Abstrait

Docosahexaenoic acid attenuates cell death and interleukin-1beta secretion in THP-1 cells responded to Aggregatibacter actinomycetemcomitans invasion

Aki Kawano, Wataru Ariyoshi, Ryota Yamasaki, Yoshie Yoshioka, Kosuke Kashiwagi, Daisuke Namikawa, Tatsuji Nishihara, Toshinori Okinaga

Macrophages play an important role in the innate immune system by producing inflammatory cytokines in response to substances derived from bacteria and viruses. Recently, omega-3 fatty acids have been shown to have beneficial effects in inflammatory diseases. In this study, we investigated the effects of omega-3 fatty acids on inflammatory responses and cell death induced by the Gram-negative bacterium Aggregatibacter actinomycetemcomitans in macrophages. A. actinomycetemcomitans invasion induced secretion of interleukin (IL)-1β and expression of inflammasome-associated factors, including nucleotide-binding oligomerization domain like receptor protein 3 (NLRP3), adaptor apoptosisassociated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, caspase-4, and cleaved-gasdermin D (GSDMD), in THP-1 cells. Docosahexaenoic acid (DHA), an omega-3 fatty acid suppressed NLRP3, ASC and caspase-1 expression as well as IL-1β secretion by THP-1 cells in response to A. actinomycetemcomitans invasion. Moreover, DHA impaired assembly of ASC, suppressed the expression of caspase-4 and cleaved-GSDMD, and suppressed cell death in A. actinomycetemcomitans-invaded THP-1 cells. Taken together, our data suggest that DHA attenuates the secretion of IL-1β and cell death induced by A. actinomycetemcomitans invasion of macrophages via suppression of inflammasome-associated factors.