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5.1 0.7) (Fig. inflammatory cells, the majority of which were macrophages, as well as higher levels of the Mouse monoclonal to KID macrophage-specific chemokines MCP-1 and CCL9 in whole lung lavage compared TEPP-46 with silica-exposed male mice. We also show that at baseline, estrogen receptor (ER) mRNA expression is lower in female mice than in males and that ER mRNA expression is decreased by silica exposure. Finally, we show that the response of ovariectomized female mice to silica instillation is similar to that of male mice. These observations together show that gender influences the lung response to silica. Keywords:pulmonary diseases accumulating evidence suggeststhat gender can have a profound effect on incidence and severity of a variety of pulmonary diseases (6,7). In children, for example, younger males are more likely to develop asthma (10,46), whereas after puberty, asthma is more common in females (3,10,40,41). The overall incidence and severity of COPD is increasing faster in women than in men (35), which may be related to changing smoking habits over time (12). However, current evidence suggests that women may be more susceptible to the detrimental effects of cigarette smoking than men (9,30,31,54). Epidemiological studies indicate that the incidence of pulmonary fibrosis (PF) is significantly higher in men than in women (25,28,51), whereas mortality rates are increasing more rapidly in women than in men (39). These observations suggest that overall men are more susceptible to PF but that women decline faster once diagnosed. Thus, there is now compelling evidence to suggest that there are gender-based differences in incidence and progression of a variety of lung diseases including PF. In TEPP-46 the developed world, increasingly stringent regulations have reduced occupational exposures to dusts that cause pneumoconiotic lung diseases such as PF (1). However, dust-related lung diseases resulting TEPP-46 from occupational exposures represent a considerable health care cost burden in rapidly industrializing nations (11,34,37). Commonly, the highest exposures to occupational dusts are seen in the least-skilled occupations which, in the developing world, are often filled by women (2,11,36,4749). Thus it is important to understand the biology of gender-based differences to occupational dust exposures. To address the hypothesis that gender contributes to the response to occupational dust exposure, we exposed both male and female C57BL/6 mice to crystalline silica and examined the fibrotic and inflammatory responses. We report here for the first time that the response to silica-induced lung fibrosis is dependent on gender at the silica dose and time point examined. == MATERIALS AND METHODS == == == == Animals. == Eight-week-old C57BL/6 (Jackson Laboratory, Bar Harbor, ME) were given one intratracheal instillation of 0.2 g/kg crystalline silica (a generous gift from Dr. Andy Ghio, Environmental Protection Agency) in 60 l of sterile 0.9% saline or an equivalent volume of 0.9% saline and then killed at 14 days posttreatment. Lungs were lavaged as previously described with 1.5 ml of 0.9% saline (21). All animal procedures were approved by the University of Pittsburgh Institutional Animal Care and Use Committee. == Histological and morphometric analysis. == Lung sections were stained with Masson’s trichrome to visualize collagen. The entire lung was photographed at 20 magnification, and Nikon Elements software was used to calculate tissue volume density (TVD) defined as the percentage of each microscopic field that is lung tissue as well as the percentage of each tissue-containing field that is collagen. Tissue (red) and collagen (blue) staining areas were sampled using six micrographs for each lung as an internal control to account for variability in staining. Values for all fields were TEPP-46 averaged to yield a single TVD per animal. TVD values per animal were then averaged to yield a group average. == Analysis of bronchoalveolar lavage fluid. == Total protein in lavage fluid was determined by Coomassie blue protein assay (Pierce, Rockford, IL) according to the manufacturer’s instructions. A Beckman Z1 TEPP-46 dual Coulter particle counter (Beckman Coulter, Fullerton, CA) was used to obtain total white blood cell counts. White blood cell differentials were determined by light microscopy of Dif Quik-stained (Dade Behring,.