Alginate, a natural polysaccharide, has been widely used in tissue engineering and drug delivery, but like other biomaterials, it causes inflammation by unknown mechanisms. We hypothesized that alginate would stimulate innate immune responses through macrophage receptors. In this study, we showed that sodium alginate induced activation of macrophage-like cells (RAW264.7) through the NF-kappaB pathway. Production of proinflammatory cytokines, such as IL-1beta, IL-6, IL-12, and TNF-alpha was time and dose-dependent. Treatment with alginate solution caused responses that closely paralleled stimulation by lipopolysaccharide in timing and magnitude. These data suggest that sodium alginate causes innate immune responses through NF-kappaB activation and likely activates the same pathways as pathogen recognition.
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