acid (AA) liberation by PI-PLC is 10-fold more rapid (within seconds) than that mediated by cPLA2

PMID: 15967158 Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the subsequent conversion of this AA to PGE2 is catalyzed by COX-1

PMID: 15967158 Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the subsequent conversion of this AA to PGE2 is catalyzed by COX-1

PMID:15967158,15051069 For example, PAMPs produced by cellwall components of Gram-negative bacteria (LPS) are recognized by TLR4; it involves the binding of LPS to a serum protein, lipopolysaccharide-binding protein (LPB), which in turn binds to membrane CD14, which transfers the complex to TLR4 in an MD-2-dependent manner

PMID: 15967158 Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the subsequent conversion of this AA to PGE2 is catalyzed by COX-1

PMID: 15967158 Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the subsequent conversion of this AA to PGE2 is catalyzed by COX-1

PMID: 15967158 Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the subsequent conversion of this AA to PGE2 is catalyzed by COX-1

PMID: 15967158 Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the subsequent conversion of this AA to PGE2 is catalyzed by COX-1

PMID: 15967158 Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the subsequent conversion of this AA to PGE2 is catalyzed by COX-1

PMID: 15967158 Moreover, PI-PLC is reportedly activated by C, but not by LPS or IL-1beta, and the subsequent conversion of this AA to PGE2 is catalyzed by COX-1 PMID: 15967158,5284360 Vane demonstrated that aspirin blocks prostaglandin synthesis

PMID: 15967158,11113021,11113018 Thus, it is now generally believed that cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 selectively induced by pyrogenic cytokines catalyze its production, and that it acts in the preoptic-anterior hypothalamus (POA), the brain site of the primary thermoregulatory controller PMID: 15967158 The second step of the conventional sequence asserts that the synthesis of PGE2 is effected in the POA via catalysis by COX-2 and mPGES-1 PMID: 15967158,5284360 Vane demonstrated that aspirin blocks prostaglandin synthesis

PMID: 15967158,11113021,11113018 Thus, it is now generally believed that cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 selectively induced by pyrogenic cytokines catalyze its production, and that it acts in the preoptic-anterior hypothalamus (POA), the brain site of the primary thermoregulatory controller PMID: 15967158 The second step of the conventional sequence asserts that the synthesis of PGE2 is effected in the POA via catalysis by COX-2 and mPGES-1 PMID: 15967158,5284360 Vane demonstrated that aspirin blocks prostaglandin synthesis

PMID: 15967158,9453538,1570314,7631045,10223523 Moreover, the transcription and translation of inducible COX-2 and mPGES-1 by inflammatory stimuli, LPS and IL-1beta alike, require at least 1 h in vitro

PMID: 15967158,9453538,1570314,7631045,10223523 Moreover, the transcription and translation of inducible COX-2 and mPGES-1 by inflammatory stimuli, LPS and IL-1beta alike, require at least 1 h in vitro

PMID:15967158 They are then released into the bloodstream and transported to sites in or close to the POA that react to their stimulation by selectively expressing COX-2 and mPGES-1.

PMID: 15967158,14977603,15492017,11262580,15353338,15373964 the consensus has now developed that the febrile response to LPS (and also to live bacteria is probably not initiated by newly generated, blood-borne pyrogenic cytokines, but rather by the production of PGE2 directly stimulated in the periphery by the exogenous pyrogens themselves PMID: 15967158,5284360 Vane demonstrated that aspirin blocks prostaglandin synthesis

PMID: 15967158 In conscious guinea pigs, Tc and plasma PGE2 rise simultaneously and concurrently with the first appearance in Kc of i.v. or i.p. injected LPS. PMID: 15967158,9100920,9608013,10600909 The associated Kc uptake of i.v. or i.p. LPS, the rise in plasma PGE2 and the febrile response are prevented by pre-treatment with gadolinium chloride, an agent that temporarily depletes Kc, or with CVF, a decomplementing toxin PMID: 15967158 Pre-treatment with PGE2 anti-serum (which does not cross the BBB) reduces the rises in Tc and plasma and preoptic PGE2 induced by i.v. LPS in conscious guinea pigs

PMID: 15967158 The addition of serum C alone or in combination with LPS, but not of LPS alone, to primary Kc from guinea pigs and mice in vitro provokes the virtually immediate, near-maximal release of PGE2 by these cells; this response is catalyzed nondifferentially by COX-1 and COX-2 (constitutive in Kc).

PMID: 15967158 The addition of serum C alone or in combination with LPS, but not of LPS alone, to primary Kc from guinea pigs and mice in vitro provokes the virtually immediate, near-maximal release of PGE2 by these cells; this response is catalyzed nondifferentially by COX-1 and COX-2 (constitutive in Kc).

PMID: 15967158 The addition of serum C alone or in combination with LPS, but not of LPS alone, to primary Kc from guinea pigs and mice in vitro provokes the virtually immediate, near-maximal release of PGE2 by these cells; this response is catalyzed nondifferentially by COX-1 and COX-2 (constitutive in Kc).

PMID: 15967158 The addition of serum C alone or in combination with LPS, but not of LPS alone, to primary Kc from guinea pigs and mice in vitro provokes the virtually immediate, near-maximal release of PGE2 by these cells; this response is catalyzed nondifferentially by COX-1 and COX-2 (constitutive in Kc).

PMID: 15967158,4145320 NE also stimulates the release of PGE2 in brain tissue in vitro

PMID: 15967158,4145320 NE also stimulates the release of PGE2 in brain tissue in vitro PMID: 15967158,5284360 Vane demonstrated that aspirin blocks prostaglandin synthesis

PMID:15967158 They are then released into the bloodstream and transported to sites in or close to the POA that react to their stimulation by selectively expressing COX-2 and mPGES-1.

PMID:15967158 They are then released into the bloodstream and transported to sites in or close to the POA that react to their stimulation by selectively expressing COX-2 and mPGES-1.