Cytokine-induced expression of inducible nitric oxide synthase (iNOS) and concomitant production of nitric oxide (NO) involve activation of mitogen-activated protein (MAP) kinases and are in most cases mediated by the transcription factor NF-kappaB. We investigated the role of p38 MAP kinase activation and IkappaB phosphorylation in iNOS expression in a novel iNOS-inducing model in mouse macrophages. Deprivation of serum from the culture medium of RAW 264.7 cells up-regulated iNOS and NO production, which were inhibited by 4-hydroxy-2-nonenal (HNE), a component of oxidatively modified low-density lipoprotein (oxLDL). Serum withdrawal induced phosphorylation of Akt, IkappaB, and p38 MAP kinase. Pretreatment with the potent PI3 kinase inhibitor wortmannin, the NF-kappaB inhibitor PDTC or the specific p38 MAP kinase inhibitor SB203580 each partially attenuated the induction of iNOS and NO production, demonstrating that both p38 activation and IkappaB phosphorylation are required for iNOS expression. SB203580, however, did not prevent the phosphorylation of Akt and IkappaB, suggesting that the p38 MAP kinase signal contributes to iNOS gene expression through an IkappaB-phosphorylation-independent pathway. HNE, which markedly inhibited iNOS expression and NO production, prevented the serum withdrawal-triggered IkappaB phosphorylation but not that of Akt or p38 MAP kinase. A high concentration of HNE stimulated dephosphorylation of IkappaB but promoted activation of p38 MAP kinase. Taken together, these results suggest that NF-kappaB and p38 MAP kinase lie in separate signal pathways for serum deprivation-stimulated iNOS expression and NO production. HNE selectively suppresses the former pathway, targeting a site downstream of Akt.

Aldehydes↗

PubMedDate not supplied

Inhibitory effect of bestatin on the growth of human lymphocytes.

Bestatin at mid to high concentration had inhibitory effect to [3H]thymidine incorporation of human lymphocytes. It also decreased the PHA-P, Con A and PWM-induced mitogenicity of human lymphocytes. On the contrary, bestatin had growth stimulatory effect to murine lymphocytes, and enhanced the Con A, LPS-induced mitogenicity of murine lymphocytes. These growth inhibitory (human) and stimulatory (mouse) effect of bestatin was found to be independent of adherent cells (macrophage and dendritic cell), indicatory directly working to T or B lymphocytes.

Aminopeptidases↗

PubMedDate not supplied

Conversion of thyroxine into tri-iodothyronine in zinc deficient rat liver.

Hepatic thyroxine (T4) to tri-iodothyronine (T3) conversion was measured in six animal groups: Group A was fed a severe zinc-deficient diet (1.98 ppm) for 5 weeks; group B was a pair-fed control group for group A; group C was fed a less severe zinc-deficient diet (6.10 ppm) for 5 weeks; group D was a pair-fed control group for group C; group E was fed a zinc-supplemented control diet (90.4 ppm) for 5 weeks; and group F was first fed the severe zinc-deficient diet for 5 weeks and then placed on the zinc-supplemented control diet until a body weight corresponding to the final weight of group E was obtained. Serum T3 and T4 levels and T4 to T3 conversion were significantly reduced in group A. A significant positive correlation was observed between T4 to T3 conversion and alcohol dehydrogenase (zinc-metalloenzyme) activity in liver tissue from the six groups. Thus, it appeared that an appropriate amount of zinc might be one of the factors in thyroxine to tri-iodothyronine conversion in liver tissue normally.

Alcohol Dehydrogenase↗

PubMedDate not supplied

Major basic protein and topical administration of ketotifen in pollinosis under natural allergen provocation.

In this study we investigated the potential relation among subjective symptoms, blood eosinophil counts and the levels of major basic protein (MBP) in serum throughout the pre- to postpollen season. In addition, we compared the effects of topical administration of ketotifen on these parameters between the prophylactic treatment group (n = 10) and the postsymptomatic treatment group (n = 10). We found that (1) the levels of MBP in serum during the season were significantly higher than those before the season and (2) the levels of the above three parameters in the prophylactic treatment group were significantly lower than those in the postsymptomatic treatment group during the season. It was concluded from these results that the action of MBP may be involved in the pathogenesis of allergic rhinitis. Furthermore, for the first time we provided evidence that topical ketotifen administration could suppress the systemic upregulation of the blood eosinophil count and MBP level in subjects with pollinosis.

Administration, Topical↗

PubMedDate not supplied

Eosinophil cationic protein and prophylactic treatment in pollinosis in natural allergen provocation.

In this study, prophylactic treatment with ketotifen and examination of subjective symptoms, blood eosinophil count and serum eosinophil cationic protein (ECP) values were carried out from the pre- to postpollinosis season to evaluate the effects of ECP and characterise the effects of prophylactic treatment on the appearance of these mediators in relation to clinical symptoms. We found that: serum ECP values during the season and post-season were significantly higher than those during the pre-season; there was a significant correlation between serum ECP value and blood eosinophil count during the season; and the levels for all three of the above parameters in the prophylactic treatment group were significantly lower than those in the no-treatment group during the season.

Adult↗