Differences in the effects of four TRPV1 channel antagonists on lipopolysaccharide-induced cytokine production and COX-2 expression in murine macrophages.
Sepsis is a systemic inflammatory response syndrome triggered by lipopolysaccharide (LPS), an outer membrane component of gram-negative bacteria, and cytokine production via LPS-induced macrophage activation is deeply involved in its pathogenesis. Effective therapy of sepsis has not yet been established. However, it was reported that transient receptor potential vanilloid 1 (TRPV1) channel antagonist capsazepine (CPZ; a capsaicin analogue) attenuates sepsis in a murine model [Ang et al., PLoS ONE 6(9) (2011) e24535; J. Immunol. 187 (2011) 4778-4787]. Here, we profiled the effects of four TRPV1 channel antagonists, AMG9810, SB366791, BCTC and CPZ, on the release of IL-6, IL-1β and IL-18, and on expression of cyclooxygenase 2 (COX-2) in LPS-activated macrophages. Treatment of murine macrophage J774.1 cells or BALB/c mouse-derived intraperitoneal immune cells with LPS induced pro-inflammatory cytokines production and COX-2 expression. Pretreatment with AMG9810 or CPZ significantly suppressed the release of IL-6, IL-1β and IL-18, and COX-2 expression, whereas SB366791 and BCTC were less effective. These results support a role of TRPV1 channel in macrophage activation, but also indicate that only a subset of TRPV1 channel antagonists may be effective in suppressing inflammatory responses. These results suggest that at least some TRPV1 channel antagonists, such as AMG9810 and CPZ, may be candidate anti-inflammatory agents for treatment of sepsis.
Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba, Japan; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
Yuki
Y
Ninomiya
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
Sei-Ichi
SI
Tanuma
Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba, Japan. Electronic address: tsukim@rs.noda.tus.ac.jp.
Mitsutoshi
M
Tsukimoto
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000145:classification; D002460:Cell Line; D002477:Cells; D051546:Cyclooxygenase 2 / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000276:immunology
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
COX-2; Cytokine; Macrophage; Sepsis; TRPV1 channel