ABSTRACT
The cytokine-like hormone leptin is known to exert important functions on the modulation of immune responses. Some of these effects are dependent on the property of leptin to modulate the apoptosis of thymic cells. In the present study, we used Wistar rats to investigate the molecular mechanisms involved in leptin-dependent control of apoptosis in thymus. Apoptosis was evaluated by flow cytometry and ELISA for nucleosome determination, whereas signal transduction was evaluated by immunoprecipitation, immunoblot, and confocal microscopy. The Ob receptor (ObR) was expressed in most thymic cells and its relative amount reduced progressively during thymocyte maturation. ObR expression was colocalized with Janus kinase (JAK)-2 and signal transducer and activator of transcription-3, and an acute, in vivo, injection of leptin promoted the tyrosine phosphorylation of JAK-2 and the engagement of signal transducer and activator of transcription-3. The treatment with leptin also led to the tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and serine phosphorylation of Akt. Chronic treatment with leptin reduced thymic apoptosis, an effect that was not inhibited by the JAK inhibitor AG(490) but was significantly inhibited by the phosphatidylinositol 3-kinase inhibitor LY(294002) and an antisense oligonucleotide to IRS-1. Thus, leptin inhibits the apoptosis of thymic cells through a mechanism that is independent of the activation of JAK-2 but depends on the engagement of the IRS-1/phosphatidylinositol 3-kinase pathway.
Subject(s)
Apoptosis/drug effects , Janus Kinase 2/physiology , Leptin/pharmacology , Phosphatidylinositol 3-Kinases/physiology , Phosphoproteins/physiology , Thymus Gland/drug effects , Animals , Insulin Receptor Substrate Proteins , Leptin/blood , Male , Mice , Mice, Inbred C57BL , Proto-Oncogene Proteins c-akt/physiology , Rats , Rats, Wistar , Receptors, Cell Surface/analysis , Receptors, Leptin , STAT3 Transcription Factor/physiology , Signal Transduction/drug effects , Thymus Gland/cytologyABSTRACT
A penicilina foi o primeiro antibiótico descrito na literatura na década de 1940 e ainda tem o seu papel na medicina moderna. O uso deste medicamento ampliou-se desde sua descrição e atualmente continua a ser a indicação de escolha para algumas doenças. Este trabalho tem como objetivo descrever a importância da penicilina no contexto atual, além de explicitar o mecanismo imunológico de reação adversa às drogas incluindo a alergia à penicilina, mostrando que a reação anafilática é uma situação incomum e freqüentemente diagnosticada pelos médicos e profissionais da área da saúde de forma equivocada. Tal erro leva a uma substituição desta droga, que, apesar de antiga, continua relevante para o tratamento da sífilis.
Penicillin was the first antibiotic described in the literature in the 1940?s, and it still has a role in the modern medicine. The use of this drug has beenamplified since its description, and nowadays, it continues to be the treatment of choice in some diseases. This paper has the objective to describe the importance of penicillin on the actual context, and further, explain the immune mechanisms of adverse reaction to drugs, including penicillin allergy. It is also presented that the anaphylactic reaction is uncommon and it is frequently mistaken diagnosed by doctors and health staff. Such mistake leads to the substitution of this drug, that even described long time ago continues relevant to the treatment of syphilis.
