Macrophages play a key role in both normal and pathological processes involving immune and inf lammatory responses, to a large extent through their capacity to secrete a wide range of biologically active molecules. To identify some of these as yet not characterized molecules, we have used a subtraction cloning approach designed to identify genes expressed in association with macrophage activation. One of these genes, designated macrophage inhibitory cytokine 1 (MIC-1), encodes a protein that bears the structural characteristics of a transforming growth factor ␤ (TGF-␤) superfamily cytokine. Although it belongs to this superfamily, it has no strong homology to existing families, indicating that it is a divergent member that may represent the first of a new family within this grouping. Expression of MIC-1 mRNA in monocytoid cells is up-regulated by a variety of stimuli associated with activation, including interleukin 1␤, tumor necrosis factor ␣ (TNF-␣), interleukin 2, and macrophage colony-stimulating factor but not interferon ␥, or lipopolysaccharide (LPS). Its expression is also increased by TGF-␤. Expression of MIC-1 in CHO cells results in the proteolytic cleavage of the propeptide and secretion of a cysteine-rich dimeric protein of M r 25 kDa. Purified recombinant MIC-1 is able to inhibit lipopolysaccharide -induced macrophage TNF-␣ production, suggesting that MIC-1 acts in macrophages as an autocrine regulatory molecule. Its production in response to secreted proinf lammatory cytokines and TGF-␤ may serve to limit the later phases of macrophage activation.

Spermatogenesis, a highly coordinated process, is prone to environmental insults which may lead to impaired spermatogenesis or, at worst, infertility. Bisphenol A (BPA) is a well-known global environmental toxicant and a ubiquitous oestrogenic chemical. This study evaluated the role of selenium (0.5 ppm sodium selenite/kg diet) on spermatogenesis after BPA treatment in different groups of male BALB/c mice: control, selenium, BPA and selenium+BPA. Markers of oxidative stress and apoptosis were evaluated in testis after BPA treatment. Significant decrease in sperm concentration and motility and increased reactive oxygen species(ROS) and LPO levels were seen in BPA group. Histopathological changes revealed extensive vacuolisation, lumen devoid of spermatozoa and decreased germ cell count, confirmed by testicular germ cell count studies. TUNEL assay for apoptosis showed increased number of TUNEL-positive germ cells in BPA group with increased percentage apoptotic index. However, in Se+BPA group, histopathological studies revealed systematic array of all germ cells, preserved basement membrane with relatively less vacuolisation, improved sperm parameters and ROS and LPO levels and decreased number of TUNEL-positive germ cells. These results clearly demonstrate the role of selenium in ameliorating oxidative stress and apoptosis induced upon BPA treatment in mice and can be further used as therapeutic target in male infertility.

No abstract

Labeling studies with 75selenium (75Se) have suggested the existence of selenium-binding proteins in addition to glutathione peroxidase (GSH-Px) in rodent tissues. Three selenium-binding proteins of apparent mol. wt 56, 14 and 12K on SDS-PAGE were isolated from mouse liver using Sephadex G-150 and DEAE-Sephadex chromatography. The proteins were electroeluted from SDS-PAGE gels and injected into rabbits to elicit antibodies. Western immunoblot experiments indicated that the 56K protein was distinct from the 14 and 12K proteins. The latter two proteins appeared to be immunologically related, perhaps as differentially processed variants. The 56 and 14/12K proteins appeared to be distinct from GSH-Px and the 57K plasma selenium-binding proteins. These results indicate that the mouse liver contains at least two selenium-binding proteins distinct from GSH-Px. The existence of the antibodies should permit experiments which help to examine the role of these proteins in the biological function of selenium in mammals.