SUMMARYCGN is a rapidly progressive glomerular disease. Monocytes/macrophages are frequently observed in glomeruli in cases of CGN and they are considered to play a crucial role in the pathogenesis of this disease. We described previously the glomerular expression of monocyte chemoattractant protein-1 (MCP-1), which is a potent chemoattractant for monocytes and a member of CC chemokine family, in an experimental model of CGN. In the present study we investigated the expression of mRNAs for other CC chemokines, namely, MCP-3, macrophage inflammatory protein-1a (MIP-1a), MIP-1b, RANTES and TCA3, all of which are chemotactic for monocytes, in the CGN model. First, we established a reverse transcriptase-polymerase chain reaction (RT-PCR) method by which mRNA for each of the CC chemokines could be amplified separately, and then we measured the levels of the expression of mRNAs for the chemokines in diseased glomeruli at several time points after induction of CGN. The mRNAs for all CC chemokines examined were expressed in glomeruli of rats with CGN. Moreover, induction of the gene expression of MIP-1a and MIP-1b seemed to occur earlier than that of the others. CC chemokines may contribute to the recruitment and activation of monocytes in CGN, and each individual CC chemokine may play an overlapping but distinct role in the pathogenesis of this disease.

In this study, the effect of endotoxin tolerance on lipopolysaccharide (LPS)-initiated pulmonary inflammation, the local production of tumour necrosis factor-a (TNF-a) and the cytokine-induced neutrophil attractant (CINC), as well as the activation of nuclear factor-kB (NF-kB) and its subunit composition, were examined in vivo. Endotoxin tolerance was reproduced by four consecutive daily intraperitoneal injections of 0.6 mg/kg of Escherichia coli 055:B5 LPS. Compared with control rats, endotoxin-tolerant rats failed to increase the permeability of pulmonary microvascular or recruit neutrophil to lung tissue upon restimulation with 6 mg/kg of LPSs. Pretreatment with LPSs inhibited the protein level of TNF-a in bronchoalveolar lavage fluid (BALF) and mRNA expression of CINC in lung tissue in response to subsequent LPS stimulation. These changes were accompanied by the suppression of activation of NF-kB, including the low level of total amount of DNA-binding activity and high percentage of non-transactive p50 homodimers. These data demonstrate that endotoxin tolerance can alleviate the LPS-induced acute neutrophilic pulmonary inflammation in rats and can inhibit the proinflammatory cytokines in lung and suggest that endotoxin tolerance might result from the unresponsiveness of NF-kB and persistent high percentage of p50 homodimers. Therefore, the phenomenon of endotoxin tolerance might be used as a strategy for the prevention or treatment of LPS-associated acute respiratory distress syndrome in which excessive or dysregulated inflammation leads to acute lung injury.

SUMMARYLymphotactin (LTN) is the sole member of C chemokine, the third subfamily of chemokines. LTN has been shown to be a chemoattractant specific for CD8 þ cells and/or natural killer (NK) cells, and to be produced by CD8 þ T cells, NK cells, and mast cells. However, there have been no reports describing its expression in clinical or experimental models of diseases so far. Since glomerular infiltration of CD8 þ cells is prominent in an animal model of crescentic glomerulonephritis induced in WKY rats by an injection of anti-glomerular basement membrane antibody, we investigated the gene expression of LTN in this model. LTN mRNA was not detected in normal glomeruli but was detected at 0·5 h after the antibody injection, which detection preceded the infiltration of CD8 þ cells. The expression of LTN mRNA peaked on day 3 and decreased thereafter. We next studied the expression of LTN mRNA in cultured glomerular and vascular cells, and found that glomerular mesangial and vascular endothelial cells could express LTN mRNA when stimulated with IL-1b. These results indicate that the gene expression of LTN is enhanced in the animal model of glomerulonephritis and that intrinsic renal cells are the potential source of the gene expression of LTN in the kidney.

No abstract

Background: Recent studies showed that stress can modulate biological behavior of ovarian carcinoma through adrenergic receptors. Since both nonselective beta-adrenergic receptor antagonist propranolol and selective beta 2-adrenergic receptor (b2AR) antagonist ICI 118,551 instead of b1AR antagonist atenolol could eliminate most of the effects, b2AR is accordingly regarded as the key molecule. In this study, we investigated the role of b2AR in breast cancer. Material and Methods: Gene expression of b2AR was analyzed by RT-PCR in human breast cancer cell lines MDA-MB-231, MDA-MB-435, MDA-MB-468, MCF-7, T47D, BT-549, HCC1937, BCaP-37 and normal mammary epithelial-like cell line HBL-100. b2AR cDNA was transfected into MDA-MB-435 cells. Protein level of b2AR was analyzed by immunohistochemistry in clinical samples, including 25 normal human breast or benign disease breast tissues and 202 breast cancer tissues. Results: b2AR was detected in majority of breast cancer cell lines, except for MDA-MB-435, MCF-7 and T47D, and all of normal or benign disease breast tissues. Both nonselective beta-adrenergic receptor agonist norepinephrine (NE) and selective b2AR agonist terbutaline promoted proliferation and invasion of spontaneous b2AR-positive MDA-MB-231 cells and transfectant MDA-MB-435-b2AR cells, these effects were completely inhibited by selective b2AR antagonist ICI 118,551. In the breast cancer patients, 125 samples (61.9%) expressed b2AR weakly or moderately just as normal breast or benign diseases tissue, and 43 (21.3%) presented significantly stronger b2AR expression, while no b2AR staining was found in other 34 samples (16.8%). Higher expression or lack of b2AR were associated with axillary lymph nodes metastasis and poor disease free survival (DFS). Discussion: Based on our preliminary results, the breast cancer patients could be classified into three subgroups: b2AR “normal”, high expression and negative groups. Overexpression or lack of b2AR associated with metastasis and clinical prognosis in breast cancer. Obviously, abnormal expression of b2AR may influence the outcome of breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4165.