AWARD NUMBER: W81XWH-13-1-0277 TITLE: A Novel Approach for Effectively Treating SCI Pain, Improving Opioid Efficacy, and Preventing Opioid-Induced Constipation: Key Role of Toll-Like Receptor 4 (TLR4) PRINCIPAL INVESTIGATOR: Dr. Linda Watkins CONTRACTING ORGANIZATION: Regents of the University of Colorado Boulder, CO 80303 REPORT DATE: October 2014 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army...

Toll-like receptors are key to pathogen recognition by a host and to the subsequent triggering of an innate immune response. Experimental and clinical evidence shows that defects in Toll-like receptors or in signaling pathways downstream from these receptors render hosts susceptible to various types of infection, including aspergillosis. Patients receiving an immunosuppressive regimen, includin...

The innate immune system plays an important role in cerebral health and disease. In recent years the role of innate immune regulation by toll-like receptors in the brain has been highlighted. In this paper the expression of toll-like receptors and endogenous toll-like receptor ligands in the brain and their role in cerebral ischemia will be discussed. Further, the ability of systemic toll-like ...

BACKGROUND Toll-like receptors enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharide, viral RNA, CpG-containing DNA and flagellin. Toll-like receptors have also been shown to play a pivotal role in both innate and adaptive immune responses. The role of Toll-like receptors as a primary part of our microbe defense system has bee...

Toll-like receptor 4 (TLR4) is an important pathogen recognition receptor that recognizes mainly lipopolysaccharide (LPS) of Gram-negative bacteria, but also structures from fungal and mycobacterial pathogens, as well as endogenous ligands. Two nonsynonymous polymorphisms of TLR4, Asp299Gly and Thr399Ile, have been suggested to alter the function of the receptor. Some, but not all, studies have...

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conclusions this study suggests that decrease in levels of tlr3 and tlr7 expression is a mechanism that may enable hcv to evade the host innate immune response. results in both groups, we had 13 males and 12 females with a mean age of 48.7 ± 16. tlr3 (6.23 ± 0.91 vs. 3.89 ± 0.85, p < 0.001) and tlr7 (1.48 ± 0.82 vs-1.33 ± 1.18, p < 0.001) expressions were significantly lower in patients with ch...

Toll-like receptors (TLRs) are a primary surveillance system for the detectionof pathogens and are crucial to the activationof host defense. TLR7 and TLR8 sense single-stranded RNA from viruses or host ribonucleoproteins and synthetic imidazoquinolines such as R848, whereas TLR9 senses unmethylated CpG motifs in viral and bacterial DNA and in host DNA. Here we report the endogenous interaction ...

Toll-like receptors (TLRs) are known as pattern-recognition receptors related to the Toll protein of Drosophila. After recognition of pathogen-associated molecular patterns of microbial origin, the TLRs alert the immune system, and initiate innate and adaptive immune responses. The TLR system, though, is not confined solely to the leukocyte-mediated immune defense against exogenous pathogens. B...

Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death globally; treatments that effectively halt progression or reverse the disease, or reduce the occurrence and/or severity of exacerbations, are urgently required [1]. The lack of effective treatments results largely from the incomplete understanding of the mechanisms of pathogenesis of COPD. The pathogenesis of thi...