Association of TIM-1 5383-5397ins/del and TIM-3 -1541C>T polymorphisms with multiple sclerosis in Isfahan population.

Multiple sclerosis (MS) is an organ-specific autoimmune disease in central nervous system, affecting about 2.5 million people around the world. Probable involvement of two newly identified immunoregulator molecules, TIM-1 and TIM-3, has been reported in autoimmune diseases. In this study, for the first time, the association of TIM-1 5383-5397ins/del and TIM-3 -1541C>T polymorphisms with MS in an Iranian population was considered. The results of our study showed that there is no significant association between TIM-1 5383-5397ins/del and MS (P = 0.38); however, the frequency of CT genotype of TIM-3 -1541C>T in patient group was significantly higher than the control group, and there was a significant association between CT genotype and MS (P = 0.009, OR = 4.08).

Comparison of Helicobacter pylori and Escherichia coli in induction of TNF-alpha mRNA from human peripheral blood mononuclear cells.

PURPOSE: To investigate the difference between the abilities of Helicobacter pylori and Escherichia coli to induce expression of TNF-alpha in human peripheral blood mononuclear cells (PBMC). MATERIALS AND METHODS: H pylori was isolated from gastric biopsy specimens. The mononuclear cells were isolated from human blood, cultured, and treated with either intact or sonicated E coli or H pylori, and mRNA expression for TNF-alpha was detected using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: TNF-alpha mRNA expression levels were significantly higher in PBMCs stimulated with E coli compared to those stimulated with H pylori at the same number and identical conditions (P < .001). The results also suggest that sonicated bacteria were significantly (P < .001) less stimulatory for PBMCs than intact bacteria for both E coli and H pylori. CONCLUSIONS: The ability of different H pylori strains isolated from biopsy samples to stimulate TNF-alpha from PBMCs was significantly lower than that of E coli. Sonicated bacteria, as compared to intact bacteria, was a very poor inducer of TNF-alpha mRNA expression, suggesting that the conformation of lipopolysaccharides (LPS) on the outer leaflet of the outer membrane is not totally conserved in sonicated bacteria.

High-dose leptin activates human leukocytes via receptor expression on monocytes.

Leptin is capable of modulating the immune response. Proinflammatory cytokines induce leptin production, and we now demonstrate that leptin can directly activate the inflammatory response. RNA expression for the leptin receptor (Ob-R) was detectable in human PBMCs. Ob-R expression was examined at the protein level by whole blood flow cytometry using an anti-human Ob-R mAb 9F8. The percentage of cells expressing leptin receptor was 25 +/- 5% for monocytes, 12 +/- 4% for neutrophils, and 5 +/- 1% for lymphocytes (only B lymphocytes). Incubation of resting PBMCs with leptin induced rapid expression of TNF-alpha and IL-6 mRNA and a dose-dependent production of TNF-alpha and IL-6 by monocytes. Incubation of resting PBMCs with high-dose leptin (250 ng/ml, 3-5 days) induced proliferation of resting cultured PBMCs and their secretion of TNF-alpha (5-fold), IL-6 (19-fold), and IFN-gamma (2.5-fold), but had no effect on IL-4 secretion. The effect of leptin was distinct from, and additive to, that seen after exposure to endotoxin or activation by the mixed lymphocyte reaction. In conclusion, Ob-R is expressed on human circulating leukocytes, predominantly on monocytes. At high doses, leptin induces proinflammatory cytokine production by resting human PBMCs and augments the release of these cytokines from activated PBMCs in a pattern compatible with the induction of Th1 cytokines. These results demonstrate that leptin has a direct effect on the generation of an inflammatory response. This is of relevance when considering leptin therapy and may partly explain the relationship among leptin, proinflammatory cytokines, insulin resistance, and obesity.