https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.22306

Toll-like receptors and adaptor molecules in liver disease: update.

This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of approximately 7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes. These genes display significant variation in expression levels among tissues and are sufficient for discerning tissue-specific expression signatures, indicative of fundamental differences in biochemical processes. In addition, subsets of tissue-selective genes are identified that define key biological processes characterizing each organ. This compendium highlights similarities and differences among organ systems and different individuals and also provides a publicly available resource (Human Gene Expression Index, the HuGE Index, http://www.hugeindex.org) for future studies of pathophysiology.

/pdf/a-compendium-of-gene-expression-in-normal-human-tissues-5b7b1ol4mf.pdf

A compendium of gene expression in normal human tissues.

TLR sense microbial infections, and control activation of immune responses. Dendritic cells, macrophages, and B lymphocytes express TLR and the TLR-signaling adaptor protein MyD88. The impact of TLR-activated B cells on T cell-mediated inflammation is unknown. In this study, we have used mice carrying B cell-restricted deficiencies in MyD88 or in distinct TLR to examine the impact of TLR-activated B cells on a T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis (EAE). We demonstrate that TLR-signaling in B cells suppresses inflammatory T cell responses (both Th1 and Th17), and stimulates recovery from EAE. Only certain TLR are required on B cells for resolution of EAE, and these are dispensable for disease initiation, indicating that a category of TLR agonists preferentially triggers a suppressive function in B cells and thereby limits autoimmune disease. The TLR agonists controlling the regulatory function of B cells are provided by components of Mycobacterium tuberculosis present in the adjuvant. Thus, MyD88 signaling in B cells antagonizes MyD88 signaling in other cells, which drives differentiation of Th17 cells and is required for induction of EAE. Altogether, our data indicate that B cells link recognition of microbial products via TLR to suppression of a T cell-mediated autoimmune disease.

/pdf/tlr-activated-b-cells-suppress-t-cell-mediated-autoimmunity-2z7szdhh1o.pdf

TLR-Activated B Cells Suppress T Cell-Mediated Autoimmunity

Since first being described in the fruit fly Drosophila melanogaster, Toll-like receptors (TLRs) have proven to be of great interest to immunologists and investigators interested in the molecular basis to inflammation. They recognize pathogen-derived factors and also products of inflamed tissue, and trigger signaling pathways that lead to activation of transcription factors such as nuclear factor-κB and the interferon regulatory factors. These in turn lead to induction of immune and inflammatory genes, including such important cytokines as tumor necrosis factor-α and type I interferon. Much evidence points to a role for TLRs in immune and inflammatory diseases and increasingly in cancer. Examples include clear roles for TLR4 in sepsis, rheumatoid arthritis, ischemia/reperfusion injury, and allergy. TLR2 has been implicated in similar pathologic conditions and also in systemic lupus erythematosus (SLE) and tumor metastasis. TLR7 has also been shown to be important in SLE. TLR5 has been shown to be radioprotective. Recent advances in our understanding of signaling pathways activated by TLRs, structural insights into TLRs bound to their ligands and antagonists, and approaches to inhibit TLRs (including antibodies, peptides, and small molecules) are providing possiblemeans by which to interfere with TLRs clinically. Here we review these recent advances and speculate about whether manipulating TLRs is likely to be successful in fighting off different diseases.

/pdf/therapeutic-targeting-of-toll-like-receptors-for-infectious-4u7ahyljh8.pdf

Therapeutic Targeting of Toll-Like Receptors for Infectious and Inflammatory Diseases and Cancer

https://www.gastrojournal.org/article/S0016-5085(06)00065-5/pdf

Toll-like receptor signaling in the liver.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.20839

Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection

Implication of fibrate therapy for homocysteine

dialysis and hemodialysis. Am J Nephrol 1986; 6: 206-11 6 Jackson JM, Lee HA. L-carnitine and acetyl-Lcamitine status during hemodialysis with acetate in humans: a kinetic analysis. Am J Clin Nutr 1996; 64: 922-7 7 Reddi AS, Moquete M, Keshav G, DeAngelis B, Frank 0, Baker H. Plasma carnitine levels in patients undergoing hemodialysis. Nephron 1998; 80: 87-8 8 De Sousa C, English NR, Stacey TE, Chalmers RA. Measurement of L-carnitine and acylcarnitines in body fluids and tissues in children and in adults. Clin Chim Acta 1990; 187: 317-28 9 Takahashi M, Veda S, Misaki H, Sugiyama N, Matsumoto K, Matsuo N, et al. Carnitine determination by an enzymatic cycling method with carnitine dehydrogenase. Clin Chem 1994; 40: 817-21 10 Minkler PE, Hoppel CL. Quantification of free carnitine, individual shortand medium-chain acylcarnitines, and total carnitine in plasma by high-performance liquid chromatography. Anal Biochem 1993; 212: 510-8 II Beutler E, West e. The removal of leukocytes and platelets from whole blood. J Lab Clin Med 1976; 88: 328-33 12 Wanner C, Wackerle B, Boeckle H, Schollmeyer P, Horl WHo Plasma and red blood cell carnitine and carnitine esters during L-carnitine therapy in hemodialysis patients. Am J Clin Nutr 1990; 51: 407-10 13 Zilleruelo G, Novak M, Hsia S, Goldberg R, Abitbol C, Monkus E, et al. Effect of dialysate composition on the lipid response to L-carnitine supplementation. Kidney Int 1989; 27: 259-63 14 Alhomida AS. Influence of acetate and bicarbonate dialysate on blood shortand long-chain acyl carnitine in adult pyelonephritis patients. Ann Clin Biochem 1999; 36: 48-55

https://journals.sagepub.com/doi/pdf/10.1177/000456329903600623

Jean-Pierre Desager

Papers

Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection

Implication of fibrate therapy for homocysteine

Atorvastatin and low-density lipoprotein subfractions profile in mixed hyperlipidaemia: a contributory effect of reduced hepatic lipase activity?