title: Cutting edge: all-trans retinoic acid down-regulates TLR2 expression and function.
abstract: A major consequence of microbial infection is the tissue injury that results from the host inflammatory response. In acne, inflammation is due in part to the ability of Propionibacterium acnes to activate TLR2. Because all-trans retinoic acid (ATRA) decreases inflammation in acne, we investigated whether it regulates TLR2 expression and function. Treatment of primary human monocytes with ATRA led to the down-regulation of TLR2 as well as its coreceptor CD14, but not TLR1 or TLR4. The ability of a TLR2/1 ligand to trigger monocyte cytokine release was inhibited by pre- and cotreatment with ATRA; however, TLR4 activation was affected by cotreatment only. ATRA also down-regulated monocyte cytokine induction by P. acnes. These data indicate that ATRA exerts an anti-inflammatory effect on monocytes via two pathways, one specifically affecting TLR2/1 and CD14 expression and one independent of TLR expression. Agents that target TLR expression and function represent a novel strategy to treat inflammation in humans.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, USA.
authors.forename: Philip T
authors.initials: PT
authors.lastname: Liu
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Krutzik
authors.forename: Jenny
authors.initials: J
authors.lastname: Kim
authors.forename: Robert L
authors.initials: RL
authors.lastname: Modlin
mesh_terms: D000152:Acne Vulgaris / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology / Q000627:therapeutic use; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D011425:Propionibacterium acnes / Q000276:immunology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014212:Tretinoin