Aims: This paper investigates the presence of M3 muscarinic acetylcholine receptor autoantibody present in the serum of patients with primary Sj?gren syndrome (pSS). Main methods: We detected the levels of M3mAChR pep...Aims: This paper investigates the presence of M3 muscarinic acetylcholine receptor autoantibody present in the serum of patients with primary Sj?gren syndrome (pSS). Main methods: We detected the levels of M3mAChR peptide IgG, PGE2, IL-1β in serum of SS patients using the enzyme-linked immune sorbent assay (ELISA). To measure the quantity of nitrite/nitrate, we used Griess reagent system. Key findings: Titres of M3mAChR antibody in sera from SS patients are significantly enhanced compared to healthy subjects (control). The enhancement of these autoantibodies is accompanied by the increase of the levels of PGE2, IL-1β and nitrite/nitrate in serum. Under in vitro conditions, the synthetic human M3 peptide impaires the increment of M3mAChR antibody but not that of nati-Ro/SSA antibody. In positive anti-Ro/SSA antibody patients, the increment of M3mAChR peptide IgG and the measured pro-inflammatory substances is related. Significance: On this basis, anti M3mAChR peptide IgG can be said to act as a modulator of the immune system and to play a role in the host-chronic increment of proinflammatory substances in SS patients with positive Ro/SSA antibody. This association between the antibody and the pathogenesis of SS disease may result in useful predicting SS.展开更多
Background: Hypoxia is one of the most frequently encountered stresses in health and disease. Methods: We compared the effects of an anti-β1 periodontal IgG (pIgG) and an authentic β1 adrenergic agonist, xamoterol, ...Background: Hypoxia is one of the most frequently encountered stresses in health and disease. Methods: We compared the effects of an anti-β1 periodontal IgG (pIgG) and an authentic β1 adrenergic agonist, xamoterol, on isolated myocardium from rat atria contractility. We used an ELISA assay to measure the generation of PGE2 in vitro after the addition of either the antibody or the adrenergic agonist. We analyzed the myocardium histopathologically in the presence of both the antibody and/or the adrenergic agonist drug during normoxia, hypoxia and reperfusion conditions. Results: PGE2 generation increased during the hypoxia and was unchanged during reoxygenation period compared with the production of this prostanoid in atria during normoxia condition. A β1 specific adrenoceptor antagonist atenolol and the β1 synthetic peptide abrogated the increment of the prostanoid in the presence of pIgG but only atenolol due to it in the presence of xamoterol. The increment of PGE2 was dependent on the activation of cox-1 and cox-2 isoforms. Moreover, cox-2 was more active and produced more increments in the production of PGE2 in the presence of the pIgG than cox-1 activation. Histopathologically, studies of myocardium specimens during these different periods of the experimental protocol: basal (B), hypoxia (H) and reoxygenation (R), were also performed and showed tissue necrosis and edematization at the myocardium level. Conclusion: The phenomenon studied here supports the notion that PGE2 may be responsible for tissue edematization. PGE2 maybe acts as a beneficial modulator in the myocardium and prevents a major injury of it. The inflammation damage to the heart organ and cardiomyocytes caused by the actions of the antibodies in the course of heart lesions provoked by cardiovascular autoimmune disease, explains some of these results obtained in the present experiments. Further studies will be needed to establish the real role of PGE2 during hypoxia injury of the heart in the course of autoimmune diseases.展开更多
Background: We demonstrated previously that serum IgG from periodontitis patients interacting with the second extracellular loop of the human cardiac β1 adrenoreceptors triggers the production of second messengers. I...Background: We demonstrated previously that serum IgG from periodontitis patients interacting with the second extracellular loop of the human cardiac β1 adrenoreceptors triggers the production of second messengers. In this paper we quantified the production of nitrates/nitrites and nitric oxide (NO), which in turn induces nitric oxide synthase (NOS) mRNA expression. Methods: We determined using β1 IgG, NOS activity isoforms, NOS expression, nitrate/nitrite assay, cGMP accumulation and PKC activity. Results: We established that serum β1 IgG autoantibodies and NO might be considered as early markers in normoxia/hypoxia system in rat isolated atria. The β1 IgG autoantibodies from periodontitis patients, while stimulating myocardial atria β1 adrenoreceptors, exert an increase on NO levels indirectly quantified as nitrite/nitrate, which acts as NO-storage molecules with significant increase in neuronal NOS (nNOS) and inducible NOS (iNOS) mRNA levels in hypoxia conditions. The significant increase in nNOS/iNOS mRNA and NOS activity as well as in NO levels after short-time hypoxia in rat isolated atria was detected. The expression of these genes are related with the increase in atria dF/dt, cyclic GMP (cGMP) and protein kinase C (PKC) activity and resemble the results obtained by Isoproterenol, an β1 adrenoreceptor agonist. Conclusion: These findings indicate that short-term hypoxia up-regulated rat atria NO/NOS system in the presence of β1 IgG autoantibodies shows that an antibody interacting with rat atria β1 adrenoreceptor can act as expression inducer of proinflammatory NO and its metabolites and that it might be useful and helps to maintain heart function and to prevent necrosis and subsequent loss of heart function during hypoxia.展开更多
文摘Aims: This paper investigates the presence of M3 muscarinic acetylcholine receptor autoantibody present in the serum of patients with primary Sj?gren syndrome (pSS). Main methods: We detected the levels of M3mAChR peptide IgG, PGE2, IL-1β in serum of SS patients using the enzyme-linked immune sorbent assay (ELISA). To measure the quantity of nitrite/nitrate, we used Griess reagent system. Key findings: Titres of M3mAChR antibody in sera from SS patients are significantly enhanced compared to healthy subjects (control). The enhancement of these autoantibodies is accompanied by the increase of the levels of PGE2, IL-1β and nitrite/nitrate in serum. Under in vitro conditions, the synthetic human M3 peptide impaires the increment of M3mAChR antibody but not that of nati-Ro/SSA antibody. In positive anti-Ro/SSA antibody patients, the increment of M3mAChR peptide IgG and the measured pro-inflammatory substances is related. Significance: On this basis, anti M3mAChR peptide IgG can be said to act as a modulator of the immune system and to play a role in the host-chronic increment of proinflammatory substances in SS patients with positive Ro/SSA antibody. This association between the antibody and the pathogenesis of SS disease may result in useful predicting SS.
文摘Background: Hypoxia is one of the most frequently encountered stresses in health and disease. Methods: We compared the effects of an anti-β1 periodontal IgG (pIgG) and an authentic β1 adrenergic agonist, xamoterol, on isolated myocardium from rat atria contractility. We used an ELISA assay to measure the generation of PGE2 in vitro after the addition of either the antibody or the adrenergic agonist. We analyzed the myocardium histopathologically in the presence of both the antibody and/or the adrenergic agonist drug during normoxia, hypoxia and reperfusion conditions. Results: PGE2 generation increased during the hypoxia and was unchanged during reoxygenation period compared with the production of this prostanoid in atria during normoxia condition. A β1 specific adrenoceptor antagonist atenolol and the β1 synthetic peptide abrogated the increment of the prostanoid in the presence of pIgG but only atenolol due to it in the presence of xamoterol. The increment of PGE2 was dependent on the activation of cox-1 and cox-2 isoforms. Moreover, cox-2 was more active and produced more increments in the production of PGE2 in the presence of the pIgG than cox-1 activation. Histopathologically, studies of myocardium specimens during these different periods of the experimental protocol: basal (B), hypoxia (H) and reoxygenation (R), were also performed and showed tissue necrosis and edematization at the myocardium level. Conclusion: The phenomenon studied here supports the notion that PGE2 may be responsible for tissue edematization. PGE2 maybe acts as a beneficial modulator in the myocardium and prevents a major injury of it. The inflammation damage to the heart organ and cardiomyocytes caused by the actions of the antibodies in the course of heart lesions provoked by cardiovascular autoimmune disease, explains some of these results obtained in the present experiments. Further studies will be needed to establish the real role of PGE2 during hypoxia injury of the heart in the course of autoimmune diseases.
文摘Background: We demonstrated previously that serum IgG from periodontitis patients interacting with the second extracellular loop of the human cardiac β1 adrenoreceptors triggers the production of second messengers. In this paper we quantified the production of nitrates/nitrites and nitric oxide (NO), which in turn induces nitric oxide synthase (NOS) mRNA expression. Methods: We determined using β1 IgG, NOS activity isoforms, NOS expression, nitrate/nitrite assay, cGMP accumulation and PKC activity. Results: We established that serum β1 IgG autoantibodies and NO might be considered as early markers in normoxia/hypoxia system in rat isolated atria. The β1 IgG autoantibodies from periodontitis patients, while stimulating myocardial atria β1 adrenoreceptors, exert an increase on NO levels indirectly quantified as nitrite/nitrate, which acts as NO-storage molecules with significant increase in neuronal NOS (nNOS) and inducible NOS (iNOS) mRNA levels in hypoxia conditions. The significant increase in nNOS/iNOS mRNA and NOS activity as well as in NO levels after short-time hypoxia in rat isolated atria was detected. The expression of these genes are related with the increase in atria dF/dt, cyclic GMP (cGMP) and protein kinase C (PKC) activity and resemble the results obtained by Isoproterenol, an β1 adrenoreceptor agonist. Conclusion: These findings indicate that short-term hypoxia up-regulated rat atria NO/NOS system in the presence of β1 IgG autoantibodies shows that an antibody interacting with rat atria β1 adrenoreceptor can act as expression inducer of proinflammatory NO and its metabolites and that it might be useful and helps to maintain heart function and to prevent necrosis and subsequent loss of heart function during hypoxia.