17 research outputs found
Innate Immune Activation in Intestinal Homeostasis
Loss of intestinal immune regulation leading to aberrant immune responses to the commensal microbiota are believed to precipitate the chronic inflammation observed in the gastrointestinal tract of patients with inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Innate immune receptors that recognize conserved components derived from the microbiota are widely expressed by both epithelial cells and leucocytes of the gastrointestinal tract and play a key role in host protection from infectious pathogens; yet precisely how pathogenic and commensal microbes are distinguished is not understood. Furthermore, aberrant innate immune activation may also drive intestinal pathology, as patients with IBD exhibit extensive infiltration of innate immune cells to the inflamed intestine, and polymorphisms in many innate immunity genes influence susceptibility to IBD. Thus, a balanced interaction between the microbiota and innate immune activation is required to maintain a healthy mutualistic relationship between the microbiota and the host, which when disturbed can result in intestinal inflammation
THE INTERLEUKIN-6-NEUTRALIZING SOLUBLE (S)IL-6R/SGP130 BUFFER SYSTEM IS DISTURBED IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Leptin receptor expression in Middle Eastern colorectal cancer and its potential clinical implication
We investigated the role of leptin receptor (Ob-R) and its relationship with phosphatidylinositol 3-kinase (PI3K)/AKT activation in colorectal carcinomas (CRCs) tissues followed by in vitro studies using a panel of CRC cell lines. Obesity serves an important risk factor of several cancers including CRC that ranks as the second most common cancer in Saudi Arabia. High levels of adipokine leptin (Ob) and its Ob-R are seen in obesity and also in various carcinomas including CRC. We investigated the proliferative and antiapoptotic effect of Ob on human CRC cell lines Caco-2, HT-29 and SW-840 and the role of PI3K/AKT-signaling pathway in mediating these actions. Then the expression of Ob-R and its relationship with clinicopathological features was analyzed in 448 CRC, 229 normal colon mucosa and 24 colorectal adenomas using tissue microarray technology. Treatment with Ob resulted in increased proliferation of CRC cell lines and involved activation of PI3K/AKT-signaling pathway. Pretreatment with Ob-R small interfering RNA or PI3K inhibitor inhibited these responses. Ob-R was significantly overexpressed in primary CRC relative to adenomas and normal colonic mucosa. In primary CRC, Ob-R significantly correlated with Ob expression, early stage and well-differentiated tumors. Intriguingly, patient with Ob-R positive tumors showed significantly better overall survival ( P  = 0.0098). Ob plays a critical role in CRC carcinogenesis through PI3K/AKT pathway via Ob-R. Ob-R is a prognostic marker associated with better survival