Biomedical Research

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.

Author(s): Aki Kawano, Wataru Ariyoshi, Ryota Yamasaki, Yoshie Yoshioka, Kosuke Kashiwagi, Daisuke Namikawa, Tatsuji Nishihara, Toshinori Okinaga
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