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Keywords:

nitric-oxide production, 15-deoxy-delta(12,14)-prostaglandin j(2), cyclopentenone prostaglandins, hydrogen-peroxide, oxidative stress, cell necrosis, cytokines, iodine, rat, expression, Science & Technology, Life Sciences & Biomedicine, Pathology, NITRIC-OXIDE PRODUCTION, 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2), CYCLOPENTENONE PROSTAGLANDINS, HYDROGEN-PEROXIDE, OXIDATIVE STRESS, CELL NECROSIS, CYTOKINES, IODINE, RAT, EXPRESSION, Acetylcysteine, Animals, Cells, Cultured, Female, Humans, Immunologic Factors, Interferon-gamma, Interleukin-1alpha, Mice, Mice, Inbred NOD, Peroxiredoxins, Prostaglandin D2, Rats, Reactive Oxygen Species, Recombinant Proteins, Thyroid Gland, Thyroiditis, Autoimmune, 11 Medical and Health Sciences, 32 Biomedical and clinical sciences, 42 Health sciences

Abstract:

Reactive oxygen species (ROS) are crucial for thyroid hormonogenesis, and their production is kept under tight control. Oxidative stress (OS) is toxic for thyrocytes in an inflammatory context. In vitro, Th1 pro-inflammatory cytokines have already been shown to decrease thyroid-specific protein expression. In the present study, OS level and its impact on thyroid function were analyzed in vitro in Th1 cytokine (interleukin [IL]-1 alpha/interferon [IFN] gamma)-incubated thyrocytes (rat and human), as well as in vivo in thyroids from nonobese diabetic mice, a model of spontaneous autoimmune thyroiditis. N-acetylcysteine (NAC) and prostaglandin, 15 deoxy-(Delta 12,14)-prostaglandinJ2 (15dPGJ2), were used for their antioxidant and anti-inflammatory properties, respectively. ROS production and OS were increased in IL-1 alpha/IFN gamma-incubated thyrocytes and in destructive thyroiditis. In vitro, NAC not only reduced ROS production below control levels, but further decreased the expression of thyroid-specific proteins in addition to IL-1 alpha/IFN gamma-inhibitory effects. Thus, besides ROS, other intracellular intermediaries likely mediate Th1 cytokine effects. In vivo, NAC and 15dPGJ2 reduced OS and the immune infiltration, thereby leading to a restoration of thyroid morphology. It is therefore likely that NAC and 15dPGJ2 mainly exert their protective effects by acting on infiltrating inflammatory cells rather than directly on thyrocytes. (Am J Pathol 2010, 177:219-228; DOI: 10.2353/ajpath.2010.091253)