Molecular mechanisms involved in lung inflammatory response induced by LPS in the F2 generation of low birth weight rats

Abstract

It has been demonstrated that adverse environmental factors in prenatal period can disrupt the normal pattern of fetal growth and development, leading to a phenotype more susceptible to diseases, such as hypertension, glucose intolerance, insulin resistance, hyperlipidemia, hyperinsulinemia, obesity, chronic obstructive pulmonary disease, in adulthood. In fact, failure of the maternal-placental supply to match fetal nutrient demand results in a range of fetal adaptations and developmental changes. Although these adaptations may be benecial for short-term survival, they can lead to permanent alterations in body structure and metabolism and thereby to cardiovascular and metabolic diseases in adult life. In previous works, our group demonstrated that global intrauterine undernutrition caused hypocellularity in bone marrow and peripheral blood, in Wistar rats. Besides, the reduction in adhesion molecules expression, in collagen (extracellular matrix), and the generation of inflammatory mediators caused a reduction in leukocyte migration, in these rats. In this model, we also observed reduction in lung allergic inflammation induced by ovalbumin. In lung inflammation leukocytes that migrate to the lung are essential in the induction and resolution of the inflammatory process, but can also be important effectors of tissue damage. The lung inflammation induced by LPS which represents a model of inflammation caused by the activation of toll-like receptors on macrophages. Activation of the cells to become effector lesion involves signaling by a wide range of receptors. It is known that genetic factors could favor the appearance of diseases such as hypertension, obesity and diabetes and that these diseases are intimately related to components of the inflammatory response. Thus, the objective of this study is to evaluate whether the less inflammatory response observed in the offspring of undernourished rats could be perpetuated in the F2 generation and epigenetic changes resulting from global malnutrition throughout the gestation period would be involved in reducing the inflammatory response observed in these animals. (AU)