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Background: Intestinal smooth muscle cells (SMCs) undergo substantial morphological, phenotypic, and contractile changes during inflammatory bowel disease (IBD). SMCs act as a source and target for different inflammatory mediators, however their role in IBD pathogenesis is usually overlooked. Glucagon-like peptide-1 (GLP-1) is an incretin hormone reported to exert multiple anti-inflammatory effects in different tissues including the gastrointestinal tract through various mechanisms. Aim: The aim of this research is to explore the effect of GLP-1 analog exendin-4 on the expression and secretion of inflammatory markers from mouse colon smooth muscle cells (CSMCs) after stimulation with lipopolysaccharide (LPS). Materials and methods: Freshly isolated CSMCs from male BALB/c mice were cultured in DMEM and treated with vehicle, LPS (1 µg/mL), LPS+exendin-4 (50 nM), or LPS+exendin-4 (100 nM) for 24 h. Expression of inflammatory cytokines was then evaluated by antibody array membrane. Results: CSMCs showed basal expression of several cytokines which was enhanced with the induction of inflammation by LPS. However, exendin-4 (50 and 100 nM) significantly (p<0.05) reduced the expression of multiple cytokines including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), T cell activation gene-3 (TCA-3), stromal cell-derived factor-1 (SDF-1), and macrophage colony stimulating factor (M-CSF). To confirm these results, expression of these cytokines was further assessed by enzyme-linked immunosorbent assay and real-time polymerase chain reaction and similar results were also observed. Moreover, secretion of TNF-α and IL1-α into the conditioned media was significantly downregulated by exendin-4 when compared to LPS-treated cells. Furthermore, LPS increased NF-κB phosphorylation, while exendin-4 significantly reduced levels of NF-κB phosphorylation. Conclusion: These data indicate that GLP-1 analogs can exert significant anti-inflammatory effects on CSMCs and can potentially be used as an adjunct treatment for inflammatory bowel conditions. [ABSTRACT FROM AUTHOR]

Objective: Genetic susceptibility to lung cancer is the subject of extensive research. We investigated whether polymorphisms in the microsomal epoxide hydrolase (EPHX1) gene is linked to lung cancer susceptibility in Jordanian patients., Methods: In this case-control study a total of 218 subjects from Jordan University Hospital and King Hussein Cancer Center were screened (108 lung cancer patients and 110 matched controls). Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) was used to detect the two common polymorphisms in EPXH1 located in exons 3 and 4; namely, amino acid substitution from tyrosine to histidine at residue 113 of exon 3 (Tyr113His; low activity allele) and amino acid substitution from histidine to arginine at residue 139 of exon 4 (His139Arg; high activity allele)., Results: There was no significant difference in genotype distribution between control subjects and lung cancer patients. In addition, no differences were found when evaluated according to age, gender or tobacco consumption. For exon 3 the adjusted OR was 0.970 (95% CI 0.473 - 1.991) for the Tyr113/His113 genotype and 0.692 (95% CI 0.301 - 1.590) for the Tyr113/Tyr113 genotype, respectively.  For exon 4 the adjusted OR was 0.596 (95% CI 0.297-1.197) for the His139/Arg139 genotype and 0.882 (95% CI 0.117- 6.660) for the Arg139/Arg139 genotype, respectively. Logistic regression analysis did not show differences in EPXH1 distributions between patients and controls when categorized according to predicted microsomal epoxide hydrolase activity.  Therefore, common polymorphisms within EPHX1 do not appear to be significant risk factors for lung cancer development in the Jordanian population., Conclusion: No associations were observed between lung cancer risk and EPXH1 polymorphisms in the Jordanian population.