PMID: 1757110, 3760571, 3108379 The fact that differences in TNF-o~ release could be measured at the protein level within 4 h of addition of priming/activating signals stimulated us to begin looking at changes in expression of other early response genes at the mRNA level, especially those like c-fos, c-myc, JE and KC which are known to be induced by LPS

PMID: 1757110, 3497923, 2537468 Expression of both c-fos and c-jun is stimulated by TNF-alpha.

PMID: 1757110 In the case of c-fos, the protein product for the gene dimerises with c-jun to form the TRE binding protein complex AP-1, c-fos itself having both TRE and CRE in its promoter region.

PMID: 1757110 In the case of c-fos, the protein product for the gene dimerises with c-jun to form the TRE binding protein complex AP-1, c-fos itself having both TRE and CRE in its promoter region.

PMID: 1757110 In the case of c-fos, the protein product for the gene dimerises with c-jun to form the TRE binding protein complex AP-1, c-fos itself having both TRE and CRE in its promoter region.

PMID: 1757110 TNF-o~ stimulates prolonged expression at the mRNA level contrasting with transient induction observed with the phorbol ester TPA.

PMID: 1757110, 2279740, 2175327 In the context of the L. major model, Liew and co-workers have shown that, in the presence of 10ng/ml LPS, recombinant TNF-et acts synergistically with interferon-3, to give maximal production of INO and antileishmanial activity. PMID: 1757110, 2999236 This was confirmed by Green and co-workers [47] who showed that neutralizing anti-TNF-a antibodies blocked production of INO and antileishmanial activity in interferon-3, primed peritoneal macrophages. PMID: 1757110, 1712077, 2432665, 3242600 In this system, L-arginine is oxidised by an inducible NADPHdependent enzyme (NO synthase) to yield L-citrulline, nitrite and nitrate, with highly reactive nitric oxide (NO) produced as an intermediate. The degree of kill correlated well with the levels of nitrites measured in the supernatants at 72 h, and inclusion of 200 #M L-NMMA, a competitive inhibitor of the L-arginine dependent pathway for the synthesis of INO, inhibited the killing

PMID: 1757110 This could involve differences in down regulation of LPS or TNF-a receptors, or a cAMPdependent down regulation of TNF-o~ production. In preliminary experiments (T. I.A. Roach and J.M. Blackwell, unpublished) we have established that either addition of exogenous prostaglandin E2, or inhibition of cAMP catabolism with theophylline, reduces TNF-ot release.

PMID: 1757110, 2279740, 2175327 In the context of the L. major model, Liew and co-workers have shown that, in the presence of 10ng/ml LPS, recombinant TNF-et acts synergistically with interferon-3, to give maximal production of INO and antileishmanial activity. PMID: 1757110, 2999236 This was confirmed by Green and co-workers [47] who showed that neutralizing anti-TNF-a antibodies blocked production of INO and antileishmanial activity in interferon-3, primed peritoneal macrophages. PMID: 1757110, 1712077, 2432665, 3242600 In this system, L-arginine is oxidised by an inducible NADPHdependent enzyme (NO synthase) to yield L-citrulline, nitrite and nitrate, with highly reactive nitric oxide (NO) produced as an intermediate. The degree of kill correlated well with the levels of nitrites measured in the supernatants at 72 h, and inclusion of 200 #M L-NMMA, a competitive inhibitor of the L-arginine dependent pathway for the synthesis of INO, inhibited the killing

PMID: 1757110, 3917283, 2112157 Previous studies have shown, for example, that L. donovani is a potent stimulator of prostaglandin E2 synthesis in BALB/ c (Lsh s) macrophages, and that preinfection of macrophages selectively diminishes IL-1 (but not TNF-ot) production.

PMID: 1757110, 3917283, 2112157 Previous studies have shown, for example, that L. donovani is a potent stimulator of prostaglandin E2 synthesis in BALB/ c (Lsh s) macrophages, and that preinfection of macrophages selectively diminishes IL-1 (but not TNF-ot) production.

PMID: 1757110, 3760571, 3108379 The fact that differences in TNF-o~ release could be measured at the protein level within 4 h of addition of priming/activating signals stimulated us to begin looking at changes in expression of other early response genes at the mRNA level, especially those like c-fos, c-myc, JE and KC which are known to be induced by LPS

PMID: 1757110, 1707920 More recently, Descoteaux and co-workers have shown that parasite-derived lipophosphoglycan (LPG) stimulates rapid expression of both c-fos and TNF-a genes

PMID: 1757110, 1707920 More recently, Descoteaux and co-workers have shown that parasite-derived lipophosphoglycan (LPG) stimulates rapid expression of both c-fos and TNF-a genes

PMID: 1757110 LPG induced a rapid down-modulation of TNF-a receptors but did not impair stimulation of expression of c-fos by the cAMP analogue, dibutyryl cAMP.

PMID: 1757110 LPG induced a rapid down-modulation of TNF-a receptors but did not impair stimulation of expression of c-fos by the cAMP analogue, dibutyryl cAMP.

PMID: 1757110 LPG induced a rapid down-modulation of TNF-a receptors but did not impair stimulation of expression of c-fos by the cAMP analogue, dibutyryl cAMP.

PMID: 1757110, 2999236 The LPS itself acts as a potent stimulator of TNF-ct release, which may then form an autocrine loop acting back on the macrophage. PMID: 1757110 This could involve differences in down regulation of LPS or TNF-a receptors, or a cAMPdependent down regulation of TNF-o~ production. In preliminary experiments (T. I.A. Roach and J.M. Blackwell, unpublished) we have established that either addition of exogenous prostaglandin E2, or inhibition of cAMP catabolism with theophylline, reduces TNF-ot release.

PMID: 1757110, 3745439, 2451695, 2497225 NO mediates L-arginine dependent tumour cyo tostasis during co-culture with interferon-7 and LPS activated macrophages, possibly via nitrosylation reactions which remove labile iron atoms from Fe-S prosthetic groups of aconitase and complexes I and II of the mitochondrial electron transport system

PMID: 1757110, 2279740, 2175327 In the context of the L. major model, Liew and co-workers have shown that, in the presence of 10ng/ml LPS, recombinant TNF-et acts synergistically with interferon-3, to give maximal production of INO and antileishmanial activity. PMID: 1757110, 2999236 This was confirmed by Green and co-workers [47] who showed that neutralizing anti-TNF-a antibodies blocked production of INO and antileishmanial activity in interferon-3, primed peritoneal macrophages. PMID: 1757110, 1712077, 2432665, 3242600 In this system, L-arginine is oxidised by an inducible NADPHdependent enzyme (NO synthase) to yield L-citrulline, nitrite and nitrate, with highly reactive nitric oxide (NO) produced as an intermediate. The degree of kill correlated well with the levels of nitrites measured in the supernatants at 72 h, and inclusion of 200 #M L-NMMA, a competitive inhibitor of the L-arginine dependent pathway for the synthesis of INO, inhibited the killing

PMID: 1757110, 3760571, 3108379 The fact that differences in TNF-o~ release could be measured at the protein level within 4 h of addition of priming/activating signals stimulated us to begin looking at changes in expression of other early response genes at the mRNA level, especially those like c-fos, c-myc, JE and KC which are known to be induced by LPS

PMID:1757110 In this case, the parasite (L. major) itself acted as the stimulus for TNF-a release by the macrophage. PMID: 1757110 This could involve differences in down regulation of LPS or TNF-a receptors, or a cAMPdependent down regulation of TNF-o~ production. In preliminary experiments (T. I.A. Roach and J.M. Blackwell, unpublished) we have established that either addition of exogenous prostaglandin E2, or inhibition of cAMP catabolism with theophylline, reduces TNF-ot release.

PMID: 1757110 The magnitude of this response was enhanced in macrophages preinfected with L. donovani amastigotes, suggesting again that the parasite itself may act as a trigger for TNF-ct production/release. PMID: 1757110 This could involve differences in down regulation of LPS or TNF-a receptors, or a cAMPdependent down regulation of TNF-o~ production. In preliminary experiments (T. I.A. Roach and J.M. Blackwell, unpublished) we have established that either addition of exogenous prostaglandin E2, or inhibition of cAMP catabolism with theophylline, reduces TNF-ot release.

PMID: 1757110, 1712077, 2432665, 3242600 In this system, L-arginine is oxidised by an inducible NADPHdependent enzyme (NO synthase) to yield L-citrulline, nitrite and nitrate, with highly reactive nitric oxide (NO) produced as an intermediate.

PMID: 1757110, 3760571, 3108379 The fact that differences in TNF-o~ release could be measured at the protein level within 4 h of addition of priming/activating signals stimulated us to begin looking at changes in expression of other early response genes at the mRNA level, especially those like c-fos, c-myc, JE and KC which are known to be induced by LPS

PMID: 1757110, 3760571, 3108379 The fact that differences in TNF-o~ release could be measured at the protein level within 4 h of addition of priming/activating signals stimulated us to begin looking at changes in expression of other early response genes at the mRNA level, especially those like c-fos, c-myc, JE and KC which are known to be induced by LPS PMID: 1757110 Priming with 33 units/ml interferon-3, along with l0 ng/ml LPS induced much higher levels of KC

PMID: 1757110 Priming with 33 units/ml interferon-3, along with l0 ng/ml LPS induced much higher levels of KC

PMID: 1757110 For c-fos, differences in expression are observed within 20min following stimulation with PMA plus ionophore. In this case, however, resistant macrophages down-regulate expression from a higher baseline level while susceptible macrophages show enhanced expression over the 20-min time course.

PMID: 1757110, 3497923, 2537468 Expression of both c-fos and c-jun is stimulated by TNF-alpha.

PMID: 1757110, 3497923, 2537468 Expression of both c-fos and c-jun is stimulated by TNF-alpha.