Carryover of cigarette smoke effects on hematopoietic cytokines to F1 mouse litters

Abstract

Neutrophils have been implicated in the pathogenesis of COPD, being recruited into the lung in response to cigarette smoke (CS) inhalation and responsible for the release of proteases and oxidant-producing enzymes, resulting in bronchitis and emphysema. Several hematopoietic cytokines are involved in neutrophil growth and recruitment; however, little is known about the effects of CS on hematopoietic cytokines are transmitted between generations. In the present investigation we evaluate the expression of hematopoietic and proinflammatory cytokines in different organs of female F0 mice subjected to sub-chronic CS exposure, and in F1 litters. Virgin female Balb/c mice inhaled either air or air containing CS for 90 days. The specific resistance of the airways (sRaw) was evaluated and, thereafter, the mice were mated with unexposed adult males. The levels of granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF), interleukin-6 (IL-6), IL-1β and TNF-α mRNA and protein were evaluated in the bone marrow, amniotic fluid and bronchoalveolar lavage fluid (BALF) of F0 dams at gestation day14 (gd14) and the bone marrow, BALF and lungs of F0 dams and F1 littermates at post natal day21 (pnd21). At gd14, overexpression of GM-CSF, G-CSF and IL-6 mRNA and protein was observed in the bone marrow, amniotic fluid and BALF of F0 dams. These hematopoietic cytokines were also overexpressed in the lungs of F1 littermates compared with the control F1 litters at pnd21. Lineage-specific hematopoietic growth factors may play an important role in the transmission of neutrophil-associated disease susceptibility across generations.