Differences in the effects of four TRPV1 channel antagonists on lipopolysaccharide-induced cytokine production and COX-2 expression in murine macrophages

• Published in: Biochemical and biophysical research communications 2017-03, Vol.484 (3), p.668-674
• Main Authors: Ninomiya, Yuki, Tanuma, Sei-ichi, Tsukimoto, Mitsutoshi
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - classification; Cell Line; Cells; COX-2; Cyclooxygenase 2 - immunology; Cytokine; Cytokines - immunology; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - immunology; Lipopolysaccharides; Macrophage; Macrophage Activation - drug effects; Macrophage Activation - immunology; Macrophages - drug effects; Macrophages - immunology; Macrophages - pathology; Sepsis; TRPV Cation Channels - antagonists & inhibitors; TRPV Cation Channels - immunology; TRPV1 channel
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.01.173

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. •LPS-induced inflammatory responses in macrophages are involved in sepsis.•We examined effect of 4 TRPV1 antagonists on inflammatory responses of macrophages.•AMG9810 and capsazepine significantly suppressed production of IL-6, IL-1β, IL-18.•These antagonists also suppressed LPS-induced expression of COX-2 in macrophages.•Only a subset of TRPV1 channel antagonists may be candidates for sepsis therapy.