title: Down-modulation of toll-like receptor 2 expression on granulocytes and suppression of interleukin-8 production due to in vitro treatment with cellulose acetate beads.
abstract: The Adacolumn, which is filled with cellulose acetate beads (CA beads), has been used as a medical device for inflammatory diseases. The CA beads selectively adsorb granulocytes and monocytes and remove them from the peripheral blood. The anti-inflammatory effects of the Adacolumn are possibly caused by removal of these cells but also due to the functional changes in the processed cells. In this study, we investigated the effects of CA beads treatment on modulation of the expression of innate immunity receptors such as the Toll-like receptor (TLR) family and production of an inflammatory cytokine, interleukin-8 (IL-8). Changes in the expressions of TLR1, 2, 4 and 6 in peripheral leukocytes exposed to CA beads were examined by flow cytometry. TLR2 expression on the surface of granulocytes exposed to CA beads was decreased, but the amount of intracellular TLR2 was increased, possibly by internalization. These changes were not observed in monocytes or lymphocytes. Peptidoglycan (PGN) treatment produced similar changes in TLR2 on granulocytes. We also measured the amounts of IL-8 in cultured blood treated with lipopolysaccharide (LPS) and PGN, which are known TLR agonists. PGN-induced IL-8 production was lower in CA beads-treated leukocytes than that in non-treated leukocytes, but LPS did not induce these changes. Based on these findings, we conclude that the down-modulation of TLR2 and suppression of IL-8 production on granulocytes by CA beads, may play an important role in the anti-inflammatory effects of the Adacolumn.
authors: Department of Life Sciences, Faculty of Pharmacy, Yasuda Women's University, 6-13-1Yasuhigashi, Asaminamiku, Hiroshima, Japan. hidaka@yasuda-u.ac.jp
authors: Mayumi
authors: M
authors: Hidaka
authors: Kenji
authors: K
authors: Fukuzawa
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001672:Biocompatible Materials / Q000494:pharmacology*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051193:Toll-Like Receptors / Q000235:genetics; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D016209:Interleukin-8; D010457:Peptidoglycan; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; C005062:acetylcellulose; D002482:Cellulose