Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lewis rats are prone to T helper (Th) 1 immune responses, whereas Brown Norway (BN) rats are susceptible to Th2 immune responses. Yet, the precise mechanism of induction of the different outcome between these two strains remained elusive. We investigated the expression levels of some cytokines, their receptors and accessory molecules responsible for the polarization of antigen-specific immune response into a predominant Th1 or Th2 profile in Lewis and BN rats. Lymph node (LN) cells collected from rats immunized with short ragweed (RW) were used directly or after stimulation in vitro with RW for 3 days. Expression of cytokines, their receptors and accessory molecules in these LN cells were tested by reverse transcriptase-PCR. Culture supernatant was used for ELISA to detect IL-12 protein. We observed clear differences between these strains in the expression of IL-12p40, which was high in LN cells of Lewis rats even before stimulation in vitro. In addition, a higher amount of IL-12 was present in the culture supernatant in Lewis rats. Upregulation of the expression of IL-12 receptor beta1, beta2, IFN-gamma receptor alpha and beta genes were more prominent in Lewis rats rather than BN rats. Furthermore, attenuated expression of CD40 and CD40 ligand by stimulation in vitro was noted only in BN rats. Changes in expression of these molecules by stimulation as well as higher basal level of IL-12p40 might have led to the activation of Th1 cells in Lewis rats.
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PMID:Mechanism for maintenance of dominant T helper 1 immune responses in Lewis rats. 1147 25

During acute rejection leukocyte-endothelial cell interaction fuelled by costimulatory molecules such as the CD40/CD154 receptor/ligand dyad disrupts microcirculation of the small bowel. Downregulating endothelial CD40 expression by employing a decoy oligonucleotide (dODN) neutralizing the transcription factor signal transducer and activator of transcription-1 (STAT-1) may protect the graft. Therefore allogenic small bowel transplantation was performed in the Brown Norway to Lewis rat model. Graft vessels were pretreated with STAT-1 dODN, mutant control ODN (20 microM) or vehicle (n=8). CD40 antisense ODN and scrambled control ODN-treated transplants served as target control (n=3 each). Intravital microscopy, histology, immunohistochemistry and Western blot analyses were performed 7 days later. Functional capillary density, red blood cell velocity and perfusion index in STAT-1 dODN and CD40 antisense ODN-treated transplants were improved whereas stasis index was reduced. Leukocyte-endothelial cell interaction showed no difference. Histological parameters of rejection, infiltrating CD3-positive cells and apoptotic bodies were also reduced in STAT-1 dODN and CD40 antisense ODN-treated transplants 7 days post-transplantation. CD40 protein abundance was reduced to less than 10% of control in STAT-1 dODN-treated grafts. STAT-1 dODN blockade of CD40 expression improves mucosal perfusion, reduces graft rejection, T-cell infiltration and apoptosis in rat small bowel allografts during acute rejection.
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PMID:STAT-1 decoy oligonucleotide improves microcirculation and reduces acute rejection in allogeneic rat small bowel transplants. 1736 Dec 15

Leukocyte infiltration and activation of the CD40-CD40 ligand costimulatory pathway may promote inflammatory processes such as asthma. The aim of this study was to investigate whether a single intratracheal application of a decoy oligodeoxynucleotide (ODN) specific for signal transducer and activator of transcription (STAT) family members 1 and 3 influences leukocyte influx and pulmonary CD40 expression in a rat model of allergic airway inflammation. In comparison with the corticosteroid budesonide, the authors investigated the efficacy of the STAT decoy ODN in ovalbumin-induced allergic asthma in a Brown Norway rat asthma model. Leukocytes of the bronchoalveolar lavage (BAL) and lung tissue were analyzed and expression of CD40 was assessed by Western blotting. Single administration of the STAT decoy ODN but not of a mutated control ODN or budesonide resulted in a significant decrease of eosinophils and T lymphocytes in the BAL fluid. Cell numbers of CD4+ and CD8+ lymphocytes were significantly decreased in the lung tissue after decoy ODN application. CD40 expression in protein extracts from lung tissue was also reduced significantly following STAT decoy ODN treatment. These findings indicate that a single, local application of a transcription factor decoy ODN specific for STAT1 and STAT3 caused an attenuation of the allergen-induced cellular inflammatory reaction and is at least as effective as a topical steroid.
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PMID:Decoy oligodeoxynucleotide against STAT transcription factors decreases allergic inflammation in a rat asthma model. 2020 94